cas 59279-60-6, (R)-N-Boc-glutamic acid-1,5-dimethyl ester

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Synthesis of Imidazole and Histidine-Derived Cross-Linkers as Analogues of GOLD and Desmosine
Amino acid derivatives with a central cationic heterocyclic core (e.g., imidazolium) are biologically relevant cross-linkers of proteins and advanced glycation end (AGE) products. Here, imidazolium-containing cross-linkers were synthesized from imidazole or histidine by N-alkylation employing aspartate- and glutamate-derived mesylates as key step. Biological investigations were carried out to probe the biocompatibility of these compounds.
Sch?del, Nicole,Icik, Esra,Martini, Maike,Altevogt, Luca,Ramming, Isabell,Greulich, Andreas,Baro, Angelika,Bilitewski, Ursula,Laschat, Sabine
supporting information
p. 2260 - 2268
(2021/03/04)

L-glutamic acid derivative and synthesis method and application thereof
The invention belongs to the technical field of synthesis of medical and traditional Chinese medicine intermediates, and discloses an L-glutamic acid derivative and a synthesis method and applicationthereof. All the steps in the synthesis method are simple and in order , the obtained L-dimethyl glutamate hydrochloride oily matter is directly put into the next step of reaction through a one-pot method, L-dimethyl glutamate hydrochloride solids do not need to be obtained, the use of all the raw materials can be effectively reduced, and the cost is reduced; ethyl acetate is selected as a reaction solvent and can be effectively recycled, the utilization rate of the ethyl acetate is remarkably increased, and pollution to the environment is reduced; a final product is obtained in a crystallization manner so that the convenience and the storage convenience during transportation are improved, and the quality and the yield of the product can be further improved. The technical scheme of the synthesis method is complete and simple, the produced product is high in crystallization yield and better in quality, the overall yield of the product is conveniently, rapidly, scientifically and effectively increased to 85% or above, and raw materials are provided for research and development of new drugs.
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Paragraph 0044; 0048-0052; 0056; 00060-0064; 0066; 0070-0074

(2020/11/01)

Selenolysine: A New Tool for Traceless Isopeptide Bond Formation
Despite their biological importance, post-translationally modified proteins are notoriously difficult to produce in a homogeneous fashion by using conventional expression systems. Chemical protein synthesis or semisynthesis offers a solution to this problem; however, traditional strategies often rely on sulfur-based chemistry that is incompatible with the presence of any cysteine residues in the target protein. To overcome these limitations, we present the design and synthesis of γ-selenolysine, a selenol-containing form of the commonly modified proteinogenic amino acid, lysine. The utility of γ-selenolysine is demonstrated with the traceless ligation of the small ubiquitin-like modifier protein, SUMO-1, to a peptide segment of human glucokinase. The resulting polypeptide is poised for native chemical ligation and chemoselective deselenization in the presence of unprotected cysteine residues. Selenolysine's straightforward synthesis and incorporation into synthetic peptides marks it as a universal handle for conjugating any ubiquitin-like modifying protein to its target.
Dardashti, Rebecca Notis,Kumar, Shailesh,Sternisha, Shawn M.,Reddy, Post Sai,Miller, Brian G.,Metanis, Norman
supporting information
p. 4952 - 4957
(2020/04/07)

Zelkovamycin is an OXPHOS Inhibitory Member of the Argyrin Natural Product Family
Natural products (NPs) are an important inspirational source for developing drugs and chemical probes. In 1999, the group of ōmura reported the constitutional elucidation of zelkovamycin. Although largely unrecognized so far, this NP displays structural s
Krahn, Daniel,Heilmann, Geronimo,Vogel, Felix C. E.,Papadopoulos, Chrisovalantis,Zweerink, Susanne,Kaschani, Farnusch,Meyer, Hemmo,Roesch, Alexander,Kaiser, Markus
supporting information
p. 8524 - 8531
(2020/07/02)

