Recent Journal Articles: Organic Chemistry -- Neurotransmitter.net

Recent Articles in Natural Product Reports

Liu Y, Wang L, Jung JH, Zhang S
Sesterterpenoids.
Nat Prod Rep. 2007 Dec;24(6):1401-1429.
Covering: 1996 to 2006. [Abstract]

St�ckigt J, Panjikar S
Structural biology in plant natural product biosynthesis-architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis.
Nat Prod Rep. 2007 Dec;24(6):1382-1400.
Covering: 1997 to 2007. [Abstract]

Fraga BM
Natural sesquiterpenoids.
Nat Prod Rep. 2007 Dec;24(6):1350-1381.
Covering: January 2006 to December 2006. [Abstract]

Hanson JR
Steroids: partial synthesis in medicinal chemistry.
Nat Prod Rep. 2007 Dec;24(6):1342-1349.
Covering: January-December 2006. [Abstract]

Hanson JR
Diterpenoids.
Nat Prod Rep. 2007 Dec;24(6):1332-1341.
Covering: January-December 2006. [Abstract]

Abe I
Enzymatic synthesis of cyclic triterpenes.
Nat Prod Rep. 2007 Dec;24(6):1311-1331.
Covering: 2002 to 2006. [Abstract]

Dixon N, Wong LS, Geerlings TH, Micklefield J
Cellular targets of natural products.
Nat Prod Rep. 2007 Dec;24(6):1288-1310.
Covering: 2001 to 2006 inclusive. [Abstract]

Rokem JS, Lantz AE, Nielsen J
Systems biology of antibiotic production by microorganisms.
Nat Prod Rep. 2007 Dec;24(6):1262-1287.
Covering: 1995 to 2006. [Abstract]

Nett M, K�nig GM
The chemistry of gliding bacteria.
Nat Prod Rep. 2007 Dec;24(6):1245-1261.
Covering: up to November 2006. [Abstract]

Baker DD, Chu M, Oza U, Rajgarhia V
The value of natural products to future pharmaceutical discovery.
Nat Prod Rep. 2007 Dec;24(6):1225-1244.
Covering: 2004 to 2006. [Abstract]

Wenzel SC, M�ller R
Myxobacterial natural product assembly lines: fascinating examples of curious biochemistry.
Nat Prod Rep. 2007 Dec;24(6):1211-1224.
Covering: up to April 2007. [Abstract]

Hill RA, Sutherland A
Hot off the press.
Nat Prod Rep. 2007 Dec;24(6):1207-10.
A personal selection of 31 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as trigoxazonane from Trigonella foenum-graecum, which inhibits the germination of seeds of Orobanche crenata. [Abstract]

Gao JM, Wu WJ, Zhang JW, Konishi Y
The dihydro-beta-agarofuran sesquiterpenoids.
Nat Prod Rep. 2007 Oct;24(5):1153-89.
Dihydro-Beta-agarofuran sesquiterpenoids are a structurally diverse class of natural products based on tricyclic 5,11-epoxy-5Beta,10alpha-eudesman-4-(14)-ene skeleton. Between January 1990 and June 2006, 462 new dihydro-Beta-agarofuran sesquiterpenoids of 74 structural types have been isolated from about 64 species of Celastraceae, 3 species of Hippocrateaceae and one species of Lamiaceae. The present review covers the chemical and biological activity research of dihydro-Beta-agarofuran sesquiterpenoids in the past 16 years. The chemical research includes structural classification into sesquiterpene polyesters and macrolide sesquiterpene pyridine alkaloids, synthesis of dihydro-Beta-agarofuran as well as extraction, isolation and purification methods. The biological activity research includes activities such as multidrug resistance (MDR) reversal activity, HIV inhibition, cytotoxicity, antitumor activity, antifeedant activity and insecticidal activity with some insights to their modes of actions. [Abstract]

Saleem M, Ali MS, Hussain S, Jabbar A, Ashraf M, Lee YS
Marine natural products of fungal origin.
Nat Prod Rep. 2007 Oct;24(5):1142-52.
In the search for novel and bioactive molecules for drug discovery, marine-derived natural resources are becoming an important research area. Over 15 marine-derived secondary metabolites are currently in human clinical trials. Terrestrial fungi have produced many therapeutically significant molecules. However, the potential of marine fungi has only been investigated to a limited extent. This review article contains 103 marine-derived fungal metabolites and 77 references. [Abstract]

Daniel JF, Filho ER
Peptaibols of trichoderma.
Nat Prod Rep. 2007 Oct;24(5):1128-41.
The fungal genus Trichoderma has various applications in industry and in medicine, and several species have economic importance as sources of enzymes, antibiotics, plant growth promoters, decomposers of xenobiotics, and as commercial biofungicides. Peptaibiotics and peptaibols are a class of linear peptides synthesized by such fungi, and more than 300 have been described to date. Of this class, those compounds exhibiting antimicrobial activity are referred to as antibiotic peptides. In this review, the biosynthesis, fermentation, structure elucidation (by MS and NMR techniques in particular) and biological activity of antibiotic peptides from Trichoderma species are described. [Abstract]

Buist PH
Exotic biomodification of fatty acids.
Nat Prod Rep. 2007 Oct;24(5):1110-27.
Many biotransformations of mid- to long chain fatty acyl derivatives are intrinsically interesting because of their high selectivity and novel mechanisms. These include one carbon transfer, hydration, isomerization, hydrogenation, ladderane and hydrocarbon formation, thiolation and various oxidative transformations such as epoxidation, hydroxylation and desaturation. In addition, hydroperoxidation of polyunsaturated fatty acids leads to a diverse array of bioactive compounds. The bioorganic aspects of selected reactions will be highlighted in this review; 210 references are cited. [Abstract]

Donadio S, Monciardini P, Sosio M
Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics.
Nat Prod Rep. 2007 Oct;24(5):1073-109.
A total of 223 complete bacterial genomes are analyzed, with 281 citations, for the presence of genes encoding modular polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We report on the distribution of these systems in different bacterial taxa and, whenever known, the metabolites they synthesize. We also highlight, in the different bacterial lineages, the PKS and NRPS genes and, whenever known, the corresponding products. [Abstract]

Smith S, Tsai SC
The type I fatty acid and polyketide synthases: a tale of two megasynthases.
Nat Prod Rep. 2007 Oct;24(5):1041-72.
This review chronicles the synergistic growth of the fields of fatty acid and polyketide synthesis over the last century. In both animal fatty acid synthases and modular polyketide synthases, similar catalytic elements are covalently linked in the same order in megasynthases. Whereas in fatty acid synthases the basic elements of the design remain immutable, guaranteeing the faithful production of saturated fatty acids, in the modular polyketide synthases, the potential of the basic design has been exploited to the full for the elaboration of a wide range of secondary metabolites of extraordinary structural diversity. [Abstract]

Marquet A, Bui BT, Smith AG, Warren MJ
Iron-sulfur proteins as initiators of radical chemistry.
Nat Prod Rep. 2007 Oct;24(5):1027-40.
Iron-sulfur proteins are very versatile biological entities for which many new functions are continuously being unravelled. This review focus on their role in the initiation of radical chemistry, with special emphasis on radical-SAM enzymes, since several members of the family catalyse key steps in the biosynthetic pathways of cofactors such as biotin, lipoate, thiamine, heme and the molybdenum cofactor. It will also include other examples to show the chemical logic which is emerging from the presently available data on this family of enzymes. The common step in all the (quite different) reactions described here is the monoelectronic reductive cleavage of SAM by a reduced [4Fe-4S](1+) cluster, producing methionine and a highly oxidising deoxyadenosyl radical, which can initiate chemically difficult reactions. This set of enzymes, which represent a means to perform oxidation under reductive conditions, are often present in anaerobic organisms. Some other, non-SAM-dependent, radical reactions obeying the same chemical logic are also covered. [Abstract]

Scott DE, Ciulli A, Abell C
Coenzyme biosynthesis: enzyme mechanism, structure and inhibition.
Nat Prod Rep. 2007 Oct;24(5):1009-26.
This review highlights five key reactions in vitamin biosynthesis and in particular focuses on their mechanisms and inhibition and insights from structural studies. Each of the enzymes has the potential to be a target for novel antimicrobial agents. [Abstract]

Webb ME, Marquet A, Mendel RR, R�beill� F, Smith AG
Elucidating biosynthetic pathways for vitamins and cofactors.
Nat Prod Rep. 2007 Oct;24(5):988-1008.
The elucidation of the pathways to the water-soluble vitamins and cofactors has provided many biochemical and chemical challenges. This is a reflection both of their complex chemical nature, and the fact that they are often made in small amounts, making detection of the enzyme activities and intermediates difficult. Here we present an orthogonal review of how these challenges have been overcome using a combination of methods, which are often ingenious. We make particular reference to some recent developments in the study of biotin, pantothenate, folate, pyridoxol, cobalamin, thiamine, riboflavin and molybdopterin biosynthesis. [Abstract]

Holliday GL, Thornton JM, Marquet A, Smith AG, R�beill� F, Mendel R, Schubert HL, Lawrence AD, Warren MJ
Evolution of enzymes and pathways for the biosynthesis of cofactors.
Nat Prod Rep. 2007 Oct;24(5):972-87.
The evolution of metabolic pathways is discussed with reference to the biosynthesis of a number of vitamins and cofactors. Retrograde and patchwork models are highlighted and their relevance to our knowledge of pathway processes and enzymes is examined. Pathway complexity is explained in terms of the acquisition of broad specificity enzymes. [Abstract]

Mendel RR, Smith AG, Marquet A, Warren MJ
Metal and cofactor insertion.
Nat Prod Rep. 2007 Oct;24(5):963-71.
Cells require metal ions as cofactors for the assembly of metalloproteins. Principally one has to distinguish between metal ions that are directly incorporated into their cognate sites on proteins and those metal ions that have to become part of prosthetic groups, cofactors or complexes prior to insertion of theses moieties into target proteins. Molybdenum is only active as part of the molybdenum cofactor, iron can be part of diverse Fe-S clusters or of the heme group, while copper ions are directly delivered to their targets. We will focus in greater detail on molybdenum metabolism because molybdenum metabolism is a good example for demonstrating the role and the network of metals in metabolism: each of the three steps in the pathway of molybdenum cofactor formation depends on a different metal (iron, copper, molybdenum) and also the enzymes finally harbouring the molybdenum cofactor need additional metal-containing groups to function (iron sulfur-clusters, heme-iron). [Abstract]

R�beill� F, Ravanel S, Marquet A, Mendel RR, Smith AG, Warren MJ
Roles of vitamins B5, B8, B9, B12 and molybdenum cofactor at cellular and organismal levels.
Nat Prod Rep. 2007 Oct;24(5):949-62.
Many efforts have been made in recent decades to understand how coenzymes, including vitamins, are synthesised in organisms. In the present review, we describe the most recent findings about the biological roles of five coenzymes: folate (vitamin B9), pantothenate (vitamin B5), cobalamin (vitamin B12), biotin (vitamin B8) and molybdenum cofactor (Moco). In the first part, we will emphasise their biological functions, including the specific roles found in some organisms. In the second part we will present some nutritional aspects and potential strategies to enhance the cofactor contents in organisms of interest. [Abstract]

Weinreb SM
Some recent advances in the synthesis of polycyclic imidazole-containing marine natural products.
Nat Prod Rep. 2007 Oct;24(5):931-48.
This Highlight describes some of the recent synthetic work on imidazole-containing alkaloids isolated from marine sponges. Target molecules have been chosen which demonstrate synthetic strategies leading towards metabolites containing intact imidazole moieties as well as systems bearing modified imidazole rings. [Abstract]

Leeper FJ, Smith AG
Editorial: vitamins and cofactors - chemistry, biochemistry and biology.
Nat Prod Rep. 2007 Oct;24(5):923-6. [Abstract]

Jin Z
Amaryllidaceae and Sceletium alkaloids.
Nat Prod Rep. 2007 Aug;24(4):886-905.
A great number of natural products, especially alkaloids, which exhibit a range of biological activities including acetylcholinesterase inhibition and antineoplastic, cardiovascular and immunostimulatory activities, have been isolated from the plants of the Amaryllidaceae family. this review summarizes isolation, biological activity, and synthetic studies of these alkaloids. The primary biosynthetic pathways of each type of alkaloids are also proposed. [Abstract]

