- Switching Lysophosphatidylserine G Protein-Coupled Receptor Agonists to Antagonists by Acylation of the Hydrophilic Serine Amine
-
Three human G protein-coupled receptors (GPCRs)—GPR34/LPS1, P2Y10/LPS2, and GPR174/LPS3—are activated specifically by lysophosphatidylserine (LysoPS), an endogenous hydrolysis product of a cell membrane component, phosphatidylserine (PS). LysoPS consists of-serine, glycerol, and fatty acid moieties connected by phosphodiester and ester linkages. We previously generated potent and selective GPCR agonists by modification of the three modules and the ester linkage. Here, we show that a novel modification of the hydrophilic serine moiety, that is, N-acylations of the serine amine, converted a GPR174 agonist to potent GPR174 antagonists. Structural exploration of the amide functionality provided access to a range of activities from agonist to partial agonist to antagonist. The present study would provide a new strategy for the development of lysophospholipid receptor antagonists.
- Sayama, Misa,Uwamizu, Akiharu,Ikubo, Masaya,Chen, Luying,Yan, Ge,Otani, Yuko,Inoue, Asuka,Aoki, Junken,Ohwada, Tomohiko
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p. 10059 - 10101
(2021/07/28)
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- Synthesis and antimicrobial activity of phosphonopeptide derivatives incorporating single and dual inhibitors
-
In diagnostic microbiology, culture media are widely used for detection of pathogenic bacteria. Such media employ various ingredients to optimize detection of specific pathogens such as chromogenic enzyme substrates and selective inhibitors to reduce the presence of commensal bacteria. Despite this, it is rarely possible to inhibit the growth of all commensal bacteria, and thus pathogens can be overgrown and remain undetected. One approach to attempt to remedy this is the use of “suicide substrates” that can target specific bacterial enzymes and selectively inhibit unwanted bacterial species. With the purpose of identifying novel selective inhibitors, six novel phosphonopeptide derivatives based on D/L-fosfalin and β-chloro-L-alanine were synthesized and tested on 19 different strains of clinically relevant bacteria. Several compounds show potential as useful selective agents that could be exploited in the recovery of several bacterial pathogens including Salmonella, Pseudomonas aeruginosa, and Listeria.
- Anderson, Rosaleen J.,Gray, Mark,Marrs, Emma C. L.,Ng, Keng Tiong,Orenga, Sylvain,Perry, John D.
-
supporting information
(2020/04/10)
-
- Phosphonopeptides revisited, in an era of increasing antimicrobial resistance
-
Given the increase in resistance to antibacterial agents, there is an urgent need for the development of new agents with novel modes of action. As an interim solution, it is also prudent to reinvestigate old or abandoned antibacterial compounds to assess
- Anderson, Rosaleen J.,Bedernjak, Alexandre F.,Cummings, Stephen P.,Day, Kathryn M.,Gray, Mark,Jones, Amanda L.,Marrs, Emma C. L.,Perry, John D.,Varadi, Linda
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supporting information
(2020/03/26)
-
- PROTEIN KINASE MKK4 INHIBITORS FOR PROMOTING LIVER REGENERATION OR REDUCING OR PREVENTING HEPATOCYTE DEATH
-
The invention relates to pyrazolo-pyridine compounds which inhibit mitogen-activated protein kinase kinase 4 (MKK4) and in particular, selectively inhibit MKK4 over protein kinases JNK1 and MKK7. The compounds are useful for promoting liver regeneration or reducing or preventing hepatocyte death. They are further useful for treating osteoarthritis or rheumatoid arthritis, or CNS-related diseases.
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Page/Page column 105; 106
(2019/08/26)
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- Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors
-
Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure-activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, β5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.
- Li, Daqiang,Zhang, Xiaotuan,Ma, Xiaodong,Xu, Lei,Yu, Jianjun,Gao, Lixin,Hu, Xiaobei,Zhang, Jiankang,Dong, Xiaowu,Li, Jia,Liu, Tao,Zhou, Yubo,Hu, Yongzhou
-
p. 9177 - 9204
(2018/10/24)
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- Straightforward synthesis of fluorinated amino acids by Michael addition of ethyl bromodifluoroacetate to α,β-unsaturated α-amino acid derivatives
-
Copper-mediated Michael addition of ethyl bromodifluoroacetate to N-protected α,β-unsaturated α-amino acid esters was applied for straightforward synthesis of γ,γ-difluorinated analogues of glutamic acid (compound 1) and glutamine (compound 10). Moreover, a proline-based, sterically constrained analog of γ,γ-difluoroglutamic acid (compound 24) was prepared.