Synthesis and Biological Evaluation of a Library of AGE-Related Amino Acid Triazole Crosslinkers
Three N-Boc-protected amino acids, l-serine, l-aspartic, and l-glutamic acid, were either converted into their methyl azidoalkanoates or various alkynes via Bestmann-Ohira strategy or via reaction with propargylamine and propargyl bromide, respectively. The Cu-catalyzed click reaction provided a library of amino acid based triazoles, which were further N-methylated to triazolium iodides or deprotected and precipitated as free amino acid triazole dihydrochlorides. The biological properties of all derivatives were investigated by cytotoxicity assay (against L929 mouse fibroblasts) and broth microdilution method (E. coli ΔTolC and S. aureus). First results reveal complete inactivity for triazolium iodides with cell viabilities and microbial growths nearly 100 %, indicating them as possible analogs of advanced glycation endproducts (AGEs).
Agelidis, Nektarios,Altevogt, Luca,Baro, Angelika,Bilitewski, Ursula,Bugdayci, Bakiye,Icik, Esra,Jolly, Anthony,L?ffler, Paul,Laschat, Sabine
supporting information

(2020/09/01)

[...] compound for the preparation of a classical swine fever virus (ASFV) infection drug application (by machine translation)
The invention relates to peptide aldehyde compound I, compound II in preparation for treating swine fever virus (ASFV) infection the application of the medicament, and it also relates to various optical isomer, a pharmaceutically acceptable solvate and pr
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Paragraph 0031; 0033

(2019/11/04)

Preparation and uses of novel Michael receptor-based enterovirus 71 type inhibitor
The present invention relates to a class of novel Michael receptor-based virus 71 (EV71) 3C protease inhibitors, wherein various variables of the structure general formula (M) are defined in the specification, and the compounds effectively inhibit or block the replication of enterovirus 71. The present invention relates to discovery and applications of the compound containing the structure generalformula (M), various optical isomers, pharmaceutically active metabolites, pharmaceutically acceptable salts, solvates and prodrugs thereof in preparation of antiviral drugs for the treatment of hand-foot-mouth virus infection diseases. The invention relates to an intermediate and a synthesis method for preparing the compound having the structure general formula (M). The formula (M) is defined inthe specification.
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Paragraph 0063

(2019/10/01)

4-Iminooxazolidin-2-one as a Bioisostere of the Cyanohydrin Moiety: Inhibitors of Enterovirus 71 3C Protease
A recently reported potent inhibitor of enterovirus 71 3C protease, (R)-1, was found to have stability and potential toxicity issues due to the presence of a cyanohydrin moiety. Modifying the labile cyanohydrin moiety, by serendipity, led to the discovery of 4-iminooxazolidin-2-one-based inhibitors 4e and 4g with potent inhibitory activity and significantly improved stability. In vivo pharmacokinetic studies of 4e also demonstrated high plasma exposure and moderate half-life. These compounds have shown potential of becoming anti-EV71 drug candidates.
Ma, Yuying,Shang, Chengyou,Yang, Peng,Li, Linfeng,Zhai, Yangyang,Yin, Zheng,Wang, Binghe,Shang, Luqing
supporting information
p. 10333 - 10339
(2018/12/11)

Method for selective removal of t-butyloxycarboryl from nitrogen
The invention discloses a method for selective removal of t-butyloxycarboryl from nitrogen. According to the synthesis method, directed at a reaction substrate having t-butyloxycarboryl and another acyl protecting group on a molecular nitrogen atom, in the presence of a selectfluor reagent, reaction is carried out in a solution for selective removal of t-butyloxycarboryl and retention of another acyl protecting group. The synthesis method provided by the invention is novel and efficient, is not reported in literature, and can be widely used in total synthesis and drug intermediate synthesis.
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Paragraph 0024-0025; 0026-0028; 0047-0049

(2018/03/26)