O'Connor PD, Brimble MA
Synthesis of macrocyclic shellfish toxins containing spiroimine moieties.
Nat Prod Rep. 2007 Aug;24(4):869-85.
An overview of the structure and biological activity of macrocyclic polyketides derived from dinoflagellates that contain unusual cyclic imine units is provided. The total and partial syntheses of these molecules are discussed with an emphasis on the construction of the spiroimine functionality thought to be the key pharmacophore of these fact-acting shellfish toxins. [Abstract]

Higuchi K, Kawasaki T
Simple indole alkaloids and those with a nonrearranged monoterpenoid unit.
Nat Prod Rep. 2007 Aug;24(4):843-68.
This review covers the literature on simple indole alkaloids and those with a nonrearranged monoterpenoid unit. Newly isolated alkaloids, structure determinations, total syntheses and biological activities are included. [Abstract]

Schulz S, Dickschat JS
Bacterial volatiles: the smell of small organisms.
Nat Prod Rep. 2007 Aug;24(4):814-42.
This review describes volatiles released into the air by bacteria growing on defined media. Their occurrence, function, and biosynthesis are discussed, and a total of 308 references are cited. An effort has been made to organize the compounds according to their biosynthetic origin. [Abstract]

Recent Articles in Organic Letters

Pathak AK, Yerneni CK, Young Z, Pathak V
Oligomannan Synthesis Using Ionic Liquid Supported Glycosylation.
Org Lett. 2007 Dec 11; .
The synthesis of complex oligosaccharides has been a challenge for researchers. Herein, we describe a strategy for the synthesis of an activated oligomannan 1 that employs ionic liquid (IL) support glycosylation methodology on an IL-tagged mannosyl fluoride donor. This method is capable of rapidly producing linear alpha(1-->6) oligomannan thioglycosides in a convenient and cost-effective manner without the need of column purification after each glycosylation step. [Abstract]

Coldham I, Patel JJ, Raimbault S, Whittaker DT, Adams H, Fang GY, Aggarwal VK
Asymmetric Lithiation-Substitution of Amines Involving Rearrangement of Borates.
Org Lett. 2007 Dec 11;
Asymmetric lithiation of substituted benzylamines, N-Boc-pyrrolidine, or N-Boc-indoline using Beak's methodology was followed by electrophilic quench with trialkylboranes. The resulting borate intermediates rearrange with concomitant C-N bond breakage to give, after oxidation, chiral secondary alcohols with high enantioselectivity. [Abstract]

L�pez CS, P�rez-Balado C, Rodr�guez-Gra�a P, Lera AR
Mechanistic Insights into the Stereocontrolled Synthesis of Hexahydropyrrolo[2,3-b]indoles by Electrophilic Activation of Tryptophan Derivatives.
Org Lett. 2007 Dec 11;
A three-step mechanism involving the formation and rearrangement of an intermediate with indoline-azetidine spirocyclic core structure was shown by DFT computations to account for the electrophilic cyclization of tryptophan derivatives to hexahydropyrrolo[2,3-b]indoles. The corresponding 3a-bromo derivatives have been obtained in high yields and synthetically useful exo/endo ratios. [Abstract]

Matsuda Y, Kitajima M, Takayama H
First Total Synthesis of Trimeric Indole Alkaloid, Psychotrimine.
Org Lett. 2007 Dec 11;
The first total synthesis of (+/-)-psychotrimine, a novel trimeric indole alkaloid isolated from Psychotria rostrata, was achieved. In the total synthesis, the copper-mediated intramolecular and intermolecular aminations of halobenzenes, which respectively contributed to the construction of a pyrrolidinoindoline core and the installation of a third tryptamine unit, were used as key steps. [Abstract]

Esteban J, Costa AM, G�mez A, Vilarrasa J
Michael Addition-Elimination Reactions of Chiral Enolates with Ethyl 3-Halopropenoates.
Org Lett. 2007 Dec 11;
Key dienoic or dienal substructures of cytotoxic macrolides amphidinolide E and dictyostatin have been prepared via a Michael addition (followed by elimination of X-) of chiral enolates on beta-halo derivatives of ethyl acrylate, with full retention of the initial E or Z configuration. Evans oxazolidin-2-ones and our related thiazolidin-2-ones, as well as a fine-tuning of the reaction conditions, have been essential. Many chiral building blocks are accessible from these adducts. [Abstract]

Stoll AH, Knochel P
Preparation of Fully Substituted Anilines for the Synthesis of Functionalized Indoles.
Org Lett. 2007 Dec 11;
A wide range of highly functionalized indoles were prepared by the successive magnesiation of readily available o-alkynyl protected anilines using TMPMgCl.LiCl or LDA, followed by a KH-mediated cyclization reaction. [Abstract]

Zhang X, Xiao Y, Qian X
Highly Efficient Energy Transfer in the Light Harvesting System Composed of Three Kinds of Boron-Dipyrromethene Derivatives.
Org Lett. 2007 Dec 11;
A light-harvesting system containing three kinds of BODIPY fluorophores was synthesized. It exhibited very strong absorption in the region from 300 to 700 nm, and the energy transfer within it was highly efficient. [Abstract]

Tremblay MS, Lee M, Sames D
A Luminescent Sensor for Tyrosine Phosphorylation.
Org Lett. 2007 Dec 11;
We have developed a luminogenic probe for tyrosine phosphorylation based on a short peptide sequence containing an iminodiacetate moiety near the site of phosphorylation. In response to kinase activity, the probe provides a strong luminescence enhancement, resulting from the increased ability of the probe to bind and sensitize Tb3+ and Eu3+ ions upon phosphorylation. [Abstract]

Jung ME, Zhang TH
Anti Aldol Selectivity in a Synthetic Approach to the C(1)-C(12) Fragment of the Tedanolides.
Org Lett. 2007 Dec 8;
In a synthetic approach to the completely protected C1-C12 fragment of the macrocyclic cytotoxic agent tedanolide 1, we carried out the tin-catalyzed Mukaiyama aldol reaction between the 2,3-dialkoxypropanal 5 and the silyl enol ether 6 derived from the ketone 7, which gave, unexpectedly, the anti aldol isomer, rather than the expected syn isomer 4, as the major diastereomer formed. [Abstract]

Hu HY, Xiang JF, Yang Y, Chen CF
A Helix-Turn-Helix Supersecondary Structure Based on Oligo(phenanthroline dicarboxamide)s.
Org Lett. 2007 Dec 8;
An artificial helix-turn-helix (HTH) supersecondary structure based on the oligo(phenanthroline dicarboxamide)s, in which the 2,2'-dimethoxy-1,1'-binaphthyl-6,6'-diamine subunit was utilized as the turn to impart a bias in the twist sense of the supersecondary structure, was reported. The HTH structure has been demonstrated by UV/vis, NMR, CD spectra, and X-ray crystal analysis. [Abstract]

Dunet G, Mayer P, Knochel P
Highly Diastereoselective Addition of Cinnamylzinc Derivatives to alpha-Chiral Carbonyl Compounds.
Org Lett. 2007 Dec 8;
Cinnamylzinc reagents react with cyclic and acyclic alpha-chiral ketones under very mild conditions (-78 degrees C, 1 h), yielding the corresponding homoallylic alcohols bearing three adjacent stereocenters with high diastereoselectivity. An extension of this reaction to enantioenriched alpha-chiral ketones is also described. [Abstract]

Schmidt B, Biernat A
Tandem RCM-Isomerization Approach to Glycals of Desoxyheptoses from a Common Precursor.
Org Lett. 2007 Dec 8;
Ring closing metathesis and tandem RCM-isomerization have been applied to the synthesis of six- to eight-membered oxacycles, starting from a common precursor. The products of the tandem RCM-isomerization sequence are glycals of 3-deoxyheptoses of varying ring size. [Abstract]

Marois JS, Cantin K, Desmarais A, Morin JF
[3]Rotaxane-Porphyrin Conjugate as a Novel Supramolecular Host for Fullerenes.
Org Lett. 2007 Dec 8;
A new supramolecular host with good affinity toward fullerenes has been developed. This host having a tweezer-like shape is built on a [3]rotaxane scaffold and contains two free-base porphyrin moieties as recognition units for fullerenes. The ability of this tweezer to bind fullerenes strongly depends on the solvent system used and the size of fullerene. [Abstract]

Waetzig JD, Hanson PR
A Multifaceted Phosphate Tether: Application to the C1-C14 Subunit of Dolabelides A-D.
Org Lett. 2007 Dec 7;
A phosphate tether approach to the C1-14 subunit of dolabelide is described. The phosphate tether serves a multifaceted role mediating several processes, including (i) diastereotopic differentiation via RCM, (ii) selective CM by imparting Type III behavior to the exocyclic olefin, (iii) regioselective hydrogenation, and (iv) regioselective Pd(0)-catalyzed reductive opening of the bicyclic phosphate. Overall, this strategy uses orthogonal protecting- and leaving-group properties innate to phosphate esters to rapidly assembly the titled subunit. [Abstract]

Bouffard J, Kim Y, Swager TM, Weissleder R, Hilderbrand SA
A Highly Selective Fluorescent Probe for Thiol Bioimaging.
Org Lett. 2007 Dec 7;
A new fluorescent turn-on probe (3) for the selective sensing and bioimaging of thiols is reported. In aqueous buffer solutions at physiological pH, thiols cleave the 2,4-dinitrobenzenesulfonyl group to release the red-emissive donor-acceptor fluorophore (4). The probe displays excellent immunity to interference from nitrogen and oxygen nucleophiles and the imaging of thiols in living cells is demonstrated. [Abstract]

Nelson HM, Stoltz BM
Progress toward the Synthesis of the Basiliolides and Transtaganolides: An Intramolecular Pyrone Diels-Alder Entry into a Novel Class of Natural Products.
Org Lett. 2007 Dec 7;
Efforts directed toward the synthesis of a basiliolide/transtaganolide model system are disclosed. A highly endo-selective intramolecular pyrone Diels-Alder (IMPDA) cycloaddition rapidly constructs the tricyclic core of the basiliolides and transtaganolides. [Abstract]

Burns AC, Forsyth CJ
Intramolecular Diels-Alder/Tsuji Allylation Assembly of the Functionalized trans-Decalin of Salvinorin A.
Org Lett. 2007 Dec 7;
An enantioselective synthesis of the highly functionalized trans-decalin core (2) of salvinorin A is described. The tetraene 4 was synthesized in six steps from a known l-(+)-tartaric acid derivative. Three contiguous stereocenters, two of them quaternary, on the trans-decalin were established asymmetrically by an intramolecular Diels-Alder/Tsuji allylation sequence. [Abstract]

Cui SL, Wang J, Wang YG
Facile Access to Pyrazolines via Domino Reaction of the Huisgen Zwitterions with Aziridines.
Org Lett. 2007 Dec 7;
A novel, efficient, and general domino reaction of 2-acylaziridines with the Huisgen zwitterions to furnish 2-pyrazoline rings is described. A possible mechanism for the domino sequence is proposed. [Abstract]

Lee SS, Kim HS, Hwang TK, Oh YH, Park SW, Lee S, Lee BS, Chi DY
Efficiency of Bulky Protic Solvent for S(N)2 Reaction.
Org Lett. 2007 Dec 6;
We calculate and compare the effects of aprotic vs protic solvent on the rate of SN2 reaction [F- + C3H7OMs--> C3H7F + OMs-]. We find that aprotic solvent acetonitrile is more efficient than a small protic solvent such as methanol. Bulky protic solvent (tert-butyl alcohol) is predicted to be quite efficient, giving the rate constant that is similar to that in CH3CN. Our calculated relative activation barriers of the SN2 reaction in methanol, tert-butyl alcohol, and CH3CN are in good agreement with experimental observations. [Abstract]

Wang JL, Tang ZM, Xiao Q, Zhou QF, Ma Y, Pei J
Molecular Wires Based on Thienylethynylene: Synthesis, Photophysical Properties, and Excited-State Lifetime.
Org Lett. 2007 Dec 6;
A series of pi-conjugated molecular wires based on thienylethynylene units have been developed to understand the effect of the molecular structures on their photophysical properties. The investigation of their photophysical properties indicates that the formation of aggregates at the ground state is effectively suppressed by the incorporation of truxene units. The excited-state lifetimes are observed to be biexponential for these molecular wires. [Abstract]