- Kondratov, Ivan S.,Bugera, Maxym Ya.,Tolmachova, Nataliya A.,Daniliuc, Constantin G.,Haufe, Günter
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p. 100 - 108
(2018/05/09)
-
- Antimicrobial Compounds
-
An antimicrobial compound, as well as the salts, derivatives and analogues thereof, said compound being represented by the general formula (I): wherein R1 represents a peptide part P1 or a peptide part P2.
- -
-
Paragraph 0114; 0115; 0171; 0172
(2017/08/26)
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- New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
-
A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
- Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
-
supporting information
p. 2127 - 2132
(2017/10/31)
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- Stereoselective synthesis of lanthionine derivatives in aqueous solution and their incorporation into the peptidoglycan of Escherichia coli
-
The three diastereoisomers - (R,R), (S,S) and meso - of lanthionine were synthesized in aqueous solution with high diastereoselectivity (>99%). The (S) and (R) enantiomers of two differently protected sulfamidates were opened by nucleophilic attack of (R) or (S)-cysteine. Acidification and controlled heating liberated the free lanthionines. Using the same chemistry, an α-benzyl lanthionine was also prepared. The proposed method, which avoids the need of enrichment by recrystallization, opens the way to the labelling of these compounds with 35S. Furthermore, in vivo bioincorporation into Escherichia coli W7 was studied. No incorporation of α-benzyl lanthionine was observed. In contrast, meso-lanthionine can effectively replace meso-diaminopimelic acid in vivo, while in the presence of (R,R)-lanthionine the initial increase of bacterial growth was followed by cell lysis. In the future, meso-[35S]lanthionine could be used to study the biosynthesis of peptidoglycan and its turnover in relation to cell growth and division.
- Denoel, Thibaut,Zervosen, Astrid,Gerards, Thomas,Lemaire, Christian,Joris, Bernard,Blanot, Didier,Luxen, Andre
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p. 4621 - 4628
(2014/10/16)
-
- Synthesis of a novel tetrafluoropyridine-containing amino acid and tripeptide
-
The synthesis of a novel fluoropyridine-containing amino acid from pentafluoropyridine by a nucleophilic substitution process is reported. The orthogonal protecting groups can be manipulated and the fluoropyridine amino acid incorporated into a tripeptide
- Hudson, Alex S.,Hoose, Alex,Coxon, Christopher R.,Sandford, Graham,Cobb, Steven L.
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p. 4865 - 4867
(2013/09/02)
-
- Microwave-assisted benzyl-transfer reactions of commercially available 2-benzyloxy-1-methylpyridinium triflate
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Benzylation of alcohols and other substrates under thermal conditions translates smoothly from conventional heating into MW-assisted organic synthesis (MAOS). Reactions times are decreased from hours to minutes while good to excellent yields are maintained. MW heating should be considered for benzylation of high-value substrates using the title reagent.
- Wang, Teng-Wei,Intaranukulkit, Tanit,Rosana, Michael R.,Slegeris, Rimantas,Simon, Janet,Dudley, Gregory B.
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supporting information; experimental part
p. 248 - 250
(2012/02/04)
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- A fluorogenic probe for the catalyst-free detection of azide-tagged molecules
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Fluorogenic reactions in which non- or weakly fluorescent reagents produce highly fluorescent products can be exploited to detect a broad range of compounds including biomolecules and materials. We describe a modified dibenzocyclooctyne that under catalyst-free conditions undergoes fast strain-promoted cycloadditions with azides to yield strongly fluorescent triazoles. The cycloaddition products are more than 1000-fold brighter compared to the starting cyclooctyne, exhibit large Stokes shift, and can be excited above 350 nm, which is required for many applications. Quantum mechanical calculations indicate that the fluorescence increase upon triazole formation is due to large differences in oscillator strengths of the S0 S 1 transitions in the planar C2v-symmetric starting material compared to the symmetry-broken and nonplanar cycloaddition products. The new fluorogenic probe was successfully employed for labeling of proteins modified by an azide moiety.