Synthesis of 5-Cyano-Tryptophan as a Two-Dimensional Infrared Spectroscopic Reporter of Structure
A concise synthesis of protected 5-cyano-l-tryptophan (Trp5CN) has been developed for 2D IR spectroscopic investigations within either peptides or proteins. To assess the potential of differently substituted cyano-tryptophans, several model cya
Chalyavi, Farzaneh,Gilmartin, Philip H.,Schmitz, Andrew J.,Fennie, Michael W.,Tucker, Matthew J.
supporting information
p. 7528 - 7532
(2018/06/04)

Target-guided screening of fragments (TGSOF) in the discovery of inhibitors against EV-A71 3C protease
Target-guided screening of fragments (TGSOF) was developed and employed in the identification of EV-A71 3C protease (3Cpro) inhibitors. We identified 4-acetylpyridine and 3-acetylpyridine as effective P3 fragments of an inhibitor and obtained the corresponding irreversible inhibitors 12c and 12fvia this method. Furthermore, based on 12c and 12f, we have obtained reversible inhibitors 17c and 17f. These results demonstrated that TGSOF is a useful strategy for identifying suitable fragments in developing leads in drug discovery.
Fu, Shengjun,Nie, Quandeng,Ma, Yuying,Song, Ping,Ren, Xuejiao,Luo, Cheng,Shang, Luqing,Yin, Zheng
supporting information
p. 2890 - 2893
(2018/03/23)

Two Distinct Mechanisms for C-C Desaturation by Iron(II)- and 2-(Oxo)glutarate-Dependent Oxygenases: Importance of α-Heteroatom Assistance
Hydroxylation of aliphatic carbons by nonheme Fe(IV)-oxo (ferryl) complexes proceeds by hydrogen-atom (H?) transfer (HAT) to the ferryl and subsequent coupling between the carbon radical and Fe(III)-coordinated oxygen (termed rebound). Enzymes that use H?-abstracting ferryl complexes for other transformations must either suppress rebound or further process hydroxylated intermediates. For olefin-installing C-C desaturations, it has been proposed that a second HAT to the Fe(III)-OH complex from the carbon α to the radical preempts rebound. Deuterium (2H) at the second site should slow this step, potentially making rebound competitive. Desaturations mediated by two related l-arginine-modifying iron(II)- and 2-(oxo)glutarate-dependent (Fe/2OG) oxygenases behave oppositely in this key test, implicating different mechanisms. NapI, the l-Arg 4,5-desaturase from the naphthyridinomycin biosynthetic pathway, abstracts H? first from C5 but hydroxylates this site (leading to guanidine release) to the same modest extent whether C4 harbors 1H or 2H. By contrast, an unexpected 3,4-desaturation of l-homoarginine (l-hArg) by VioC, the l-Arg 3-hydroxylase from the viomycin biosynthetic pathway, is markedly disfavored relative to C4 hydroxylation when C3 (the second hydrogen donor) harbors 2H. Anchimeric assistance by N6 permits removal of the C4-H as a proton in the NapI reaction, but, with no such assistance possible in the VioC desaturation, a second HAT step (from C3) is required. The close proximity (≤3.5 ?) of both l-hArg carbons to the oxygen ligand in an X-ray crystal structure of VioC harboring a vanadium-based ferryl mimic supports and rationalizes the sequential-HAT mechanism. The results suggest that, although the sequential-HAT mechanism is feasible, its geometric requirements may make competing hydroxylation unavoidable, thus explaining the presence of α-heteroatoms in nearly all native substrates for Fe/2OG desaturases.
Dunham, Noah P.,Chang, Wei-Chen,Mitchell, Andrew J.,Martinie, Ryan J.,Zhang, Bo,Bergman, Jonathan A.,Rajakovich, Lauren J.,Wang, Bo,Silakov, Alexey,Krebs, Carsten,Boal, Amie K.,Bollinger, J. Martin
supporting information
p. 7116 - 7126
(2018/05/15)

CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.
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Paragraph 00444

(2017/09/27)