Sessler JL, Cho DG
The Benzil Rearrangement Reaction: Trapping of a Hitherto Minor Product and Its Application to the Development of a Selective Cyanide Anion Indicator.
Org Lett. 2007 Dec 5;
The isolation and characterization of an intermediate from the benzil-cyanide reaction is reported. The use of this trapping chemistry to produce a chemical indicator for the cyanide anion is described. It relies on the synthesis and reaction of a pi-extended analogue of benzil. Addition of tetrabutylammonium cyanide to organic solutions of this species, referred to as compound 3 in the text, gives rise to a dramatic change in both color and fluorescence properties. [Abstract]

Lee KS, Kim HJ, Kim GH, Shin I, Hong JI
Fluorescent Chemodosimeter for Selective Detection of Cyanide in Water.
Org Lett. 2007 Dec 5;
A coumarin-based fluorescent chemodosimeter with a salicylaldehyde functionality as a binding site has been developed for selective detection of cyanide anions over other anions in water at biological pH. [Abstract]

Zapata F, Caballero A, Espinosa A, Tarraga A, Molina P
Triple Channel Sensing of Pb(II) Ions by a Simple Multiresponsive Ferrocene Receptor Having a 1-Deazapurine Backbone.
Org Lett. 2007 Dec 5;
A new redox, chromogenic, and fluorescent chemosensor molecule based on a deazapurine ring selectively senses aqueous Pb2+ in acetonitrile over other metal ions examined: redox shift (DeltaE1/2 = 0.15 V of the Fe(II)/Fe(III) redox couple), the colorless to orange color change, and an emission change of 620-fold, with an unprecedented detection limit of 2.7 mug L-1. The signal transduction occurs via a reversible CHEF with this inherent quenching metal ion. [Abstract]

Marshall JA, Eidam PM
A Formal Synthesis of the Callipeltoside Aglycone.
Org Lett. 2007 Dec 5;
A synthesis of the macrocyclic core structure of callipeltoside A and a C9 epimer has been achieved by applications of chiral vinylzinc or Kishi-Nozaki-Hiyama (K-N-H) additions, Roskamp homologations, and acylketene or intramolecular K-N-H macrolactonizations as key bond-forming steps. [Abstract]

Simsek S, Horzella M, Kalesse M
Oxazaborolidinone-Promoted Vinylogous Mukaiyama Aldol Reactions.
Org Lett. 2007 Dec 4;
delta-Hydroxy-alpha,beta-unsaturated carbonyl compounds were prepared in one step via the vinylogous Mukaiyama aldol reactions with O,O-silyl ketene acetals. Isopropyl alcohol as additive and tryptophane-based B-phenyloxazaborolidinone were required for obtaining the gamma-alkylated product in high enantioselectivities. [Abstract]

Chou HH, Wu HM, Wu JD, Ly TW, Jan NW, Shia KS, Liu HJ
Polyene Cyclization Promoted by the Cross-Conjugated alpha-Carbalkoxy Enone System. Observation on a Putative 1,5-Hydride/1,3-Alkyl Shift under Lewis Acid Catalysis.
Org Lett. 2007 Dec 4;
Polyene cyclization of compounds 3 and 4 under catalysis with AlCl3 and/or SnCl4 gave rise to complex bicyclic products 8 and 9, structures of which were highly unexpected, and X-ray analyses were invoked for unambiguously structural identification. Mechanistically, a tandem sigma-bond rearrangement process, including an unusual through-space 1,5-hydride or 1,3-alkyl shift as a key operation, is proposed. [Abstract]

Siebert MR, Yudin AK, Tantillo DJ
Cycloaddition/Ring Opening Reaction Sequences of N-Alkenyl Aziridines: Influence of the Aziridine Nitrogen on Stereoselectivity.
Org Lett. 2007 Dec 4;
The cycloaddition of (Z)-7-(prop-1-enyl)-7-azabicyclo[4.1.0]heptane with dimethyl acetylene dicarboxylate (DMAD) was reported previously to proceed with complete stereoselectivity. Quantum chemical calculations (B3LYP) were used to evaluate the mechanism of the cyclization process, and it was discovered that a stepwise pathway is preferred. The subsequent electrocyclic ring opening reaction of the cyclobutene was also studied, and it was found that ring opening to the "methyl-in" dienamine is preferred to the "methyl-out" product by some 4-5 kcal/mol. [Abstract]

Magens S, Ertelt M, Jatsch A, Plietker B
A Nucleophilic Fe Catalyst for Transesterifications under Neutral Conditions.
Org Lett. 2007 Dec 4;
Carboxylic esters belong to the most important functional groups in organic chemistry. Strong efforts have been made in developing mild catalytic procedures for their preparation. Among the various methods developed to date, transesterifications have occupied an important space. In the present paper, a new catalytic method for this process based on the use of nucleophilic Fe(-II) complexes is presented. Evidence for the formation of an intermediate acyl Fe complex will be presented as well as investigations on scope and limitations. [Abstract]

Toueg J, Prunet J
Dramatic Solvent Effect on the Diastereoselectivity of Michael Addition: Study toward the Synthesis of the ABC Ring System of Hexacyclinic Acid.
Org Lett. 2007 Dec 4;
During our studies toward the synthesis of the ABC ring system of hexacyclinic acid, we have observed a dramatic influence of the solvent on both our key steps. The diastereoselectivity of the intermolecular Michael addition could be totally reversed by changing the polarity of the solvent, and trifluoroethanol was found to be the optimal solvent for the following Mn(III)-promoted radical cyclization. [Abstract]

Yamashita F, Kuniyasu H, Terao J, Kambe N
Platinum-Catalyzed Regio- and Stereoselective Arylthiolation of Internal Alkynes.
Org Lett. 2007 Dec 4;
Unsymmetrical internal alkynes such as ethyl phenylpropiolate (2b) successfully underwent Pt-catalyzed decarbonylative arylthiolation by thioesters. The regio- and stereoselective insertion of 2b into an S-Pt bond was confirmed by reaction with a platinum complex with an S-Pt-Cl framework. [Abstract]

Recent Articles in The Journal of Organic Chemistry

Cornel VM
Number 87.
J Org Chem. 2007 Dec 11; .
Reviews are listed in order of appearance in the sources indicated. In multidisciplinary review journals, only those reviews which fall within the scope of this Journal are included. Sources are listed alphabetically in three categories: regularly issued review journals and series volumes, contributed volumes, and other monographs. Titles are numbered serially, and these numbers are used for reference in the index. Major English-language sources of critical reviews are covered. Encyclopedic treatises, annual surveys such as Specialist Periodical Reports, and compilations of symposia proceedings are omitted. This installment of Recent Reviews covers principally the middle part of the 2007 literature. Previous installment: J. Org. Chem. 2007, 72(20), 7809-16. [Abstract]

Avirah RR, Jyothish K, Ramaiah D
Infrared Absorbing Croconaine Dyes: Synthesis and Metal Ion Binding Properties.
J Org Chem. 2007 Dec 11;
Quinaldine-based croconaine dyes synthesized by the condensation reaction between croconic acid and the respective quinaldinium salts are described. These dyes exhibit absorption maximum in the infrared region (840-870 nm) with high molar extinction coefficients (1-5 x 105 M-1 cm-1) and have very low fluorescence quantum yields. Upon binding to divalent metal ions, these dyes were found to form complexes with a 2:1 stoichiometry having high association constants of the order of 1011-1014 M-2, while the monovalent metal ions showed negligible affinity. The binding of the croconaine dye 3d with divalent metal ions especially Zn2+, Pb2+, and Cd2+ led to significant chelation-enhanced fluorescence emission. The broadening of the aromatic signals, vinylic and N-methyl protons and the negligible changes at the aliphatic region of the dye 3d in the 1H NMR spectrum in the presence of Zn2+, indicate that the binding occurs at the carbonyl groups of the croconyl ring. The shift in the croconyl carbonyl stretching frequency in the [3d-Zn2+] complex analyzed through FT-IR analysis further confirms the involvement of two electron-rich carbonyl groups of the croconyl moiety in the complexation. These results demonstrate that the binding of the divalent metal ions at the carbonyl oxygens of these infrared absorbing dyes can be favorably utilized for the development of potential sensors for the detection of metal ions and further can be exploited as sensitizers for photodynamic therapeutic applications. [Abstract]

Fenster E, Smith BT, Gracias V, Milligan GL, Aub� J
Nucleophilic Addition to Iminium Ethers in the Preparation of Functionalized N-Alkyl Heterocycles.
J Org Chem. 2007 Dec 11;
Bicyclic iminium ethers can be synthesized by the reactions of ketones with hydroxyalkyl azides. These cationic species react with a variety of nucleophiles via two possible pathways. The initially formed, kinetic product arises from direct addition to the iminium carbon in the substrate. In some cases, the initial adduct reverts to the starting iminium ether and the ultimate product arises from nucleophilic displacement at the O-alkyl group to afford the terminally functionalized N-substituted amide. The behavior of a range of nucleophiles was studied by using several iminium ethers. In general, the relevant pathway could be identified by characterization of the product formed. For hydroxide addition, which can afford only one product regardless of mechanism, the reaction was shown to arise by the kinetic pathway, using 18O-labeled hydroxide. A one-pot synthesis of functionalized lactams entailing treatment of ketones first with hydroxyalkyl azides followed by nucleophilic addition was also developed. [Abstract]

Chen P, Wang J, Liu K, Li C
Synthesis and Structural Revision of (+/-)-Laurentristich-4-ol.
J Org Chem. 2007 Dec 11;
The structure of tetracyclic natural sesquiterpene laurentristich-4-ol was revised based on its synthetic studies. The proposed and the revised structures of laurentristich-4-ol were both synthesized with SmI2-mediated ketyl radical cyclization as the key step to construct the spirocyclic ether skeleton. [Abstract]

Valiulin RA, Kutateladze AG
2,6,7-Trithiabicyclo[2.2.2]octanes as Promising Photolabile Tags for Combinatorial Encoding.
J Org Chem. 2007 Dec 11;
The adducts of trithiabicyclo[2.2.2]octane (TTBO) and carbonyl compounds undergo efficient photoinduced fragmentation with quantum yields comparable to that of dithiane adducts. The effect of the third sulfur on the stability of the respective radical cations and radicals is examined computationally and experimentally in a laser flash photolysis study. A straightforward synthetic approach to a variety of 4-substituted trithiabicyclo[2.2.2]octanes from 3-bromo-2,2-bis(bromomethyl)propanol is developed, making a diverse set of mass-differentiated photolabile tags readily available for combinatorial encoding. [Abstract]

Ollevier T, Bouchard JE, Desyroy V
Diastereoselective Mukaiyama Aldol Reaction of 2-(Trimethylsilyloxy)furan Catalyzed by Bismuth Triflate.
J Org Chem. 2007 Dec 11;
We have developed an efficient vinylogous Mukaiyama aldol reaction of 2-(trimethylsilyloxy)furan with various aromatic aldehydes mediated by bismuth triflate in low catalyst loading (1 mol %). The reaction proceeds rapidly and affords the corresponding 5-(hydroxy(aryl)methyl)furan-2(5H)-ones in high yields with good to very good diastereoselectivities (dr up to >98:2). Such selectivities, albeit previously reported with other Lewis acids, could this time be achieved with a much lower catalyst loading. 5-(Hydroxy(alkyl)methyl)furan-2(5H)-ones derived from ketones could also be obtained with good diastereoselectivities. [Abstract]

Punidha S, Sinha J, Kumar A, Ravikanth M
First Triazole-Bridged Unsymmetrical Porphyrin Dyad via Click Chemistry.
J Org Chem. 2007 Dec 11;
Click chemistry has been successfully applied in the synthesis of the first example of a triazole-bridged porphyrin dyad containing N2S2 porphyrin and N4 or ZnN4 porphyrin subunits, and fluorescence study indicated a possibility of singlet-singlet energy transfer from the N4 or ZnN4 porphyrin subunit to the N2S2 porphyrin subunit. [Abstract]

Goh YW, Pool BR, White JM
Structural Studies on Cycloadducts of Furan, 2-Methoxyfuran, and 5-Trimethylsilylcyclopentadiene with Maleic Anhydride and N-Methylmaleimide.
J Org Chem. 2007 Dec 11;
The early stages of the retro-Diels-Alder reaction are clearly apparent in the structures of the cycloadducts formed between furan or 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide. The degree of lengthening of the C-C bonds that break in this reaction is clearly related to the known reactivity of these cycloadducts toward this reaction. In the structures of the cycloadducts 21 and 22 derived from 2-methoxyfuran, the early stages of an alternative fragmentation reaction are apparent, consistent with the reactivity of these compounds in solution. [Abstract]