- Friscourt, Frederic,Fahrni, Christoph J.,Boons, Geert-Jan
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supporting information
p. 18809 - 18815
(2013/01/15)
-
- Stable triazolylphosphonate analogues of phosphohistidine
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Histidine-phosphorylated proteins and the corresponding kinases are important components of bacterial and eukaryotic cell-signalling pathways, and are therefore potential drug targets. The study of these biomolecules has been hampered by the lability of the phosphoramidate functional group in the phosphohistidines and the lack of generic antibodies. Herein, the design and concise synthesis of stable triazolylphosphonate analogues of N1-and N3-phosphohistidine, and derivatives suitable for bioconjugation, are described. Springer-Verlag 2011.
- Mukai, Shin,Flematti, Gavin R.,Byrne, Lindsay T.,Besant, Paul G.,Attwood, Paul V.,Piggott, Matthew J.
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experimental part
p. 857 - 874
(2012/10/07)
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- A facile synthesis of the spiroindoline-based growth hormone secretagogue, MK-677
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A facile and improved route for the synthesis of the orally active spiroindoline-based growth hormone secretagogue, MK-677 was described. The key step adopted the Fischer indole/reduction strategy. The preparation of the key intermediates N-protected piperidine carboxaldehyde 5 and the N-Boc-O-benzyl-d-serine (2) are also optimized.
- Qi, Xian Liang,Yang, Er Qun,Zhang, Jun Tao,Wang, Tao,Cao, Xiao Ping
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p. 661 - 664
(2012/07/03)
-
- Efficient synthesis of benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-ω- iodoalkanoates
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The efficient synthesis of four benzyl 2-(S)-[(tert-butoxycarbonyl)amino]- ω-iodoalkanoates {benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-3- iodopropanoate, benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-4-iodobutanoate, benzyl 2-(S)-[(tert-butoxycarbonyl)amino]-
- Koseki, Yohei,Yamada, Haruka,Usuki, Toyonobu
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p. 580 - 586
(2011/06/21)
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- New reagents for the synthesis of arylmethyl ethers and esters
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This Account chronicles efforts leading up to the development of new arylmethyl transfer (benzylation) reagents for protecting oxygen functional groups under relatively mild and neutral conditions. It begins with an investigation of organosiletanes as surrogate hydroxyl groups, which inspired siletane-functionalized benzyl ethers and forced us to confront the difficulties associated with the synthesis of benzyl ethers. The end result is a new series of neutral oxypyridinium salts for the benzylation of various nucleophilic functional groups under mild conditions. 1 Introduction 2 Tamao-type Oxidation of Strained Organosiletanes 3 p-Siletanylbenzyl (PSB) Protecting Groups 4 2-Benzyloxy-1-methylpyridinium Triflate 5 Friedel-Crafts Reactions and Mechanistic Insights 6 Benzyl Ester Formation 7 Substituted Benzyl Transfer Reagents 8 Conclusions and Outlook. Georg Thieme Verlag Stuttgart New York.
- Albiniak, Philip A.,Dudley, Gregory B.
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scheme or table
p. 841 - 851
(2010/07/10)
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- Synthesis of benzyl esters using 2-benzyloxy-1-methylpyridinium triflate
-
(Chemical Equation Presented) Triethylamine (Et3N) mediates esterification reactions between the title reagent (1) and carboxylic acids. Alcohols, phenols, amides, and other sensitive functionality are not affected; a dual role for Et3N as a promoter and a scavenger is postulated. Benzyl esters are obtained from substrates including amino acid and sugar derivatives.
- Tummatorn, Jumreang,Albiniak, Philip A.,Dudley, Gregory B.
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p. 8962 - 8964
(2008/03/12)
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- Design, synthesis, and biological activity of novel triazole amino acids used to probe binding interactions between ligand and neutral amino acid transport protein SN1
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Novel triazole amino acids were synthesized as probes to investigate ligand-protein binding interactions of the neutral amino acid transporter SN1. The bonding hypothesis to be tested was that the side chains of endogenous substrates are acting as H-bond acceptors. Although limited inhibition of 3H-l-glutamine uptake by SN1 expressing oocytes was observed, the synthetic compounds show a trend that suggests a hydrogen bond interaction just outside the endogenous ligand binding pocket.