Anti-enteroviral 71(EV71) 4-iminooxazolidine-2-ketone compound as well as preparation method and application of anti-enteroviral 71(EV71) 4-iminooxazolidine-2-ketone compound
The invention discloses a 4-iminooxazolidine-2-ketone enterovirus 71(EV71) 3C protease inhibitor of which the structural general formula is shown as a compound (M), each variable in the structure is defined as the specification, and the compounds are used for effectively inhibiting or stopping the replication of enterovirus 71. The invention relates to discovery and application of a compound with a structure shown as the formula (M) as well as various optical isomers of the compound, a pharmaceutically active metabolite, a medicinal salt, a solvate and a prodrug of the compound in preparation of antiviral drugs for treating hand-foot-mouth virus infection diseases and also relates to an intermediate for preparing the compound with the structure shown as the formula (M) and a synthesis method.
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Paragraph 0084; 0085; 0086

(2018/03/24)

Synthesis method of moCys section of marine natural product apratoxin E
The invention relates to a synthesis method of moCys section of a marine natural product apratoxin E, and belongs to the field of chemical synthesis. The moCys section (C27 to C30 section) of the marine natural product apratoxin E is prepared from cheap a
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Paragraph 0011

(2017/01/19)

Expedient synthesis of (+)-lycopalhine A
Two amino acids play a key role in the first total synthesis of lycopalhine A. l-glutamic acid serves as a convenient chiral starting material for the 13-step synthesis, and l-proline promotes an unusual 5-endo-trig Mannich cyclization that generates the central pyrrolidine ring of the Lycopodium alkaloid. The bicyclo[3.3.0]octanol moiety of the molecule is formed through an intramolecular aldol addition that may occur spontaneously in nature. Just Another Mannich Monday: By using l-glutamate and l-proline as a starting material and catalyst, respectively, the complex alkaloid lycopalhine A was assembled in only 13 steps. The synthesis features not only an unusual Mannich reaction but also a biomimetic aldol addition that completes the intricate carbon skeleton of the natural product.
Williams, Benjamin M.,Trauner, Dirk
supporting information
p. 2191 - 2194
(2016/02/18)

Expeditious synthesis of enantiopure, orthogonally protected bis-α-amino acids (OPBAAs) and their use in a study of Nod1 stimulation
A convenient approach towards the synthesis of orthogonally protected chiral bis-a-amino acids (OPBAAs) is described. The key transformations include: (1) a highly stereoselective conjugation (alkylation) of the Sch?llkopf bislactim ethers and oxazolidinyl alkyl halides to build a backbone skeleton; and (2) our orthogonal protection strategy. A series of enantiopure OPBAAs bearing a variety of alkyl chain as a spacer; two stereogenic centers; and three protecting groups were prepared as examples. These versatile molecules were applied to the synthesis of biologically interesting di- or tri-peptide analogues, including chiral iE-meso-DAP and A-iE-meso-DAP, for the study of Nod1 activation in the innate immune response.
Chen, Po-Ting,Lin, Cheng-Kun,Tsai, Chih-Ju,Huang, Duen-Yi,Nien, Fu-Yao,Lin, Wan-Wan,Cheng, Wei-Chieh
supporting information
p. 474 - 482
(2015/01/30)

Cyanohydrin as an anchoring group for potent and selective inhibitors of enterovirus 71 3C protease
Cyanohydrin derivatives as enterovirus 71 (EV71) 3C protease (3Cpro) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. Compared with the reported inhibitors, cyanohydrins (1S,2S,2′S,5S)-16 and (1R,2S,2′S,5S)-16 exhibited significantly improved activity and attractive selectivity profiles against other proteases, which were a result of the specific interactions between the cyanohydrin moiety and the catalytic site of 3Cpro. Cyanohydrin as an anchoring group with high selectivity and excellent inhibitory activity represents a useful choice for cysteine protease inhibitors.
Zhai, Yangyang,Zhao, Xiangshuai,Cui, Zhengjie,Wang, Man,Wang, Yaxin,Li, Linfeng,Sun, Qi,Yang, Xi,Zeng, Debin,Liu, Ying,Sun, Yuna,Lou, Zhiyong,Shang, Luqing,Yin, Zheng
supporting information
p. 9414 - 9420
(2015/12/23)