Bronstein HE, Scott LT
Fullerene-like Chemistry at the Interior Carbon Atoms of an Alkene-Centered C(26)H(12) Geodesic Polyarene(1).
J Org Chem. 2007 Dec 11;
The title compound (1) undergoes 1,2-addition reactions of both electrophilic and nucleophilic reagents preferentially at the "interior" carbon atoms of the central 6:6-bond to give fullerene-type adducts 2, 3, 4, and 5. Such fullerene-like chemistry is unprecedented for a topologically 2-dimensional polycyclic aromatic hydrocarbon and qualifies this geodesic polyarene as a "bridge" between the old flat world of polycyclic aromatic hydrocarbons (PAHs) and the new round world of fullerenes. The relief of pyramidalization strain, as in the addition reactions of fullerenes, presumably contributes to the atypical mode of reactivity seen in 1. Molecular orbital calculations, however, reveal features of the nonalternant pi system in 1 that may also play an important role. Thus, the fullerene-like chemistry of 1 may be driven by two or more factors, the relative importances of which are difficult to discern. [Abstract]

Tsuchiya T, Okada Y, Shimizu T, Hirabayashi K, Kamigata N
Molecular Transformations of Unsaturated Thiacrown Ethers.
J Org Chem. 2007 Dec 11;
Unsaturated thiacrown ethers with 15, 18, and 21 members were oxidized to sulfoxides by the reaction with m-CPBA. The reaction with t-BuOCl at -20 degrees C also afforded sulfoxides, whereas the reaction at room temperature yielded cis-trans isomerized compounds. The cis-trans isomerized compound was also obtained by the photochemical reaction or by the reaction with NCS and NCP. Meanwhile, the reaction with NBS and NBP provided an acetal via 1,2-bridged bromonium intermediate. [Abstract]

Hao W, Parker VD
Rapid Formation and Slow Collapse of a Carbocation-Anion Pair to a Neutral Molecule.
J Org Chem. 2007 Dec 8;
The 4,4',4' '-trimethoxytrityl cation (TMT+) was observed to react with acetate ion in acetic acid reversibly to give the corresponding ester (TMT-OAc). The rate of the reaction was found to be independent of [NaOAc] over a 25000-fold range. Similar results were observed in the presence of Bu4N+ in acetic acid as well as in HOAc/AN (1/1). It was concluded that {TMT+ (HOAc/AcO-)} is an ion pair that forms essentially completely from free TMT+ and HOAc/AcO- during the time of mixing under stopped-flow conditions. The process which was studied kinetically is the intramolecular collapse of the ion pair to TMT-OAc which takes place in two steps involving a kinetically significant intermediate. The remarkably close resemblance of this reaction to the Winstein scheme for solvolysis reactions is noted. In analogy to the Winstein scheme, it was proposed that the intermediate could be an intimate ion pair formed upon extrusion of solvent from the solvent separated ion pair. The product-forming step could then correspond to the intimate ion pair reacting further to form a covalent bond between the two moieties within the complex. The values of the thermodynamic and the activation parameters as well as the apparent rate constants for the reaction in the presence of either sodium or tetrabutylammonium ions suggest that these counterions play insignificant roles in the reactions. However, the equilibrium constant for the intramolecular step (K4) was observed to be two times greater in the presence of Bu4N+ than in the presence of Na+. The rate of the reaction in HOAc was observed to be about four times as great as that in HOAc/AN (1/1). [Abstract]

Lietard J, Meyer A, Vasseur JJ, Morvan F
New Strategies for Cyclization and Bicyclization of Oligonucleotides by Click Chemistry Assisted by Microwaves.
J Org Chem. 2007 Dec 8;
The synthesis of cyclic, branched, and bicyclic oligonucleotides was performed by copper-catalyzed azide-alkyne cycloaddition assisted by microwaves in solution and on solid support. For that purpose, new phosphoramidite building blocks and new solid supports were designed to introduce alkyne and bromo functions into the same oligonucleotide by solid-phase synthesis on a DNA synthesizer. The bromine atom was then substituted by sodium azide to yield azide oligonucleotides. Cyclizations were found to be more efficient in solution than on solid support. This method allowed the efficient preparation of cyclic (6- to 20-mers), branched (with one or two dangling sequences), and bicyclic (2 x 10-mers) oligonucleotides. [Abstract]

Liu Z, Shi F, Martinez PD, Raminelli C, Larock RC
Synthesis of Indazoles by the [3+2] Cycloaddition of Diazo Compounds with Arynes and Subsequent Acyl Migration.
J Org Chem. 2007 Dec 8;
The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively. [Abstract]

Keith JM
One Step Conversion of Heteroaromatic-N-Oxides to Imidazolo-Heteroarenes.
J Org Chem. 2007 Dec 8;
Various pyridine-, quinoline-, isoquinoline-, and pyrimidine-N-oxides were converted to their corresponding alpha-imidazoloheteroarenes in good yield by treatment with sulfuryl diimidazole in nonpolar solvents at elevated temperatures. [Abstract]

Hubbard A, Okazaki T, Laali KK
Halo- and Azidodediazoniation of Arenediazonium Tetrafluoroborates with Trimethylsilyl Halides and Trimethylsilyl Azide and Sandmeyer-Type Bromodediazoniation with Cu(I)Br in [BMIM][PF(6)] Ionic Liquid.
J Org Chem. 2007 Dec 8;
Reaction of [ArN2][BF4] salts immobilized in [BMIM][PF6] ionic liquid (IL) with TMSX (X = I, Br) and TMSN3 represents an efficient method for the preparation of iodo-, bromo-, and azido-derivatives via dediazoniation. The reactions can also be effected starting with ArNH2 by in situ diazotization with [NO][BF4] followed by reaction with TMSX or TMSN3. Depending on the substituents on the benzenediazonium cation, competing fluorodediazoniation (ArF formation) and hydrodediazoniation (ArH formation) were observed. Dediazoniation with TMSN3 and with TMSI generally gave the highest chemoselectivity toward ArN3 and ArI formation. The IL was recycled and reused up to 5 times with no appreciable decrease in the conversions. Multinuclear NMR monitoring of the interaction of [ArN2][BF4]/TMSX, [BMIM][PF6]/TMSX, and [BMIM][PF6]/TMSX/[ArN2][BF4] indicated that TMSF is formed primarily via [ArN2][BF4]/TMSX, generating [ArN2][X] in situ, which gives ArX on dediazoniation. Competing formation of ArF in Sandmeyer-type bromodediazoniation of [ArN2][BF4] with Cu(I)Br immobilized in the IL points to significant involvement of heterolytic dediazoniation. [Abstract]

Xue J, Liu P, Pan Y, Guo Z
A Total Synthesis of OSW-1.
J Org Chem. 2007 Dec 8;
A new and practical method was developed to synthesize OSW-1, a natural saponin with potent antitumor activities, from (+)-dehydroisoandrosterone, l-arabinose, and d-xylose on gram scale. The synthesis was achieved in 10 linear steps with an overall yield of 6.4% starting from (+)-dehydroisoandrosterone. [Abstract]

Cernak TA, Gleason JL
Density Functional Theory Guided Design of Exo-Selective Dehydroalanine Dienophiles for Application Toward the Synthesis of Palau'amine.
J Org Chem. 2007 Dec 8;
Diels-Alder cycloadditions of dehydroalanine derivatives with cyclopentadiene, applicable to the synthesis of palau'amine, were investigated experimentally and using DFT computations at the B3LYP/6-31G* level of theory. Oxazolone and thiohydantoin dienophiles were found to be significantly more reactive than hydantoins or dehydroalanine methyl esters. The increased reactivity of the thiohydantoins relative to hydantoins is attributed to increased conjugation of nitrogen lone pairs into the thiocarbonyl group. beta-Substitution greatly decelerates the cycloadditions due to steric interactions in the transition states outweighing any electronic activation by chlorine. Hydantoins and thiohydantoins were found to be exo-selective, while the corresponding oxazolones and dehydroalanines were unselective. [Abstract]

Phan L, Andreatta JR, Horvey LK, Edie CF, Luco AL, Mirchandani A, Darensbourg DJ, Jessop PG
Switchable-Polarity Solvents Prepared with a Single Liquid Component.
J Org Chem. 2007 Dec 8;
Known liquids that can reversibly switch their polarity at atmospheric pressure are all prepared as mixtures of two liquid components; we now report a series of switchable-polarity solvents that consist, in their low-polarity form, of only a single liquid component, a secondary amine. These solvents operate in a polarity range that is significantly lower than those of previously reported switchable solvents. Application to the separation and purification of a polymer and recovery of a catalyst is described. [Abstract]

Herrero MA, Kremsner JM, Kappe CO
Nonthermal Microwave Effects Revisited: On the Importance of Internal Temperature Monitoring and Agitation in Microwave Chemistry.
J Org Chem. 2007 Dec 7;
The concept of nonthermal microwave effects has received considerable attention in recent years and is the subject of intense debate in the scientific community. Nonthermal microwave effects have been postulated to result from a direct stabilizing interaction of the electric field with specific (polar) molecules in the reaction medium that is not related to a macroscopic temperature effect. In order to probe the existence of nonthermal microwave effects, four synthetic transformations (Diels-Alder cycloaddition, alkylation of triphenylphosphine and 1,2,4-triazole, direct amide bond formation) were reevaluated under both microwave dielectric heating and conventional thermal heating. In all four cases, previous studies have claimed the existence of nonthermal microwave effects in these reactions. Experimentally, significant differences in conversion and/or product distribution comparing the conventionally and microwave-heated experiments performed at the same measured reaction temperature were found. The current reevaluation of these reactions was performed in a dedicated reactor setup that allowed accurate internal reaction temperature measurements using a multiple fiber-optic probe system. Using this technology, the importance of efficient stirring and internal temperature measurement in microwave-heated reactions was made evident. Inefficient agitation leads to temperature gradients within the reaction mixture due to field inhomogeneities in the microwave cavity. Using external infrared temperature sensors in some cases results in significant inaccuracies in the temperature measurement. Applying the fiber-optic probe temperature monitoring device, a critical reevaluation of all four reactions has provided no evidence for the existence of nonthermal microwave effects. Ensuring efficient agitation of the reaction mixture via magnetic stirring, no significant differences in terms of conversion and selectivity between experiments performed under microwave or oil bath conditions at the same internally measured reaction temperatures were experienced. The observed effects were purely thermal and not related to the microwave field. [Abstract]

Yusubov MS, Funk TV, Chi KW, Cha EH, Kim GH, Kirschning A, Zhdankin VV
Preparation and X-ray Structures of 3-[Bis(trifluoroacetoxy)iodo]benzoic Acid and 3-[Hydroxy(tosyloxy)iodo]benzoic Acid: New Recyclable Hypervalent Iodine Reagents.
J Org Chem. 2007 Dec 7;
Preparation, structural characterization, and reactivity of 3-[bis(trifluoroacetoxy)iodo]benzoic acid and 3-[hydroxy(tosyloxy)iodo]benzoic acid, new recyclable iodine(III) reagents derived from 3-iodosylbenzoic acid, are described. The reduced form of these reagents, 3-iodobenzoic acid, can be easily recovered from the reaction mixtures using ion-exchange resin or basic aqueous workup followed by acidification with HCl. [Abstract]

Usui K, Aso M, Fukuda M, Suemune H
Photochemical Generation of Oligodeoxynucleotide Containing a C4'-Oxidized Abasic Site and Its Efficient Amine Modification: Dependence on Structure and Microenvironment.
J Org Chem. 2007 Dec 7;
Bleomycin-induced oxidative DNA damage under limited oxygen conditions results in the formation of the C4'-oxidized abasic site (1). We synthesized the oligodeoxynucleotides (ODN) 5, which contains 4'-o-nitrobenzyloxythymidine (3), and 6, which contains 2-nitrobenzyloxy-4'-methoxy-2'-deoxy-d-ribofuranoside (4), as the caged precursors of 7, an ODN containing 1, to study its reactivity with amines. Photoirradiation of the single- and double-stranded 5 led to the formation of 7. Uncaging of the duplex was faster and the yield of 7 was higher with the double-stranded than with the single-stranded ODN. It was suggested that a low dielectric environment of the o-nitrobenzyloxy group in the minor groove of the duplex might accelerate the uncaging rate. Similarly, 6 and its duplex yielded 7 by photoirradiation. However, the yields of 7 were lower than those of 5, and duplex formation slowed the uncaging rate. Reaction of the obtained 7 with an amine resulted in the formation of the lactam 2b in good yield in both single- and double-stranded forms, showing that amine modification of biomolecules by an ODN containing 1 is possible under physiologic conditions. [Abstract]