- Gajewski, Mariusz,Seaver, Ben,Esslinger, C. Sean
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p. 4163 - 4166
(2008/03/11)
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- ORALLY AVAILABLE SPHINGOSINE 1-PHOSPHATE RECEPTOR AGONISTS AND ANTAGONISTS
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The present invention relates to S1P analogs that have activity as S1Preceptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure (I) wherein R11 is C5-C18 alkyl or C5-C18 alkenyl; Q is selected from the group consisting of C3-C6 optionally substituted cycloalkyl, C3-C6 optionally substituted heterocyclic, C3-C6 optionally substituted aryl C3-C6 optionally substituted heteroaryl and; R2 is selected from the group consisting of H, C1-C4 alkyl, (C1-C4 alkyl)OH and (C1-C4 alkyl)NH2; R23 is H or C1-C4 alkyl, and R15 is a phosphonate ester or a phosphate ester or a pharmaceutically acceptable salt or tautomer thereof.
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Page/Page column 94; 102-103
(2008/06/13)
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- Synthesis of Para-alkyl aryl amide analogues of sphingosine-1-phosphate: Discovery of potent S1P receptor agonists
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Sphingosine-1-phosphate (S1P) is a biologically active lysophospholipid with the capacity to induce a broad range of cellular responses via its interaction with the S1P family of G-protein coupled receptors. This report describes the synthesis of several
- Clemens, Jeremy J.,Davis, Michael D.,Lynch, Kevin R.,Macdonald, Timothy L.
-
p. 3401 - 3404
(2007/10/03)
-
- Reverse-turn mimetics and composition and methods relating thereto
-
Conformationally constrained compounds that mimic the secondary structure of reverse-turn regions of biologically active peptides and proteins having the following structure are disclosed: 1 wherein A, R1, R2, R2a and R3 are as defined herein. Such compounds have utility over a wide range of fields, including use as diagnostic and therapeutic agents. In particular, compounds of this invention are useful in pharmaceutical compositions as anti-inflammatory agents as well as inhibitors of central nervous disorders. Libraries containing the compounds of this invention are also disclosed, as well as methods for screening the same to identify biologically active members.
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-
- Polymer-supported O-benzyl and O-allylisoureas: Convenient preparation and use in ester synthesis from carboxylic acids
-
Polymer-supported O-methyl, O-benzyl, and O-allyl-isoureas were prepared by copper(II)-catalyzed reaction of polymer-supported carbodiimide with the corresponding alcohols. These polymer-supported reagents were successfully employed to convert a series of carboxylic acids to methyl, benzyl, or allyl esters, in good yields. The products were obtained with high purity (>95% by NMR) after a simple resin filtration-solvent evaporation sequence.
- Crosignani, Stefano,White, Peter D.,Steinauer, Rene,Linclau, Bruno
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p. 853 - 856
(2007/10/03)
-
- Application of serine- and threonine-derived cyclic sulfamidates for the preparation of S-linked glycosyl amino acids in solution- and solid-phase peptide synthesis
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Cyclic sulfamidates were synthesized in 60% yield from L-serine and allo-L-threonine, respectively. These sulfamidates reacted with a variety of unprotected 1-thio sugars in aqueous bicarbonate buffer (pH 8) to afford the corresponding S-linked serine- and threonine-glycosyl amino acids with good diastereoselectivity (≥97%) after hydrolysis of the N-sulfates. The serine-derived sulfamidate was incorporated into a simple dipeptide to generate a reactive dipeptide substrate that underwent chemoselective ligation with a 1-thio sugar to afford an S-linked glycopeptide. This sulfamidate was also incorporated into a peptide on a solid support in conjunction with solid-phase peptide synthesis. Chemoselective ligation of a 1-thio sugar with the cyclic sulfamidate was achieved on the solid support, followed by removal of the N-sulfate. Finally, the peptide chain of the resulting support-bound S-linked glycopeptide was extended using standard peptide synthesis procedures.
- Cohen, Scott B.,Halcomb, Randall L.