A practical, catalytic and selective deprotection of a Boc group in N,Na?2-diprotected amines using iron(III)-catalysis
A selective, catalytic and practical method for removing a Boc group from several N,Na?2-diprotected amino acids and amine derivatives using iron(III) salts as sustainable catalysts is described. The process is clean, not needing a purification step. A th
L?3pez-Soria, Juan M.,P??rez, Sixto J.,Hern??ndez, J. Nicol??s,Ram??rez, Miguel A.,Mart??n, V??ctor S.,Padr?3n, Juan I.
p. 6647 - 6651
(2015/03/03)

The structure elucidation and total synthesis of β-lipomycin
Here we describe the synthesis of β-lipomycin, a secondary metabolite isolated from the fermentation broth of Corallococcus coralloides. The synthesis relies on the structural assignment made by a statistical method, the so-called profile hidden Markov model. Using this protocol, not only the configuration of the secondary alcohol, but also of the adjacent methyl branch could be deduced. The synthesis therefore not only provides access to this natural product but also confirms the validity of this approach for configurational assignment at methyl branches of modular polyketides.
Hartmann, Olaf,Kalesse, Markus
supporting information
p. 7335 - 7338
(2014/07/21)

TOTAL SYNTHESIS OF THAXTOMIN A ANALOGUES AND THEIR INTERMEDIATES
Improved synthetic methods for the production of thaxtomin analogues, particularly thaxtomin A, and intermediates therefore such as substituted tryptophans and in particular, 4-nitro-L-tryptophan, and substituted phenyl acrylic acids are disclosed. Bioass
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Paragraph 0026; 0027

(2014/09/30)

Synthesis of cis -5-trifluoromethylproline from l -glutamic acid
The diastereoselective synthesis of cis-5-trifluoromethylproline (5-Tfm-Pro) from l-glutamic acid is described. 5-Tfm-Pro could be obtained through a seven-step linear sequence. Trifluoromethylation of the glutamic-derived ester or aldehyde and subsequent reduction of the cyclic imine are the key steps in the synthesis. Georg Thieme Verlag Stuttgart New York.
Ortial, Stéphanie,Dave, Rajesh,Benfodda, Zohra,Bénimélis, David,Meffre, Patrick
supporting information
p. 569 - 573
(2014/03/21)

Total synthesis of thaxtomin A and its stereoisomers and findings of their biological activities
The first and facile total synthesis of thaxtomin A and its three stereoisomers has been achieved. The synthetic approach involves intramolecular nucleophilic cyclization of an amide toward a ketoamide group to produce a C-hydroxydiketopiperazine scaffold
Zhang, Hongbo,Ning, Xin,Hang, Hang,Ru, Xuyan,Li, Haichen,Li, Yonghong,Wang, Lizhong,Zhang, Xiao,Yu, Shujing,Qiao, Yuanyuan,Wang, Xin,Wang, Peng George
supporting information
p. 5670 - 5673
(2013/12/04)

TRICYCLIC HETEROCYCLIC COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF AS JAK INHIBITORS
The invention provides novel compounds of formula I having the general formula:(I) wherein Rl s R2, R3, X and Y are as described herein. Accordingly, the compounds may be provided in pharmaceutically acceptable compositions and used for the treatment of immunological or hyperproliferative disorders.
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Page/Page column 109; 110

(2013/03/26)

Kilogram synthesis of (S)-3-aminopyran from l -glutamic acid
We describe the development of a concise route to prepare kilogram quantities of (S)-3-aminopyran, a key intermediate in the synthesis of a Jak1 inhibitor. The chiral amine was introduced via a chiral-pool approach and involves using inexpensive, commerci
Savage, Scott,Babu, Srinivasan,Zak, Mark,Mao, Zhongping,Cao, Jianhua,Ge, Yonghui,Ma, Dongxu,Jiang, Guoqiang
p. 987 - 990
(2013/07/05)