Wang MC, Zhang QJ, Zhao WX, Wang XD, Ding X, Jing TT, Song MP
Evaluation of Enantiopure N-(Ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol for Catalytic Asymmetric Addition of Organozinc Reagents to Aldehydes.
J Org Chem. 2007 Dec 7;
A facile and practical approach to preparation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was developed from cheap and easily available l-(+)-methionine. Synthetic highlights include the three-step, one-pot construction of the chiral azetidine ring and the development of an improved one-step procedure for the synthesis of the key intermediate l-2-amino-4-bromobutanoic acid. Enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was evaluated for catalytic asymmetric addition of organozinc reagents to aldehydes. The asymmetric ethylation, methylation, arylation, and alkynylation of aldehydes achieved enantioselectivity of up to 98.4%, 94.1%, 99.0%, and 84.6% ee, respectively, in the presence of a catalytic amount of chiral N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol. Our results demonstrated further that the four-membered heterocycle-based backbone was a good potential chiral unit for the catalytic asymmetric induction reaction, and the hindrance of the bulky ferrocenyl group, compared to a phenyl group, played an important role in the enantioselectivities. A possible transition for the catalytic asymmetric addition has been proposed on the basis of the crystal structure of the chiral ligand 3b including two HOAc molecules and previous studies. [Abstract]

Ligthart GB, Guo D, Spek AL, Kooijman H, Zuilhof H, Sijbesma RP
Ureidobenzotriazine Multiple H-Bonding Arrays: The Importance of Geometrical Details on the Stability of H-Bonds.
J Org Chem. 2007 Dec 7;
A 3-ureidobenzo-1,2,4-triazine 1-N-oxide (1) was synthesized successfully. The derivative displays an acceptor-donor-acceptor-acceptor (ADAA) hydrogen-bonding motif in CDCl3 and DMSO-d6 solution as well as in the solid state. Although moderately strong association of 1 was observed with DAD motifs, nonspecific binding is observed with ureidopyridines featuring a complementary DADD array. Density functional calculations of conformations 1a and 1b together with two complexes revealed the clearly nonplanar geometry of the multiply hydrogen-bonded complex, in which some bonds are significantly longer (3.2 A) than is optimal for H-bonds. As a result, only very small free energies of association were calculated, in line with the experimentally observed absence of specific assembly of the components. [Abstract]

Ryoda A, Yajima N, Haga T, Kumamoto T, Nakanishi W, Kawahata M, Yamaguchi K, Ishikawa T
Optical Resolution of (+/-)-1,2-Bis(2-methylphenyl)ethylene-1,2-diamine as a Chiral Framework for 2-Iminoimidazolidine with 2-Methylphenyl Pendant and the Guanidine-Catalyzed Asymmetric Michael Reaction of tert-Butyl Diphenyliminoacetate and Ethyl Acrylate.
J Org Chem. 2007 Dec 7;
(+/-)-1,2-Bis(2-methylphenyl)ethylene-1,2-diamine, prepared from benzil and ammonium acetate, was optically resolved as a chiral framework for 2-(1-benzyl-2-hydroxyethyl)imino-1,3-dimethylimidazolidine with 2-methylphenyl pendants at the 4,5-positions. Catalysis ability of the 1,3-dimethyl-4,5-bis(2-methylphenyl)imidazolidine and the related 1,3-dibenzyl-4,5-diphenylimidazolidine was examined in the asymmetric Michael reaction of t-butyl diphenyliminoacetate and ethyl acrylate. [Abstract]

Greer EM, Aebisher D, Greer A, Bentley R
Computational Studies of the Tropone Natural Products, Thiotropocin, Tropodithietic Acid, and Troposulfenin. Significance of Thiocarbonyl-Enol Tautomerism.
J Org Chem. 2007 Dec 7;
Computations provide insight to the stability and isomeric possibilities of thiotropocin, tropodithietic acid, and troposulfenin. Thiotropocin and tropodithietic acid contain a flat 7-membered ring and delocalized pi-bonds similar to those of tropylium ion (C7H7+). Troposulfenin is far less stable; it contains a puckered tropone ring and localized bonds similar to 1,3,5-cycloheptatriene. A facile 1,5-hydrogen shift suggests that thiotropocin and tropodithietic acid exist as a pair of interconverting tautomers. Loss of an acidic proton from these three tautomers produces the same conjugate base structure. [Abstract]

Hanessian S, Vinci V, Fettis K, Maris T, Viet MT
Self-Assembly of Noncyclic Bis-d- and l-tripeptides into Higher Order Tubular Constructs: Design, Synthesis, and X-ray Crystal Superstructure.
J Org Chem. 2007 Dec 7;
Trans (1R,2R)-diaminocyclohexane was used as a semirigid vicinal diamine to anchor two N-protected tripeptides consisting of l-d-l amino acids as carboxy terminal amides. The bis-tripeptide consisting of l-Ser (OBn)-d-Ser (OBn)-l-Ser (O-p-bromobenzyl) Boc afforded X-ray quality crystals containing benzene and chloroform solvent molecules. Analysis of the solid-state structure revealed a highly H-bonded helical open-ended tubular superstructure. The tripeptide strands intertwine like a pair of self-embracing arms, held together by a gamma-turn and a 14-membered antiparallel H-bonded macroring spanning the first and third amino acid residues within each strand. Whereas the tripeptide from the R,R anchor gave beautiful crystals from benzene and chloroform, the analogous construct from the S,S-anchored diamine gave a gel. Related bis-tripeptides with different amino acids showed extensive intramolecular H-bonding based on NMR titration and dilution experiments. [Abstract]

Kim YK, Lee HN, Singh NJ, Choi HJ, Xue JY, Kim KS, Yoon J, Hyun MH
Anthracene Derivatives Bearing Thiourea and Glucopyranosyl Groups for the Highly Selective Chiral Recognition of Amino Acids: Opposite Chiral Selectivities from Similar Binding Units.
J Org Chem. 2007 Dec 6;
Two new anthracene thiourea derivatives, 1 and 2, were investigated as fluorescent chemosensors for the chiral recognition of the two enantiomers of alpha-amino carboxylates. Especially, host 2 displayed Kl/Kd values as high as 10.4 with t-Boc alanine. Furthermore, the d/l selectivity of hosts 1 and 2 is opposite, even though both hosts bear the same glucopyranosyl units. These intriguing opposite d/l binding affinities by 1 and 2 were obtained without/with H-pi interaction between anthrancene moiety and the methyl groups, which were explained by extensive high-level theoretical investigations taking into account the dispersion energy as well as the 2D-NMR chemical shifts. [Abstract]

Boeda F, Clavier H, Jordaan M, Meyer WH, Nolan SP
Phosphabicyclononane-Containing Ru Complexes: Efficient Pre-Catalysts for Olefin Metathesis Reactions.
J Org Chem. 2007 Dec 6;
The catalytic performances of three Phosphabicyclononane (Phoban)-containing ruthenium-based pre-catalysts have been evaluated for metathesis transformations. A wide screening of substrates in ring-closing metathesis reactions reveals the greater efficiency of pre-catalyst 4. Comparison of the catalytic activities of 4 with Grubbs' first-generation pre-catalyst illustrates the key role of the Phoban ligand. Additionally, a comparative study of three Phoban-containing pre-catalysts has been conducted for the self-metathesis of 1-octene at low catalyst loading (25-100 ppm). [Abstract]

Vale M, Pink M, Rajca S, Rajca A
Synthesis, Structure, and Conformation of Aza[1(n)()]metacyclophanes.
J Org Chem. 2007 Dec 6;
N-Benzyl substituted aza[1n]metacyclophanes (n = 4, 6, 8, and 10) were prepared in overall 40% isolated yields via Pd-catalyzed aminations. Analyses of the reaction mixtures showed that aza[14]metacyclophane and the related polymer were the primary products ( approximately 60% overall yield); aza[1n]metacyclophanes up to n = 14 and linear oligomers with up to 20 nitrogen atoms (with at least three types of end groups) were detected. Macrocyclic structures for n = 4, 6, and 10 were confirmed by X-ray crystallography. 1,3-Alternate (D2d) and 1,3,5-alternate (S6) conformations in solution on NMR time scale at low temperatures were found for macrocycles with n = 4 and n = 6, respectively; the barrier for ring inversion was considerably lower for the larger macrocycle. [Abstract]

Sasaki M, Tsubone K, Aoki K, Akiyama N, Shoji M, Oikawa M, Sakai R, Shimamoto K
Rapid and Efficient Synthesis of Dysiherbaine and Analogues to Explore Structure-Activity Relationships.
J Org Chem. 2007 Dec 6;
A rapid and efficient total synthesis of dysiherbaine (1), a potent and subtype-selective agonist for ionotropic glutamate receptors, has been accomplished. A key intermediate 15 was synthesized by two approaches. The first synthetic route utilized compound 9, an advanced intermediate in our previous total synthesis of neodysiherbaine A, as the starting point, and the cis-oriented amino alcohol functionality on the tetrahydropyran ring was installed by using an intramolecular SN2 cyclization of N-Boc-protected amino alcohol 20. An alternative and even more efficient synthetic approach to 15 featured stereoselective introduction of an amino group at C8 by iodoaminocyclization prior to constructing the bicyclic ether skeleton. The amino acid appendage was efficiently constructed by a catalytic asymmetric hydrogenation of enamide ester 36. The synthetic route developed here provided access to several dysiherbaine analogues, including 9-epi-dysiherbaine (38), 9-deoxydysiherbaine (39), 9-methoxydysiherbaine (40), and N-ethyldysiherbaine (41). The preliminary structure-activity relationship studies revealed that the presence and stereochemistry of the C9 hydroxy group in dysiherbaine is important for high-affinity and selective binding to glutamate subtype receptors. [Abstract]

Recent Articles in Journal of Mass Spectrometry

Shimma S, Nagao H, Giannakopulos AE, Hayakawa S, Awazu K, Toyoda M
High-energy collision-induced dissociation of phosphopeptides using a multi-turn tandem time-of-flight mass spectrometer 'MULTUM-TOF/TOF'
J Mass Spectrom. 2007 Dec 11; [Abstract]

