- A NOVEL AND EFFICIENT SYNTHESIS OF L-VINYLGLYCINE
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A simple and practical synthesis of the title compound starting with L-glutamic acid is described.
- Hanessian, Stephen,Sahoo, Soumya P.
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Read Online
- Kras inhibitory cyclic peptide compound
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The following were discovered: a cyclic peptide compound that interacts with Ras; and an unnatural amino acid that is useful in the production of said cyclic peptide compound. The cyclic peptide compound was also discovered to inhibit bonding between Ras and SOS. The following were additionally discovered: a specific unnatural amino acid included in said cyclic peptide compound; and a manufacturing method therefor.
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Paragraph 0362; 0656-0657
(2021/06/03)
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- PROCESSES FOR PREPARATION OF (S)-TERT-BUTYL 4,5-DIAMINO-5-OXOPENTANOATE
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Provided are processes for the preparation of (S)-tert-butyl 4,5-diamino-5-oxopentanoate, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof. Also provided are solid forms of various intermediates and products obtained from the processes.
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- Versatile synthesis of the signaling peptide glorin
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We present a versatile synthesis of the eukaryotic signaling peptide glorin as well as glorinamide, a synthetic analog. The ability of these compounds to activate glorin-induced genes in the social amoeba Polysphondylium pallidum was evaluated by quantita
- Barnett, Robert,Raszkowski, Daniel,Winckler, Thomas,Stallforth, Pierre
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supporting information
p. 247 - 250
(2017/03/14)
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- Synthesis of N -[(3 S)-2,6-dioxo-1-(2-phenylethyl)-3-piperidinyl]-(2 S)-2-methylbutanamide (( - )-julocrotine)
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The total synthesis of ( - )-julocrotine (1) starting from l-glutamic acid in 41% overall yield is described. The methodology utilizes protection, deprotection, and regioselection (carbonyl differentiation via oxazolidinone) protocols, and glutarimide ring formation is the key step.
- Silva, Luciano L.,Joussef, Antonio C.
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p. 1531 - 1534
(2011/08/21)
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- New developments for the design, synthesis and biological evaluation of potent SARS-CoV 3CLpro inhibitors
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A series of trifluoromethyl, benzothiazolyl or thiazolyl ketone-containing peptidic compounds as SARS-CoV 3CL protease inhibitors were developed and their potency was evaluated by in vitro protease inhibitory assays. Three candidates had encouraging resul
- Regnier, Thomas,Sarma, Diganta,Hidaka, Koushi,Bacha, Usman,Freire, Ernesto,Hayashi, Yoshio,Kiso, Yoshiaki
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scheme or table
p. 2722 - 2727
(2010/01/16)
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- Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors
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Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program FITTED, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light on the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.
- Lawandi, Janice,Toumieux, Sylvestre,Seyer, Valentine,Campbell, Philip,Thielges, Sabine,Juillerat-Jeanneret, Lucienne,Moitessier, Nicolas
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experimental part
p. 6672 - 6684
(2010/04/28)
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- Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors
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Trifluoromethyl-β-amino alcohol 11 [(4S)-tert-butyl 4-amino-6,6,6-trifluoro-5-hydroxyhexanoate] was synthesized in five steps starting from Cbz-l-Glu-OH 5 where the key step involved the introduction of the trifluoromethyl (CF3) group to oxazolidinone 7, resulting in the formation of silyl ether 8 [(4S,5S)-benzyl 4-(2-(tert-butoxycarbonyl)ethyl)-5-(trifluoromethyl)-5-(trimethylsilyloxy)oxazolidine-3-carboxylate]. Compound 11 was then converted into four tri- and tetra-glutamic acid and glutamine peptides (1-4) possessing a CF3-ketone group that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CLpro).
- Sydnes, Magne O.,Hayashi, Yoshio,Sharma, Vinay K.,Hamada, Takashi,Bacha, Usman,Barrila, Jennifer,Freire, Ernesto,Kiso, Yoshiaki
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p. 8601 - 8609
(2007/10/03)
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- Effective methods for the synthesis of N-methyl β-amino acids from all twenty common α-amino acids using 1,3-oxazolidin-5-ones and 1,3-oxazinan-6-ones
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N-Methyl β-amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N-methyl α-amino acids. Starting from α-amino acids, two approaches were used to prepare the corresponding N-methyl β-amino acids. First, α-amino acids were converted to N-methyl α-amino acids by the so-called '1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt-Eistert procedure to afford N-protected N-methyl β-amino acids derived from the 20 common α-amino acids. These compounds were prepared in yields of 23-57% (relative to N-methyl α-amino acid). In a second approach, twelve N-protected α-amino acids could be directly homologated by the Arndt-Eistert procedure, and the resulting β-amino acids were converted to the 1,3-oxazinan-6-ones in 30-45% yield. Finally, reductive cleavage afforded the desired N-methyl β-amino acids in 41-63% yield. One sterically congested β-amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N-methyl β-amino acid 61 in 71% yield (Scheme 2). Thus, our protocols allow the ready preparation of all N-methyl β-amino acids derived from the 20 proteinogenic α-amino acids.