INDUCTION OF ALPHA HELIX CONFORMATIONS IN PROTEINS AND PEPTIDES
Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.
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Page/Page column 14-15

(2012/07/14)

Asymmetric michael additions of α-nitrocyclohexanone to aryl nitroalkenes catalyzed by natural amino acid-derived bifunctional thioureas
A series of new thiourea catalysts prepared from natural amino acids have been applied in organocatalytic asymmetric Michael additions of α-nitrocyclohexanone to nitroalkenes. The resulting addition products are formed with excellent enantioselectivities (up to an er of 98:2) in good yields (up to 90%).
J?rres, Manuel,Schiffers, Ingo,Atodiresei, Iuliana,Bolm, Carsten
supporting information
p. 4518 - 4521
(2012/10/29)

Synthesis of optically active homotryptophan and its oxygen and sulfur analogues
d-Homotryptophan and its sulfur analogue have been synthesized by Sonogashira coupling between 3-iodoheteroarenes and ethynyloxazolidine followed by reduction of triple bond and oxidation of alcohol to acid. l-Homotryptophan and its oxygen analogue have b
Goswami, Koushik,Paul, Sibasish,Bugde, Sandesh T.,Sinha, Surajit
experimental part
p. 280 - 286
(2012/01/05)

Improved synthesis of rupintrivir
An improved synthesis of rupintrivir (AG7088) was accomplished using three amino acids (l-glutamic acid, d-4-fluorophenylalanine, and l-valine) as the building blocks. The key fragment ketomethylene dipeptide isostere was constructed with the valine derivative and phenylpropionic acid derivative, followed by coupling with a lactam derivative and an isoxazole acid chloride to provide AG7088 totally in eight steps.
Lin, Daizong,Qian, Wangke,Hilgenfeld, Rolf,Jiang, Hualiang,Chen, Kaixian,Liu, Hong
scheme or table
p. 1101 - 1107
(2012/09/08)

Total synthesis of argyrins A and e
The total synthesis of argyrins A and E were accomplished using a convergent strategy by condensation of one tripeptide and two dipeptide fragments. The synthesis strategy, which was developed for the protection of peptide fragments and identification of the optimum macrocylization site, can be applied to further synthetic studies involving other members of the argyrin family.
Wu, Wenbin,Li, Zheng,Zhou, Guangbiao,Jiang, Sheng
supporting information; experimental part
p. 2488 - 2491
(2011/05/09)

OPTICALLY ACTIVE -AMINO ACID INTO WHICH BSH IS INTRODUCED AND METHOD FOR SYNTHESIZING THE SAME
Disclosed is the method for producing an optically active BSH amino acid, which comprises a step of reacting an optically active α-amino acid derivative having a halogen in a side chain with a cyanoethyl BSH compound represented by formula (1). An optically active BSH amino acid obtained by the method is also disclosed.
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Page/Page column 8

(2011/05/14)

Total synthesis of (-)-indolactam v
The total synthesis of protein kinase C activator (-)-indolactam V (IL-V) has been successfully completed with two separate approaches: From known 4-nitrotryptophan derivative 3 in 8 steps (49% overall yield) and from l-glutamic acid in 12 steps (18% overall yield), where 4-nitrotryptophanol derivative 4 served as a key intermediate. Derivatives 3 and 4, both incorporating indole 4-substitution and the C-9 stereocenter in IL-V, were synthesized via the Pd-catalyzed indole synthesis from 3-nitro-2-iodoaniline 5 with aldehydes 6 and 7, respectively. Aldehyde 7 was, meanwhile, synthesized from l-glutamic acid in 5 steps (68% yield). Lactamization of the 9-membered ring was achieved using HATU in THF in good yield.
Xu, Zhengren,Zhang, Fengying,Zhang, Lihe,Jia, Yanxing
supporting information; experimental part
p. 2512 - 2517
(2011/05/06)