Hoffner G, Hoppilliard Y, van der Rest G, Dansette P, Djian P, Ohanessian G
[N(epsilon)-(gamma-glutamyl) lysine] as a potential biomarker in neurological diseases : New detection method and fragmentation pathways.
J Mass Spectrom. 2007 Dec 6;
Protein aggregates are characteristic of a number of diseases of the central nervous system such as diseases of polyQ expansion. Covalent bonds formed by the action of transglutaminase are thought to participate in the stabilization of these aggregates. Transglutaminase catalyzes the formation of cross-links between the side chains of glutaminyl and lysyl residues of polypeptides. Identification of the isodipeptide N(epsilon)-(gamma-glutamyl) lysine (iEK) in terminal proteolytic digests of neuronal aggregates would demonstrate participation of transglutaminase in neurological diseases. In order to identify and quantify the iEK present in the brain of patients with neurological disease, a method combining liquid chromatography and multistep mass spectrometry was developed. Because isobaric peptides of iEK could be present in the digest of aggregated proteins, the choice of fragment diagnostic ions was crucial. These ions were identified by mass spectrometry on sodiated iEK, which was derivatized on the carboxylic functions and terminal amines in order to improve sensitivity. Deuterated molecules as well as (13)C(6)- and (15)N(2)-isotopomers were used to derive filiations in the multistep fragmentations. The main fragmentation patterns have been identified, so that two ions (m/z 396 [MH - 56-42 u](+) and 350 [MH - 56-88 u](+)) are shown to be adequate markers for quantitation experiments. In order to gain a better understanding of the fragmentation processes, detailed quantum chemical calculations have been performed at levels which are expected to provide good accuracy. A thorough study has been carried out with a reduced model in which only the 'active' part of the molecule is retained. This allowed obtaining full mechanistic details on the pathways leading to a number of observed fragments. In particular, it has been shown that losses of 87 and 88 u from A(+) = [MH - 56 u](+) are competitive. Computations on the entire derivatized isodipeptide have been used to validate the use of the smaller model in order to obtain reliable energetics and mechanisms. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Lamsabhi AM, M� O, Y��ez M, Guillemin JC, Haldys V, Tortajada J, Salpin JY
Ni(+) reactions with aminoacetonitrile, a potential prebiological precursor of glycine.
J Mass Spectrom. 2007 Dec 6;
The gas-phase reactions between Ni(+) ((2)D(5/2)) and aminoacetonitrile, a molecule of prebiological interest as possible precursor of glycine, have been investigated by means of mass spectrometry techniques. The mass-analyzed ion kinetic energy (MIKE) spectrum reveals that the adduct ions [NC--CH(2)--NH(2), Ni(+)] spontaneously decompose by loosing HCN, H(2), and H(2)CNH, the loss of hydrogen cyanide being clearly dominant. The structures and bonding characteristics of the aminoacetonitrile-Ni(+) complexes as well as the different stationary points of the corresponding potential energy surface (PES) have been theoretically studied by density functional theory (DFT) calculations carried out at B3LYP/6-311G(d,p) level. A cyclic intermediate, in which Ni(+) is bisligated to the cyano and the amino group, plays an important role in the unimolecular reactivity of these ions, because it is the precursor for the observed losses of HCN and H(2)CNH. In all mechanisms associated with the loss of H(2), the metal acts as hydrogen carrier favoring the formation of the H(2) molecule. The estimated bond dissociation energy of aminoacetonitrile-Ni(+) complexes (291 kJ mol(-1)) is larger than those measured for other nitrogen bases such as pyridine or pyrimidine and only slightly smaller than that of adenine. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Parker L, Engel-Hall A, Drew K, Steinhardt G, Helseth Jr DL, Jabon D, McMurry T, Angulo DS, Kron SJ
Investigating quantitation of phosphorylation using MALDI-TOF mass spectrometry.
J Mass Spectrom. 2007 Dec 6;
Despite advances in methods and instrumentation for analysis of phosphopeptides using mass spectrometry, it is still difficult to quantify the extent of phosphorylation of a substrate because of physiochemical differences between unphosphorylated and phosphorylated peptides. Here we report experiments to investigate those differences using MALDI-TOF mass spectrometry for a set of synthetic peptides by creating calibration curves of known input ratios of peptides/phosphopeptides and analyzing their resulting signal intensity ratios. These calibration curves reveal subtleties in sequence-dependent differences for relative desorption/ionization efficiencies that cannot be seen from single-point calibrations. We found that the behaviors were reproducible with a variability of 5-10% for observed phosphopeptide signal. Although these data allow us to begin addressing the issues related to modeling these properties and predicting relative signal strengths for other peptide sequences, it is clear that this behavior is highly complex and needs to be further explored. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Sun M, Dai W, Liu DQ
Fragmentation of aromatic sulfonamides in electrospray ionization mass spectrometry: elimination of SO(2) via rearrangement.
J Mass Spectrom. 2007 Dec 4;
Arylsulfonamides are attractive pharmacophores for drug candidates. Fragmentation behaviors of selected aromatic sulfonamides were investigated using electrospray ionization mass spectrometry in the positive ion mode. Some of the sulfonamides afforded unique loss of 64 (loss of SO(2)) ions upon collision-induced dissociation followed by intramolecular rearrangements in the gas phase. This SO(2) elimination-rearrangement pathway leading to the generation of [M + H - SO(2)](+) ions appeared to be susceptible to substitutions on the aromatic (Ar) ring that would affect the Ar--sulfur bond strength and the stability of the partially positive charge developed at the ipso position upon bond dissociation. Electron withdrawing groups such as chlorine attached to the aromatic ring at ortho position seem to promote the SO(2) extrusion. Although this fragmentation pathway in atmospheric pressure ionization MS is less predictable than in electron impact MS, it is a frequently encountered reaction. The absence of this fragmentation pathway in some of the arylsulfonamides indicates that other factors such as nucleophilicity of the nitrogen may also play a role in the process. With respect to the site of attachment of the migrating NR'R'', ipso-substitution on the aromatic ring is evident since this fragmentation mechanism is operative in the fully ortho-substituted arylsulfonamides. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Nomeir AA, Pramanik BN, Heimark L, Bennett F, Veals J, Bartner P, Hilbert M, Saksena A, McNamara P, Girijavallabhan V, Ganguly AK, Lovey R, Pike R, Wang H, Liu YT, Kumari P, Korfmacher W, Lin CC, Cacciapuoti A, Loebenberg D, Hare R, Miller G, Pickett C
Posaconazole (Noxafil, SCH 56592), a new azole antifungal drug, was a discovery based on the isolation and mass spectral characterization of a circulating metabolite of an earlier lead (SCH 51048).
J Mass Spectrom. 2007 Dec 4;
Posaconazole (SCH 56592) is a novel triazole antifungal drug that is marketed in Europe and the United States under the trade name 'Noxafil' for prophylaxis against invasive fungal infections. SCH 56592 was discovered as a possible active metabolite of SCH 51048, an earlier lead. Initial studies have shown that serum concentrations determined by a microbiological assay were higher than those determined by HPLC from animals dosed with SCH 51048. Subsequently, several animals species were dosed with (3)H-SCH 51048 and the serum was analyzed for total radioactivity, SCH 51048 concentration and antifungal activity. The antifungal activity was higher than that expected based on SCH 51048 serum concentrations, confirming the presence of active metabolite(s). Metabolite profiling of serum samples at selected time intervals pinpointed the peak that was suspected to be the active metabolite. Consequently, (3)H-SCH 51048 was administered to a large group of mice, the serum was harvested and the metabolite was isolated by extraction and semipreparative HPLC. LC-MS/MS analysis suggested that the active metabolite is a secondary alcohol with the hydroxyl group in the aliphatic side chain of SCH 51048. All corresponding monohydroxylated diastereomeric mixtures were synthesized and characterized. The HPLC retention time and LC-MS/MS spectra of the diastereomeric secondary alcohols of SCH 51048 were similar to those of the isolated active metabolite. Finally, all corresponding individual monohydroxylated diasteriomers were synthesized and evaluated for in vitro and in vivo antifungal potencies, as well as pharmacokinetics. SCH 56592 emerged as the candidate with the best overall profile. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Giorgi G, Palumbo Piccionello A, Pace A, Buscemi S
Hydration/elimination reactions of trapped protonated fluoroalkyl triazines.
J Mass Spectrom. 2007 Nov 26; [Abstract]

Van Berkel GJ, Kertesz V, Koeplinger KA, Vavrek M, Kong AN
Liquid microjunction surface sampling probe electrospray mass spectrometry for detection of drugs and metabolites in thin tissue sections.
J Mass Spectrom. 2007 Nov 26;
A self-aspirating, liquid microjunction surface sampling probe/electrospray emitter mass spectrometry system was demonstrated for use in the direct analysis of spotted and dosed drugs and their metabolites in thin tissue sections. Proof-of-principle sampling and analysis directly from tissue without the need for sample preparation was demonstrated first by raster scanning a region on a section of rat liver onto which reserpine was spotted. The mass spectral signal from selected reaction monitoring was used to develop a chemical image of the spotted drug on the tissue. The probe was also used to selectively spot sample areas of sagittal whole-body tissue from a mouse that had been dosed orally (90 mg/kg) with R,S-sulforaphane 3 h prior to sacrifice. Sulforaphane and its glutathione and N-acetyl cysteine conjugates were monitored with selected reaction monitoring and detected in the stomach and various other tissues from the dosed mouse. No signal for these species was observed in the tissue from a control mouse. The same dosed-tissue section was used to illustrate the possibility of obtaining a lane scan across the whole-body section. In total, these results illustrate the potential for rapid screening of the distribution of drugs and metabolites in thin tissue sections with the liquid micro-junction surface sampling probe/electrospray mass spectrometry approach. Published in 2007 by John Wiley & Sons, Ltd. [Abstract]