- Hughes, Andrew B.,Sleebs, Brad E.
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p. 2611 - 2637
(2007/10/03)
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- Nγ-Aryl glutamine analogues as probes of the ASCT2 neutral amino acid transporter binding site
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Analogues of l-glutamine were designed and synthesized to test a hydrogen-bond hypothesis between ligand and neutral amino acid transporter ASCT2. The key design feature contains a substituted phenyl ring on the amide nitrogen that contains electron withdrawing and electron donating groups that alter the pKa of the amide NH. Through this study a preliminary binding site map has been developed, and a potent commercially available competitive inhibitor of the ASCT2 transporter has been identified.
- Esslinger, C. Sean,Cybulski, Kimberly A.,Rhoderick, Joseph F.
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p. 1111 - 1118
(2007/10/03)
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- Improved synthesis of 7,5-fused bicyclic lactams for use as peptidomimetics
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An improved synthesis of (3S, 7R, 10S)-methyl-2-oxo-3-N-phthaloylamino-1- azabicyclo[5.3.0]decane-10-carboxylate from L-glutamic acid and L-allylglycine is presented.
- Seide, Wesly,Watson, Samuel E.
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p. 995 - 1002
(2007/10/03)
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- Biosynthesis of 4-methylproline in cyanobacteria: Cloning of nosE and nosF genes and biochemical characterization of the encoded dehydrogenase and reductase activities
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The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of cyanobacteria was investigated on the genetic and enzymatic level. Two genes involved in the biosynthesis were cloned and the corresponding enzymes, a zinc-dependent long-chain dehydrogenase and a Δ1-pyrroline-5-carboxylic acid (P5C) reductase homologue, were overexpressed in Escherichia coli and biochemically characterized. Putative substrates were synthesized to test enzyme substrate specificities, and deuterium labeling studies were carried out to reveal the stereospecificities of the enzymatic reactions with respect to the substrates as well as to the coenzymes.
- Luesch, Hendrik,Hoffmann, Dietmar,Hevel, Joan M.,Becker, Julia E.,Golakoti, Trimurtulu,Moore, Richard E.
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- THIAZOLIDINE DERIVATIVES
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An object of the present invention is to provide novel thiazolidine derivatives which are useful as drugs. The thiazolidine derivatives according to the present invention are compounds represented by the following general formula [I] and salts thereof, wherein R 1is alkyl, hydroxy, alkoxy, alkoxyalkyl, phenyl, phenylalkyl, phenylalkoxy, phenoxy, phenoxyalkyl, amino, alkylamino or a nonaromatic heterocycle; R 2is H or alkyl; R 3is H, alkyl or phenyl; R 4is H or alkyl; R 5is alkyl, halogenoalkyl, hydroxy, alkoxy, phenyl, phenylalkoxy, phenoxy, carboxyl, alkoxycarbonyl, phenylalkoxycarbonyl or an aromatic heterocycle; A 1is alkylene; and A 2is alkylene.
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- Synthesis of muramyl peptides containing meso-diaminopimelic acid
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Chain-extension of L-glutamate aldehyde 3 by means of the Wittig-Horner reaction furnished the desired C7 dicarboxylic acid derivative, which in turn, after C-C double bond hydrogenation and protecting group manipulation, afforded the 2,6-diaminopimelic acid derivatives (S,R)-9 and (S,S)-9, both with the desired orthogonal protecting group pattern. Synthesis of the muramic acid derivative 15 and attachment of an L-alanine residue furnished muramyl-L-alanine 18. The corresponding 1,6-anhydromuramic acid derivative 26 was obtained similarly. Treatment of these compounds with peptides 28-30 and with the 2,6-diaminopimelic acid containing di- and tripeptides 32a, 32b, and 35 gave the protected muramyl peptides 17, 37, 40, 42, 44, 46, and 49a and 49b, which, after deprotection, afforded the desired target molecules muramyl-L-alanine (38), muramyl-L-alanyl-D-glutamic acid (39), muramyl-L-alanyl-D-glutaminide (41), muramyl-L-alanyl-D- isoglutaminyl-L-lysine (43), muramyl-L-alanyl-D-isoglutaminyl-(2S,6R)-2,6-diaminopimelic acid (45), muramyl-L-alanyl- L-isoglutaminyl-(2S,6R)-2,6-diaminopimelic-D-alanme (47), 1,6-anhydromuramyl-L-alanyl-D-isoglutaminyl-(2S,6R)-2,6-diaminopimelic acid (50a), and 1,6-anhydromuramyl-L-alanyl-D- isoglutaminyl-(2S,6S)-2,6-diaminiopimelic acid (50b). ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).