Total synthesis of chloptosin: A dimeric cyclohexapeptide
Here we describe in full our investigations into the synthesis of the dimeric cyclohexapeptide chloptosin in 17 linear steps. Particularly, this work features an organocatalytic tandem process for the synthesis of the embedded piperazic acids, in which a differentially protected azodicarboxylate is used together with pyrrolidinyl tetrazole as the catalyst. The central biaryl bond is being formed by Stille coupling of two sterically demanding ortho-chloropyrroloindole fragments. The inherent flexibility of the synthetic strategy proved beneficial as the route could be adjusted smoothly during the progression of the synthesis programme. Copyright
Oelke, Alexander J.,Antonietti, Francesca,Bertone, Leonardo,Cranwell, Philippa B.,France, David J.,Goss, Rebecca J. M.,Hofmann, Tatjana,Knauer, Stephan,Moss, Steven J.,Skelton, Paul C.,Turner, Richard M.,Wuitschik, Georg,Ley, Steven V.
scheme or table
p. 4183 - 4194
(2011/06/17)

STEREOSELECTIVE SYNTHESIS OF PIPERIDINE DERIVATIVES
This invention relates to dialdehyde or dinitrile compounds, which are useful for stereoselective synthesis of piperidine, pyrrolidine, and azepane derivatives.
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Page/Page column 9

(2010/06/22)

Synthetic aromatic amino acids from a negishi cross-coupling reaction
An N,O-protected, iodinated bishomoalanine derivative, safely available from glutamic acid, reacts with aryl halides in a Negishi reaction in high yields. From the coupling product, Fmoc-protected amino acids with aromatic and heteroaromatic side chains were generated in high yields by racemization-free procedures. These monomers could be used for solid-phase peptide synthesis. Georg Thieme Verlag Stuttgart.
Suhartono, Marcel,Schneider, Angelika E.,Duerner, Gerd,Goebel, Michael W.
experimental part
p. 293 - 303
(2010/03/30)

Synthetic studies on (-)-lemonomycin: An efficient asymmetric synthesis of lemonomycinone amide
Asymmetric synthesis of lemonomycinone amide (2) was accomplished from readily accessible starting materials. Enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester (11) by 5-tert- butyldimethylsilyloxy-2,4-dimethoxy-3-methylbenzyl bromide (10) in the presence of Corey-Lygo's phase transfer catalyst [O-(9)-ally-N-(9-anthracenylmethyl) cinchonidium bromide, 0.1 equiv] afforded, after chemoselective hydrolysis of the imine function (THF/H2O/AcOH), the substituted L-tert-butyl phenylalanate 13 in 85% yield. A Pictet-Spengler reaction of 14 with benzyloxyacetaldehyde (15) provided the 1,3-cisdisubstituted tetrahydroisoquinoline 16 in 85% yield as a single diastereomer. Coupling of hindered secondary amine 16 with amino acid 9 was accomplished under carefully controlled conditions to furnish the amide 22, which was in turn converted to hemiaminal 24. A hafnium triflate catalyzed conversion of hemiaminal to α-amino thioether followed by a silver tetrafluoroborate promoted intramolecular Mannich reaction of 26 afforded the tetracycle 27 in excellent overall yields. Debenzylation of 27 [Pd(OH)2, H2, MeOH, 0°C], removal of N-Boc function (aqueous 3 N HCl, MeOH/H2O), and oxidation of hydroquinone to quinone [(NH4)2Ce(NO 3)6, H2O, rt] afforded the lemonomycinone amide 2 in 76% yield over three steps
Wu, Yan-Chao,Bernadat, Guillaume,Masson, Geraldine,Couturier, Cedric,Schlama, Thierry,Zhu, Jieping
supporting information; experimental part
p. 2046 - 2052
(2009/08/07)