Pozo OJ, Van Thuyne W, Deventer K, Van Eenoo P, Delbeke FT
Elucidation of urinary metabolites of fluoxymesterone by liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry.
J Mass Spectrom. 2007 Nov 26;
The suitability of liquid chromatography tandem mass spectrometry (LC-MS/MS) and gas chromatography mass spectrometry (GC-MS) for the elucidation of fluoxymesterone metabolism has been evaluated. Electrospray ionization (ESI) and collision induced dissociation (CID) fragmentation in LC-MS/MS and electron impact spectra (EI) in GC-MS have been studied for fluoxymesterone and two commercially available metabolites. MS(n) experiments and accurate mass measurements performed by an ion-trap analyser and a QTOF instrument respectively have been used for the elucidation of the fragmentation pathway. The neutral loss scan of 20 Da (loss of HF) in LC-MS/MS has been applied for the selective detection of fluoxymesterone metabolites. In a positive fluoxymesterone doping control sample, 9 different analytes have been detected including the parent compound. Seven of these metabolites were also confirmed by GC-MS including 5 previously unreported metabolites. On the basis of the ionization, the CID fragmentation, the accurate mass of the product ions and the EI spectra of these analytes, a tentative elucidation as well as a proposal for the metabolic pathway of fluoxymesterone has been suggested. The presence of these compounds has also been confirmed by the analysis of five other positive fluoxymesterone urine samples. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Zaitsu K, Katagi M, Kamata H, Kamata T, Shima N, Miki A, Iwamura T, Tsuchihashi H
Discrimination and identification of the six aromatic positional isomers of trimethoxyamphetamine (TMA) by gas chromatography-mass spectrometry (GC-MS).
J Mass Spectrom. 2007 Nov 26;
A reliable and accurate GC-MS method was developed that allows both mass spectrometric and chromatographic discrimination of the six aromatic positional isomers of trimethoxyamphetamine (TMA). Regardless of the trifluoroacetyl (TFA) derivatization, chromatographic separation of all the investigated isomers was achieved by using DB-5ms capillary columns (30 m x 0.32 mm i.d.), with run times less than 15 min. However, the mass spectra of the nonderivatized TMAs, except 2,4,6-trimethoxyamphetmine (TMA-6), showed insufficient difference for unambiguous discrimination. On the other hand, the mass spectra of the TFA derivatives of the six isomers exhibited fragments with significant intensity differences, which allowed the unequivocal identification of all the aromatic positional isomers investigated in the present study. This GC-MS technique in combination with TFA derivatization, therefore, is a powerful method to discriminate these isomers, especially useful to distinguish the currently controlled 3,4,5-trimethoxyamphetmine (TMA-1) and 2,4,5-trimethoxyamphetmine (TMA-2) from other uncontrolled TMAs. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Wang P, Polce MJ, Ohanessian G, Wesdemiotis C
The sodium ion affinities of cytosine and its methylated derivatives.
J Mass Spectrom. 2007 Nov 12;
The sodium ion affinities of cytosine (Cyt), 5-methylcytosine (5MeCyt) and 1-methylcytosine (1MeCyt) have been determined by experimental and quantum chemical methods. Na(+)-bound heterodimers were produced carrying one cytosine or methylated cytosine ligand (designated as C) and one peptide or amino acid reference base (designated as Pep); the Pep molecules included the peptides GlyLeu, GlyPhe, SerGly, and PheGly, and the amino acid His. The dissociation kinetics of these C--Na(+)--Pep ions were determined by collisionally activated dissociation (CAD) and converted to relative and absolute Na(+) affinities via kinetic method approaches. Relative Na(+) affinities increase in the order (kJ/mol): GlyLeu (0) < Cyt (3) < GlyPhe (4) < SerGly (6) < 5MeCyt (8) < PheGly (11) < 1MeCyt (13) < His (17). Anchoring the relative values of the nucleobases to the absolute affinities of the reference bases leads to absolute Na(+) affinities of 214 +/- 8, 219 +/- 8, and 224 +/- 8 kJ/mol for Cyt, 5MeCyt, and 1MeCyt, respectively. Ab initio calculations were used to confirm these results. The computed affinities of Cyt (213 kJ/mol) and 1MeCyt (217 kJ/mol) are in very good agreement with the experiments. These values unambiguously correspond to Na(+) complexes with the keto form of cytosine and its methyl derivatives. Ab initio calculations on tautomerization mechanisms in the gas versus condensed phase are used to discuss why the sodiated keto isomers were formed in the present electrospray ionization (ESI) experiments, but the enol isomers in previous fast atom bombardment (FAB) experiments. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Huang C, Hu B, He M, Duan J
Organic and inorganic selenium speciation in environmental and biological samples by nanometer-sized materials packed dual-column separation/preconcentration on-line coupled with ICP-MS.
J Mass Spectrom. 2007 Nov 12;
A novel, fast, and cheap nonchromatographic method for direct speciation of dissolved inorganic and organic selenium species in environmental and biological samples was developed by flow injection (FI) dual-column preconcentration/separation on-line coupled with ICP-MS determination. In the developed technique, the first column packed with nanometer-sized Al(2)O(3) could selectively adsorb the inorganic selenium [Se(IV), Se(VI)], and the retained inorganic selenium could be eluted by 0.2 mol l(-1) NaOH, while the organic Se [selenocystine (SeCys(2)) and selenomethionine (Se-Met)] was not retained. On the other hand, the second column packed with mesoporous TiO(2) chemically modified by dimercaptosuccinic acid (DMSA) could selectively adsorb Se(IV) and SeCys(2) and barely adsorb Se(VI) and Se-Met. When the sample solution was passed through the column 1, separation of inorganic selenium and organic selenium could be achieved first. Then, the effluent from column 1 was successively introduced into the column 2 and the speciation of organic selenium could be attained due to the different adsorption behaviors of Se-Met and SeCys(2) on DMSA modified TiO(2). After that, the eluent from column 1 contained Se(IV), and Se(VI) was adjusted to desired pH and injected into column 2, and the speciation of Se(IV) and Se(VI) could also be realized thanks to their different retention on column 2. The parameters affecting the separation were investigated systematically and the optimal separation conditions were established. The detection limits obtained for Se(IV), Se(VI), Se-Met and SeCys(2) were 45-210 ng l(-1) with precisions of 3.6-9.7%. The proposed method has been successfully applied for the speciation of dissolved inorganic and organic selenium in environmental and biological samples. In order to validate the methodology, the developed method was also applied to the speciation of selenium in certified reference material of SELM-1 yeast, and the determined values were in good agreement with the certified values. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Pak A, Lesage D, Gimbert Y, V�key K, Tabet JC
Internal energy distribution of peptides in electrospray ionization : ESI and collision-induced dissociation spectra calculation.
J Mass Spectrom. 2007 Nov 2;
The internal energy of ions and the timescale play fundamental roles in mass spectrometry. The main objective of this study is to estimate and compare the internal energy distributions of different ions (different nature, degree of freedom 'DOF' and fragmentations) produced in an electrospray source (ESI) of a triple-quadrupole instrument (Quattro I Micromass). These measurements were performed using both the Survival Yield method (as proposed by De Pauw) and the MassKinetics software (kinetic model introduced by V�key). The internal energy calibration is the preliminary step for ESI and collision-induced dissociation (CID) spectra calculation. meta-Methyl-benzylpyridinium ion and four protonated peptides (YGGFL, LDIFSDF, LDIFSDFR and RLDIFSDF) were produced using an electrospray source. These ions were used as thermometer probe compounds. Cone voltages (V(c)) were linearly correlated with the mean internal energy values (<E(int) >) carried by desolvated ions. These mean internal energy values seem to be slightly dependent on the size of the studied ion. ESI mass spectra and CID spectra were then simulated using the MassKinetics software to propose an empirical equation for the mean internal energy (<E(int) >) versus cone voltage (V(c)) for different source temperatures (T): < E(int) > = [405 x 10(-6) - 480 x 10(-9) (DOF)] V(c)T + E(therm)(T). In this equation, the E(therm)(T) parameter is the mean internal energy due to the source temperature at 0 V(c). Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Marjasvaara A, J�nis J, Vainiotalo P
Oxidation of a laccase mediator ABTS as studied by ESI-FTICR mass spectrometry.
J Mass Spectrom. 2007 Nov 2;
The oxidation reaction of a laccase mediator ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) was studied by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICRMS). Oxidation products of ABTS were measured after reaction times that varied from a few minutes up to several days and both positive and negative ionization modes were employed. Exact mass measurements and collision-induced dissociation (CID) experiments were used to characterize the structures of the ions formed. After reacting with Trametes versicolor laccase (TvL), the radical cation form of ABTS was the main product observed by the positive ionization mode. Negative ionization mode experiments revealed that a degradation product from ABTS was formed. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Silipo A, De Castro C, Lanzetta R, Molinaro A, Parrilli M, Vago G, Sturiale L, Messina A, Garozzo D
Structural characterizations of lipids A by MS/MS of doubly charged ions on a hybrid linear ion trap/orbitrap mass spectrometer.
J Mass Spectrom. 2007 Nov 2;
Here, a new 'one pot' and fast approach is described, based on electrospray ionization (ESI) of negative ions by using a hybrid linear ion trap/orbitrap mass spectrometer (LTQ/orbitrap) for MS and MS/MS analysis. By this method the distribution of the primary and secondary acyl residues of the intact lipid A is inferred by analysis of the ESI spectra measured in positive and negative mode. The analysis of these data allows an unequivocal assignment of the fatty acid distribution. This methodology was successfully tested on two different lipid A with known structures, deriving from the Agrobacterium tumefaciens and Escherichia coli lipopolysaccharides (LPS). Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Johnson DW
A flow injection electrospray ionization tandem mass spectrometric method for the simultaneous measurement of trimethylamine and trimethylamine N-oxide in urine.
J Mass Spectrom. 2007 Nov 2;
Key metabolites for the diagnosis of the genetic disorder trimethylaminuria are trimethylamine (TMA) and trimethylamine N-oxide (TMAO). A rapid, automatable flow injection ESI-MS/MS method for their measurement in urine has been developed. The TMA was derivatized with ethyl bromoacetate to form ethyl betaine bromide. The 2 min ESI-MS/MS analysis employed four multiple reaction monitoring (MRM) ion pairs for derivatized TMA (146.1, 118.1), derivatized (2)H(9)-TMA (155.1, 127.1), TMAO (76.1, 58.1) and (2)H(9)-TMAO (85.1, 66.1). In control urine samples (n = 27) referred for suspected metabolic problems TMA was 0.11-1.19 mmol/mol creatinine, TMAO was 13.5-181 mmol/mol creatinine and the TMA/TMAO ratio was 0.0025-0.055. In five patients with diagnosed trimethylaminuria, TMA was 5.3-230 mmol/mol creatinine, TMAO was 0.36-607 mmol/mol creatinine and the TMA/TMAO ratio was 0.20-134. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Gabant G, Augier J, Armengaud J
Assessment of solvent residues accessibility using three Sulfo-NHS-biotin reagents in parallel: application to footprint changes of a methyltransferase upon binding its substrate.
J Mass Spectrom. 2007 Oct 29;
NHS-biotin modification as a specific lysine probe coupled to mass spectrometry detection is increasingly used over the past years for assessing amino acid accessibility of proteins or complexes as an alternative when well-established methods are challenged. We present a strategy based on usage in parallel of three commercially available reagents (Sulfo-NHS-biotin, Sulfo-NHS-LC-biotin, and Sulfo-NHS-LC-LC-biotin) to efficiently assess the solvent accessibility of amino acids using MALDI-TOF mass spectrometry. The same qualitative pattern of reactivity was observed for these three reagents on the THUMPalpha protein at four reagent/polypeptide molar ratios (2 : 1, 6 : 1, 13 : 1, and 26 : 1). Peptide assignment of the detected ions gains in accuracy because of the triple redundancy due to specific increments of monoisotopic mass. These reagents are a good alternative to isotope labeling when using only a single MALDI-TOF mass spectrometer. We observed that hydroxyl groups of serine and tyrosine residues were also modified by these Sulfo-NHS-biotin reagents. The low amount of protein required and the method's simplicity make this procedure accessible and affordable in order to obtain topological information on proteins difficult to purify. This method was used to identify two lysine residues of the TrmG10 methyltransferase from Pyrococcus abyssi that were differentially reactive, modified in the protein but not in the tRNA-protein complex. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Sauer C, Peters FT, Staack RF, Fritschi G, Maurer HH
New designer drugs N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA) and N-(1-phenylcyclohexyl)-2-methoxyethanamine (PCMEA): Studies on their metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques.
J Mass Spectrom. 2007 Oct 29;
Studies are described on the metabolism and the toxicological detection of the phencyclidine-derived designer drugs N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA) and N-(1-phenylcyclohexyl)-2-methoxyethanamine (PCMEA) in rat urine using gas chromatographic/mass spectrometric (GC/MS) techniques. The identified metabolites indicated that PCEEA and PCMEA were transformed to the same metabolites by N-dealkylation and O-dealkylation partially followed by oxidation of the resulting alcohol to the respective carboxylic acid and hydroxylation of the cyclohexyl ring at different positions and combinations of those. Finally, aromatic hydroxylation of the O-dealkylated metabolites was partially followed by hydroxylation of the cyclohexyl ring at different positions. All metabolites were partially excreted in conjugated form. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of an intake of a common drug users' dose both of PCEEA and PCMEA in rat urine. Assuming similar metabolism in humans, the STA should be suitable for proof of an intake of PCEEA and PCMEA in human urine, although their differentiation is not possible due to common metabolites. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Madhusudanan KP, Srivastava M
Identification of hexose diastereomers by means of tandem mass spectrometry of oxocarbenium ions followed by neural networks analysis.
J Mass Spectrom. 2007 Oct 29;
The ion abundances in the tandem mass spectra of oxocarbenium ions generated from aldohexoses and ketohexoses under electrospray ionization conditions depend on their stereochemistry. The ratios of the abundances of two of the major ions m/z 85 and 91 are different in the aldohexoses and the ketohexoses. Principal component analysis (PCA) allowed visual differentiation of the hexose isomers. However, identification of an individual hexose was difficult. The data were subjected to neural network analysis (NNA) using a multilayer perceptron (MLP) model. The model was first trained using the data from the 11 hexoses and then used to identify the hexoses using fresh data acquired later. There was 100% identification of the various hexoses. The hexose units in methyl glucoside, mannoside and galactoside could also be identified accurately. The method can therefore be used for the characterization of hexose units from monosaccharides and glycosides. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Ruan Q, Peterman S, Szewc MA, Ma L, Cui D, Humphreys WG, Zhu M
An integrated method for metabolite detection and identification using a linear ion trap/Orbitrap mass spectrometer and multiple data processing techniques: application to indinavir metabolite detection.
J Mass Spectrom. 2007 Oct 29;
A new strategy using a hybrid linear ion trap/Orbitrap mass spectrometer and multiple post-acquisition data mining techniques was evaluated and applied to the detection and characterization of in vitro metabolites of indinavir. Accurate-mass, full-scan MS and MS/MS data sets were acquired with a generic data-dependent method and processed with extracted-ion chromatography (EIC), mass-defect filter (MDF), product-ion filter (PIF), and neutral-loss filter (NLF) techniques. The high-resolution EIC process was shown to be highly effective in the detection of common metabolites with predicted molecular weights. The MDF process, which searched for metabolites based on the similarity of mass defects of metabolites to those of indinavir and its core substructures, was able to find uncommon metabolites not detected by the EIC processing. The high-resolution PIF and NLF processes selectively detected metabolites that underwent fragmentation pathways similar to those of indinavir or its known metabolites. As a result, a total of 15 metabolites including two new indinavir metabolites were detected and characterized in a rat liver S9 incubation sample. Overall, these data mining techniques, which employed distinct metabolite search mechanisms, were complementary and effective in detecting both common and uncommon metabolites. In summary, the results demonstrated that this analytical strategy enables the high-throughput acquisition of accurate-mass LC/MS data sets, comprehensive search of a variety of metabolites through the post-acquisition processes, and effective structural characterization based on elemental compositions of metabolite molecules and their product ions. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Hol?apek M, L�sa M, Voln� K, Almonasy N, P?ikryl J
Occurrence of radical molecular ions in atmospheric pressure chemical ionization mass spectra of heterocyclic compounds.
J Mass Spectrom. 2007 Oct 29; [Abstract]