- Kubasch, Niels,Schmidt, Richard R.
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p. 2710 - 2726
(2007/10/03)
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- Synthesis of (S)-2-amino-8-oxodecanoic acid (Aoda) and apicidin A
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The synthesis of (S)-2-amino-8-oxodecanoic acid, a constituent of the cyclic tetrapeptides, the apicidins, was accomplished under photolytic conditions in the presence of tri-n-butyltin hydride using glutamic acid. This enabled a total synthesis of apicidin A to be completed.
- Mou, Liyuan,Singh, Gurdial
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p. 6603 - 6606
(2007/10/03)
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- Modified Trityl Ester Protecting Groups in Peptide Synthesis
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The novel, sterically demanding heptafluorotrityl- and phenylfluorenyl ester protecting groups were developed for the pro tection of the γ-carboxy group of glutamic acid. These trityl-type protecting groups exhibit a markedly increased stability compared to triphenylmethyl esters, and in addition the very mild cleavage conditions make their selective removal in the presence of other acid labile protecting groups such as tBu possible.
- Loehr, Birgit,Orlich, Simone,Kunz, Horst
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p. 1136 - 1138
(2007/10/03)
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- Angiotensin II analogues encompassing 5,9- and 5,10-fused thiazabicycloalkane tripeptide mimetics
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A simple experimental procedure on solid phase for the construction of new tripeptidic 5,9- and 5,10-fused thiazabicycloalkane scaffolds that adopt β-turns has been developed. This N-terminal-directed bicyclization, relying on masked aldehyde precursors d
- Johannesson, Petra,Lindeberg, Gunnar,Tong, Weimin,Gogoll, Adolf,Synnergren, Barbro,Nyberg, Fred,Karlén, Anders,Hallberg, Anders
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p. 4524 - 4537
(2007/10/03)
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- The invention of radical reactions. Part 39. The reaction of white phosphorus with carbon-centered radicals. An improved procedure for the synthesis of phosphonic acids and further mechanistic insights
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White phosphorus in tetrahydrofuran under argon reacts in a long radical chain reaction with carbon radicals derived from Barton PTOC esters. The reaction is initiated by traces of oxygen and strongly inhibited by TEMPO. From the duration of the induction period the chain length can be measured as approximately one million. Each P4 molecule can add up to two carbon radicals. Oxidation of the adducts provides a convenient synthesis of phosphonic acids in high yield. With H2O2 at 0°C oxidation to the appropriate phosphinic acids is fast. For sensitive natural products the further transformation to phosphonic acids is best carried out at room temperature with an excess of SO2. In this way even linoleic acid can be convened to the corresponding phosphonic acid in good yield without any attack on the skipped diene unit. TEMPO is also remarkable for its stabilization of white phosphorus in solution when exposed to oxygen. Likewise an ordinary phosphine, like tributyl phosphine, is also stabilized by small amounts of TEMPO.
- Barton, Derek H. R.,Vonder Embse, Richard A.
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p. 12475 - 12496
(2007/10/03)
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- DIAZEPINE CONTAINING DUAL ACTION INHIBITORS
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Compounds of the formula STR1 wherein: STR2 A is are dual inhibitors of NEP and ACE. Compounds wherein A is STR3 are selective ACE inhibitors.