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p. 2534 - 2543
(2007/10/03)
-
- Soluble alpha-amino acid salts in acetonitrile: practical technology for the production of some dipeptides.
-
Alpha-amino acids are soluble in acetonitrile when treated with phosphazene bases. As a result, the protection/deprotection events that are usually required for peptide coupling reactions can be minimized. This is illustrated in the synthesis of the important angiotensin-converting enzyme (ACE) inhibitor enalapril. [reaction: see text]
- Palomo, Claudio,Palomo, Antonio L,Palomo, Francisco,Mielgo, Antonia
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p. 4005 - 4008
(2007/10/03)
-
- Selective nitrolytic deprotection of N-BOC-amines and N-BOC-amino acids derivatives
-
The extension of the deprotection procedure using HNO3 in CH2Cl2 to a number of appropriately selected N-BOC-masked amines and derivatives of natural amino acids was investigated. The method was found to work effectively with almost all tested substrates, with the exception of activated aromatic amines and heterocycles which underwent unavoidable faster oxidation. Alanine, phenylalanine, serine and lysine derivatives were efficiently deprotected, as well as dipeptide Ala-Phe, preserving the configuration of the substrates and without affecting copresent Z and ester functions, with a remarkable selectivity towards acid sensitive t-butyl esters. The obtained amino acids esters, isolated and characterized in the form of nitrates salts, proved to be suitable intermediates to be used in peptide synthesis.
- Strazzolini, Paolo,Melloni, Tiziana,Giumanini, Angelo G
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p. 9033 - 9043
(2007/10/03)
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- Synthesis of L-selenocystine, L-[77Se]selenocystine and L-tellurocystine
-
Synthetic routes for the synthesis of stable isotope labelled amino acids which contain either a selenium or a tellurium atom have been explored. L-Selenocystine, L-[77Se]selenocystine and L-tellurocystine have been constructed in four steps from commercially available methyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-hydroxypropionate. The sequence of reactions has been successfully scaled up giving significant quantities of the chalcogen based amino acids in fair to good overall yield. Copyright 1997 by the Royal Society of Chemistry.
- Stocking, Emily M.,Schwarz, Jessie N.,Senn, Hans,Salzmann, Michael,Silks, Louis A.
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p. 2443 - 2447
(2007/10/03)
-
- Peptide Synthesis in Aqueous Solution. V. Properties and Reactivities of (p-Hydroxyphenyl)benzylmethylsulfonium Salts for Direct Benzyl Esterification of N-Acylpeptides
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Some (p-hydroxyphenyl)benzylmethylsulfonium salts were prepared. These compounds generated a benzyl cation and converted not only N-acylamino acids but also N-acylpeptides into their corresponding benzyl esters without causing the racemization.
- Nakata, Takashi,Nakatani, Masaru,Takahashi, Masatoshi,Okai, Jiro,Kawaoka, Yoshiaki,Kouge, Katsushige,Okai, Hideo
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p. 1099 - 1106
(2007/10/03)
-
- Synthesis of an enantiomerically pure serine-derived thiazole
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Previously reported methods for preparing enantiomerically pure thiazoles are inadequate for the synthesis of inherently labile O-alkyl serine-derived thiazoles. The intermediate N-Boc-(O-methylseryl) thiazolines are very susceptible to tautomerization, e
- Sowinski, Jennifer A.,Toogood, Peter L.
-
p. 7671 - 7676
(2007/10/03)
-
- Wittig reaction with N-protected 3-(triphenylphosphonio)alaninates: Synthesis of optically active (E)-(2-arylvinyl)glycine derivatives
-
(R)-[2-Carboxy-2-[(methoxycarbonyl)amino]ethyl]triphenylphosphonium chloride (1) was converted by treatment with anion exchange resin (HCO3-) into the inner salt 13h, which gave a better yield (43%) than 1 in the Wittig reaction with benzaldehyde to afford the [S-(E)]-(2-phenylvinyl)glycine derivative 24. The inner salt 13i bearing an N-benzyioxycarbonyl group was prepared by hydrogenolysis of (R)-[3-benzyloxy-2-[(benzyloxycarbonyl)amino]-3-oxopropyl]triphenylpho sphonium chloride (11e) over palladium on carbon, followed by dehydrochlorination. Hydrogenolysis of 11e over Pearlman's catalyst afforded the unprotected phosphonium chloride 12 (X = Cl). N-tert-Butoxycarbonylation of 12 followed by dehydrochlorination afforded 13j, which was more efficiently prepared through hydrogenolysis of (R)-[3-benzyloxy-2-[(tert-butoxycarbonyl)amino]-3-oxopropyl]triphenylp hosphonium chloride (11f). The usefulness of 13h-j as building blocks for the synthesis of configurationally labile (2-arylvinyl)glycine derivatives was exemplihed by the Wittig reactions with piperonal, which exclusively afforded the (E)-isomers 18h-j with high optical purity in 28-39% yield.