Wang Z, Guo X, Liu Z, Cui M, Song F, Liu S
Studies on alkaloids binding to GC-rich human survivin promoter DNA using positive and negative ion electrospray ionization mass spectrometry.
J Mass Spectrom. 2007 Oct 29;
Electrospray ionization mass spectrometry (ESI-MS) was used to investigate the binding of 13 alkaloids to two GC-rich DNA duplexes which are critical sequences in human survivin promoter. Negative ion ESI-MS was first applied to screen the binding of the alkaloids to the duplexes. Six alkaloids (including berberine, jatrorrhizine, palmatine, reserpine, berbamine, and tetrandrine) show complexation with the target DNA sequences. Relative binding affinities were estimated from the negative ion ESI data, and the alkaloids show a binding preference to the duplex with higher GC content. Positive ion ESI mass spectra of the complexes were also recorded and compared with those obtained in negative ion mode. Only the 1 : 1 complex with berbamine was observed with lower abundance in the positive ion mass spectrum while complexes with the other alkaloids were absolutely absent. Collision-induced dissociation (CID) experiments indicate that the complexes with the protoberberine alkaloids (berberine, jatrorrhizine, and palmatine) dissociate via base loss and covalent cleavage. In contrast, product ion spectra of the complexes with the alkaloids reserpine, berbamine, and tetrandrine show the predominant loss of a neutral alkaloid molecule, accompanied by base loss and covalent cleavage to a lesser extent. A comparison of the gas-phase behaviors of complexes with the alkaloids to those with the traditional DNA binders has suggested an intercalative binding mode of these alkaloids to the target DNA duplexes. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Zhang X, Rogowska-Wrzesinska A, Roepstorff P
On-target sample preparation of 4-sulfophenyl isothiocyanate-derivatized peptides using AnchorChip Targets.
J Mass Spectrom. 2007 Oct 29;
De novo sequencing of tryptic peptides by post source decay (PSD) or collision induced dissociation (CID) analysis using MALDI TOF-TOF instruments is due to the easy interpretation facilitated by the introduction of N-terminal sulfonated derivatives. Recently, a stable and cheap reagent, 4-sulfophenyl isothiocyanate (SPITC), has been successfully used for N-terminal derivatization. Previously described methods have always used desalting and concentration by reverse-phase chromatography prior to mass spectrometric analysis. Here we present an on-target sample preparation method based on AnchorChip target technology. The method was optimized for reduction of by-products and sensitivity with SPITC-derivatized tryptic BSA peptides, and successfully applied to protein identification from silver-stained two-dimensional electrophoretic gels of fish liver extracts. The method is simple and sensitive and allowed protein identification based on de novo sequencing and BLAST search from species with limited sequence information. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

G�mez-Gonz�lez Y, Surratt JD, Cuyckens F, Szmigielski R, Vermeylen R, Jaoui M, Lewandowski M, Offenberg JH, Kleindienst TE, Edney EO, Blockhuys F, Van Alsenoy C, Maenhaut W, Claeys M
Characterization of organosulfates from the photooxidation of isoprene and unsaturated fatty acids in ambient aerosol using liquid chromatography/(-) electrospray ionization mass spectrometry.
J Mass Spectrom. 2007 Oct 29;
In the present study, we have characterized in detail the MS(2) and MS(3) fragmentation behaviors, using electrospray ionization (ESI) in the negative ion mode, of previously identified sulfated isoprene secondary organic aerosol compounds, including 2-methyltetrols, 2-methylglyceric acid, 2-methyltetrol mononitrate derivatives, glyoxal and methylglyoxal. A major fragmentation pathway for the deprotonated molecules of the sulfate esters of 2-methyltetrols and 2-methylglyceric acid and of the sulfate derivatives of glyoxal and methylglyoxal is the formation of the bisulfate [HSO(4)](-) anion, while the deprotonated sulfate esters of 2-methyltetrol mononitrate derivatives preferentially fragment through loss of nitric acid. Rational interpretation of MS(2), MS(3) and accurate mass data led to the structural characterization of unknown polar compounds in K-puszta fine aerosol as organosulfate derivatives of photooxidation products of unsaturated fatty acids, i.e. 2-hydroxy-1,4-butanedialdehyde, 4,5- and 2,3-dihydroxypentanoic acids, and 2-hydroxyglutaric acid, and of alpha-pinene, i.e. 3-hydroxyglutaric acid. The deprotonated molecules of the sulfated hydroxyacids, 2-methylglyceric acid, 4,5- and 2,3-dihydroxypentanoic acid, and 2- and 3-hydroxyglutaric acids, showed in addition to the [HSO(4)](-) ion (m/z 97) neutral losses of water, CO(2) and/or SO(3), features that are characteristic of humic-like substances. The polar organosulfates characterized in the present work are of climatic relevance because they may contribute to the hydrophilic properties of fine ambient aerosol. In addition, these compounds probably serve as ambient tracer compounds for the occurrence of secondary organic aerosol formation under acidic conditions. Copyright (c) 2007 John Wiley & Sons, Ltd. [Abstract]

Current literature in mass spectrometry.
J Mass Spectrom. 2007 Nov;42(11):1522-9.
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Reviews; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (4 Weeks journals - Search completed at 15th. Aug. 2007). [Abstract]

Oliveira E, Amara I, Bellido D, Odena MA, Dom�nguez E, Pag�s M, Goday A
LC-MSMS identification of Arabidopsis thaliana heat-stable seed proteins: enriching for LEA-type proteins by acid treatment.
J Mass Spectrom. 2007 Nov;42(11):1485-95.
Protein identification in systems containing very highly abundant proteins is not always efficient and usually requires previous enrichment or fractionation steps in order to uncover minor proteins. In plant seeds, identification of late embryogenesis abundant (LEA) proteins is often masked by the presence of the large family of storage proteins. LEA-proteins are predicted to play a role in plant stress tolerance. They are highly hydrophilic proteins, generally heat-stable, and correlate with dehydration in seeds or vegetative tissues. In the present work, we analyze the protein composition of heat-stable Arabidopsis thaliana seed extracts after treatment with trichloroacetic acid (TCA). The composition of the proteins that precipitate and those that remain in solution in 3% TCA was analyzed by two different approaches: 1D SDS-PAGE coupled to LC-ESI-MSMS analysis and a gel-free protocol associated with LC-MALDI-MSMS. Our results indicate that treating total heat-soluble extracts with 3% TCA is an effective procedure to remove storage proteins by selective precipitation and this fractionation step provides a soluble fraction highly enriched in Lea-type proteins. The analysis and determination of protein identities in this acid-soluble fraction by MS technology is a suitable system for large-scale identification of Lea-proteins present in seeds. [Abstract]

Gharbi S, Garz�n B, Gayarre J, Timms J, P�rez-Sala D
Study of protein targets for covalent modification by the antitumoral and anti-inflammatory prostaglandin PGA1: focus on vimentin.
J Mass Spectrom. 2007 Nov;42(11):1474-84.
Prostaglandins with cyclopentenone structure (cyPG) display potent antiproliferative actions that have elicited their study as potential anticancer agents. Several natural and synthetic analogs of the cyPG prostaglandin A(1) (PGA(1)) have proven antitumoral efficacy in cancer cell lines and animal models. In addition, PGA(1) has been used as an inhibitor of transcription factor NF-kappaB-mediated processes, including inflammatory gene expression and viral replication. An important determinant for these effects is the ability of cyPG to form Michael adducts with free thiol groups. The chemical nature of this interaction implies that PGA(1) could covalently modify cysteine residues in a large number of cellular proteins potentially involved in its beneficial effects. However, only a few targets of PGA(1) have been identified. In previous work, we have observed that a biotinylated analog of PGA(1) that retains the cyclopentenone moiety (PGA(1)-B) binds to multiple targets in fibroblasts. Here, we have addressed the identification of these targets through a proteomic approach. Cell fractionation followed by avidin affinity chromatography yielded a fraction enriched in proteins modified by PGA(1)-B. Analysis of this fraction by SDS-PAGE and LC-MS/MS allowed the identification of the chaperone Hsp90, elongation and initiation factors for protein synthesis and cytoskeletal proteins including actin, tubulin and vimentin. Furthermore, we have characterized the modification of vimentin both in vitro and in intact cells. Our observations indicate that cysteine 328 is the main site for PGA(1) addition. These results may contribute to a better understanding of the mechanism of action of PGA(1) and the potential of cyPG-based therapeutic strategies. [Abstract]

Mor�n M, Monteoliva L, Insenser M, Gil C, Dom�nguez A
Proteomic analysis reveals metabolic changes during yeast to hypha transition in Yarrowia lipolytica.
J Mass Spectrom. 2007 Nov;42(11):1453-62.
Fungal dimorphism is important for survival in different environments and has been related to virulence. The ascomycete Yarrowia lipolytica can grow as yeast, pseudomycelial or mycelial forms. We have used a Y. lipolytica parental strain and a Deltahoy1 mutant, which is unable to form hypha, to set up a model for dimorphism and to characterize in more depth the yeast to hypha transition by proteomic techniques. A two-dimensional gel electrophoresis (2-DE) based differential expression analysis of Y. lipolytica yeast and hyphal cells was performed, and 45 differentially expressed proteins were detected; nine with decreased expression in hyphal cells were identified. They corresponded to the S. cerevisiae homologues of Imd4p, Pdx3p, Cdc19, Sse1p, Sol3p, Sod2p, Xpt1p, Mdh1p and to the unknown protein YALIOB00924g. Remarkably, most of these proteins are involved in metabolic pathways, with four showing oxidoreductase activity. Furthermore, taking into account that this is the first report of 2-DE analysis of Y. lipolytica protein extracts, 35 more proteins from the 2D map of soluble yeast proteins, which were involved in metabolism, cell rescue, energy and protein synthesis, were identified. [Abstract]

De Jesus JB, Cuervo P, Junqueira M, Britto C, Silva-Filho FC, Sab�ia-Vahia L, Gonz�lez LJ, Barbosa Domont G
Application of two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for proteomic analysis of the sexually transmitted parasite Trichomonas vaginalis.
J Mass Spectrom. 2007 Nov;42(11):1463-73.
Trichomonas vaginalis is a sexually transmitted protozoan parasite that infects the human urogenital tract causing trichomoniasis, a worldwide disease. In this work, a fresh clinical isolate of T. vaginalis was used for study of the protein expression in this species. Two-dimensional gel electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry (MS) were employed to create a reference map of soluble proteins in the pH range 4-7. A set of 116 proteins belonging to functional classes expressed in high and low abundance was identified by peptide mass fingerprinting and tandem MS. These identifications corresponded to 67 different proteins, suggesting that post-translational modifications are common phenomena in T. vaginalis. Identified proteins were classified into 16 groups according to biological processes. Among detected proteins we identified the major enzymes involved in both cytosolic and hydrogenosomal metabolic pathways, as well as putative protein targets for new drug design. In addition, this analysis allows validation of previous gene predictions confirming the expression of 15 hypothetical proteins. Finally, the findings here reported represent the first reference proteome map of T. vaginalis and the first steps towards the description of a comprehensive proteome map of this parasite. [Abstract]

Henning S, Peter-Katalini? J, Pohlentz G
Structure elucidation of glycoproteins by direct nanoESI MS and MS/MS analysis of proteolytic glycopeptides.
J Mass Spectrom. 2007 Nov;42(11):1415-21.
Bovine ribonuclease B (RNAse B) and asialofetuin (FETUA) were subjected to in-capillary tryptic digest (Pohlentz et al. Proteomics. 2005, 5, 1758-1763) and the obtained glycopeptides were analyzed, respectively, by nanoelectrospray ionization mass spectrometry and collision-induced dissociation (CID) during the ongoing digest. For RNAse, B glycans of the high-mannose type (Man(4) to Man(9)) attached to either a tetra- or a hexapeptide containing the sole N-glycosylation site of the protein were detected. Glycopeptides derived from all three N-glycosylation sites of FETUA were observed, and the corresponding CID spectra proved the respective glycans to be oligosaccharides of the triantennary complex type. Moreover, an O-glycopeptide carrying Gal-GalNAc at T(280) could be unambiguously identified. An in-solution tryptic/chymotryptic digest of human transferrin (TRFE) was analyzed directly for glycopeptides subsequent to the addition of methanol and formic acid. Disialylated diantennary glycans were observed in glycopeptides of both N-glycosylation sites of TRFE. These results demonstrate the feasibility of direct structure determination of glycopeptides in proteolytic mixtures without any further refurbishment. [Abstract]