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- Homochiral synthesis of an aza analogue of S-adenosyl-L-methionine (AdoMet) and its binding to the E. coli methionine repressor protein (MetJ)
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A synthesis of 5′-{N-[(S)-3-amino-3-carboxypropyl]-methylamino}-5′-deoxyadenosine from D-adenosine and (S)-glutamic acid is described; this product, AzaAdoMet 2, has a pKa of 7.10 for the tertiary amino group and so acts as a charge-switchable
- Thompson, Mark J.,Mekhalfia, Abdelaziz,Jakeman, David L.,Phillips, Simon E. V.,Phillips, Kathryn,Porter, Jonathan,Blackburn, G. Michael
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p. 791 - 792
(2007/10/03)
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- Synthesis of an Aza-Analogue of S-Adenosyl-L-methionine and Its Binding to the E. coli Methionine Repressor Protein (MetJ)
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Synthesis of 5'-methylamino>-5'-deoxyadenosine is described from D-adenosine and (S)-glutamic acid.This product, AzaAdoMet 2, has a pKa of 7.10 for the tertiary amino group and so acts as a charge-switshable anal
- Thompson, Mark J.,Mekhalfia, Abdelaziz,Jakeman, David L.,Phillips, Simon E. V.,Phillips, Kathryn,et al.
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p. S85 - S87
(2007/10/03)
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- AN ASYMMETRIC SYNTHESIS OF DIFFERENTIALLY PROTECTED MESO-2,6-DIAMINOPIMELIC ACID
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Differentially protected meso-2,6-diaminopimelic acid, a component of bacterial cell walls, a biosynthetic precursor of L-lysine and a constituent of several synthetic immunostimulants, has been prepared stereospecifically from L-glutamic acid.
- Holcomb, Ryan C.,Schow, Steven,Ayral-Kaloustian, S.,Powell, Dennis
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p. 7005 - 7008
(2007/10/02)
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- Total synthesis of (+)-porothramycin B
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The first total synthesis of (+)-porothramycin B (1b is described. Our synthetic pathway can be readily applied to the synthesis of other members of the pyrrolo[1,4]benzodiazepine antibiotics.
- Fukuyama, Tohru,Liu, Gang,Linton, Steven D.,Lin, Shao-Cheng,Nishino, Hiroshi
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p. 2577 - 2580
(2007/10/02)
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- Regioselective amidation of aspartic and glutamic acid
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The synthesis of N-protected aspartic 1-amide and glutamic 1-amide from aspartic and glutamic acids via regioselective amidation of intermediate 5-oxazolidinone derivatives with aqueous ammonia or amine is described.
- Lee,Kim,Ko,Kim
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p. 935 - 936
(2007/10/02)
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- TERT-BUTYL ESTERS OF N-PROTECTED AMINO ACIDS WITH TERT-BUTYL FLUOROCARBONATE (Boc-F)
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Tert-butyl fluorocarbonate (Boc-F) is efficiently used for the synthesis of tert-butyl esters of N-protected amino acids.The reaction proceeds at room temperature and under mild conditions in the presence of triethylamine and 4-dimethylamino-pyridine.
- Loffet, A.,Galeotti, N.,Jouin, P.,Castro, B.
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p. 6859 - 6860
(2007/10/02)
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- A Convenient Differential Protection Strategy for Functional Group Manipulation of Aspartic and Glutamic Acids
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Procedures are provided for selective protection of the α-carboxyl groups of aspartic and glutamic acids via the 5-oxazolidinones 2.A convenient synthesis of a differentially protected derivative of (S)-2,3-diaminopropanoic acid, 3, is described, along wi
- Scholtz, John M.,Bartlett, Paul A.
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p. 542 - 544
(2007/10/02)
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- L-α-AMINOADIPIC ACID FROM L-GLUTAMIC ACID
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A convenient procedure for the preparation of L-α-aminoadipic acid from L-glutamic acid is described.
- Pellicciari, Roberto,Natalini, Benedetto,Marinozzi, Maura
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p. 1707 - 1714
(2007/10/02)
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- CHIRAL SYNTHESIS OF 5-HYDROXY-(L)-PIPECOLIC ACIDS FROM (L)-GLUTAMIC ACID
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A stereo- and enantio-specific synthesis of the naturally occuring cis-5-hydroxy-(L)-pipecolic acid (3) is described, starting from Z-(L)-glutamic acid; the key step involves cyclisation of a protected chlorohydrin, and also gives access to trans-5-hydroxy-(L)-pipecolic acid.
- Bailey, Patrick D.,Bryans, Justin S.
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p. 2231 - 2234
(2007/10/02)
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- CONSTITUENTS OF MICROBIAL IRON CHELATORS. THE SYNTHESIS OF OPTICALLY ACTIVE DERIVATIVES OF δ-N-HYDROXY-L-ORNITHINE.
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δ-N-Hydroxy-L-ornithine derivatives were synthesized from L-glutamic acid by reduction of the γ-acid chloride to the aldehyde, formation of the substituted oxime, and reductive acylation
- Lee, Byung Hyun,Miller, Marvin J.
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p. 927 - 930
(2007/10/02)
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