- Itaya,Iida,Shimizu,Mizutani,Morisue,Sugimoto,Tachinaka
-
p. 252 - 261
(2007/10/02)
-
- The synthesis of chiral 3-oxo-6-[(phenylmethoxy)-carbonyl]-2-piperazineacetic acid esters designed for the presentation of an aspartic acid side chain. A subsequent novel Friedel Crafts reaction
-
The syntheses of (2S, 6R)-, and (2S, 6S)-3-oxo-6-[(phenylmethoxy)carbonyl]-2-piperazineacetic acid methyl esters from L- or D-serine and dimethyl-D-malate are described. Acylation of the (2S, 6S) isomer with 3-methoxyphenylacetyl chloride, hydrogenolysis of the benzyl ester, followed by treatment with oxalyl chloride then aluminum chloride led to an unexpected tricyclic product into which a C2O2 unit had been incorporated.
- Kogan,Rawson
-
p. 7089 - 7092
(2007/10/02)
-
- Preparation of Enantiomerically Pure Protected 4-Oxo-α-amino Acids and 3-Aryl-α-amino Acids from Serine
-
The organozinc reagent 13, prepared from the protected β-iodo alanine derivative 3c using ultrasonic activation, is efficiently acylated using acid chlorides in the presence of bis(triphenylphosphine)palladium dichloride to give enantiomerically pure protected 4-oxo-α-amino acids 17 in 39-90percent yield (13 examples).Zinc reagent 13 can also be coupled with aryl iodides in the presence of bis(tri-o-tolylphosphine)palladium dichloride to give enantiomerically pure protected phenylalanine analogues 26, 29, and 30 in 10-67percent yield (11 examples).The reaction tolerates the presence of a variety of functional groups in the acid chloride and the aryl iodide and provides derivatives which can be easily deprotected, at either the carboxyl or amino terminus, to give intermediates suitable for peptide synthesis.
- Jackson, Richard F. W.,Wishart, Neil,Wood, Anthony,James, Keith,Wythes, Martin J.
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p. 3397 - 3404
(2007/10/02)
-
- Glycosylated analogs of somatostatin
-
Somatostatin (SS) is modified to incorporate a carbohydrate moiety in the peptide chain by linkage to either Asn, Ser or Thr. The modified SS peptide analog may have the formula: STR1 wherein R1 is preferably a hexose or amino-hexose, such as glucose or N-acetylglucosamine. Alternatively, the carbohydrate can be linked to Ser or Thr by an ether bond. Such glycosomatostatins have an extended biological half-life compared to the parent peptide and substantially the same potency. Modifications and substitutions with respect to other amino acid residues in the chain can be made in the glycopeptides, for the purpose of increasing the effectiveness of SS analogs in other ways, and such increased effectiveness is a characteristic of the glycosomatostatin along with its longer-acting biological effect.
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- SYNTHESIS OF A GLYCOTRIPEPTIDE AND A GLYCOSOMATOSTATIN CONTAINING THE 3-O-(2-ACETAMIDO-2-DEOXY-β-D-GLUCOPYRANOSYL)-L-SERINE RESIDUE
-
3-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-N-(tert-butyloxycarbonyl)-L-serine was synthesized and condensed by the solid-phase procedure to give the sequence Gly-3)-Ser>-Ala-OH and β-D-GlcpNAc-(1->3)-Ser-13-somatostat
- Lavielle, Solange,Ling, Nicolas C.,Saltman, Robert,Guillemin, Roger C.
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p. 229 - 236
(2007/10/02)
-