Thiyl glycosylate of olefinic proteins: S-linked glycoconjugate synthesis
Tagged for thiolation: A novel glycoconjugation strategy utilizes a non-natural olefin-containing amino acid (homoallylglycine, Hag) as a "tag" for modification and a photoinitiated hydroglycothiolation reaction that is selective only for the Hag olefinic "tag". Application of this method to a number of model proteins allowed complete and precise site-selective glycosylate generating glycoconjugates that include, for example, virus-like particles displaying up to 180 glycans at preselected positions (see scheme).
Floyd, Nicola,Vijayakrishnan, Balakumar,Koeppe, Julia R.,Davis, Benjamin G.
supporting information; experimental part
p. 7798 - 7802
(2010/04/05)

Efficient and selective cleavage of the t-butoxycarbonyl group from di-t-butylimidodicarbonate using catalytic bismuth(III) bromide in acetonitrile
Di-t-butylimidodicarbonates can be chemoselectively and efficiently deprotected to the corresponding mono-BOC-protected amines in high yields using a catalytic amount of bismuth(III) bromide in acetonitrile at room temperature. This method is mild and compatible with the presence of a wide range of functional and other protecting groups in the substrates, such as TBDMS, MOM and mono-BOC or Cbz-protected amines, etc. The method has advantages of ease of operation and use of nontoxic and inexpensive catalyst.
Zheng, Jianlong,Yin, Biaolin,Huang, Wenming,Li, Xiaopeng,Yao, Hequan,Liu, Zhaogui,Zhang, Jiancun,Jiang, Sheng
scheme or table
p. 5094 - 5097
(2009/12/01)

Preparation of a metal-ligand fluorescent chemosensor and enantioselective recognition of carboxylate anions in aqueous solution
Two chiral fluorescent chemosensors 1 and 2 were synthesized, and the structure characterized by IR, 1H NMR, 13C NMR, MS spectra and elemental analysis. Their recognition ability was studied in aqueous solution (Tris-HCl buffer pH 7.4, MeOH/H2O = 1:1) through fluorescence spectra. Receptors 1 and 2 showed a good binding ability to the copper ion. The host 1-Cu2+ complex showed a chiral recognition ability to mandelate anions with a preferable binding to l-mandelate than d-mandelate anions. The host 1-Cu2+ complex and l- or d-mandelate anions formed 1:1 stoichiometric complex. The binding constant for l-mandelate is 576 M-1, whereas that for d-mandelate is only 38 M-1, which can be distinguished by the different change of fluorescence intensity.
Chen, Zhi-hong,He, Yong-bing,Hu, Chen-Guang,Huang, Xiao-huan
p. 2051 - 2057
(2008/12/22)

Novel CADD-based peptidyl vinyl ester derivatives as potential proteasome inhibitors
A series of peptidyl vinyl ester derivatives bearing three different P1 substitutions as potential proteasome inhibitors were studied. The target molecules were designed based on CADD (computer aided drug design) protocol and synthesized. Their activities
Mou, Ke,Xu, Bo,Ma, Chao,Yang, Xiaoming,Zou, Xiaomin,Lue, Yang,Xu, Ping
p. 2198 - 2202
(2008/12/22)

Total synthesis of (-)-dysithiazolamide
(Chemical Equation Presented) The tetrachlorinated natural product (-)-dysithiazolamide was synthesized from L-glutamic acid in a convergent way, confirming the previously proposed (2S,4S,6S,8S) absolute stereochemistry.
Arda, Ana,Soengas, Raquel G.,Nieto, M. Isabel,Jimenez, Carlos,Rodriguez, Jaime
supporting information; experimental part
p. 2175 - 2178
(2009/05/26)

A practical method for selective cleavage of a tert-butoxycarbamoyl N-protective group from N,N-diprotected α-amino acid derivatives using montmorillonite K-10
A new, practical, and mild procedure for the selective cleavage of a tert-butoxycarbonyl group (Boc) in N-Boc-N-acyl-diprotected amines is described. When applied to α-amino acids, complete integrity of the stereochemistry was observed. The use of N,N-di-Boc-α-amino-δ- and γ-hydroxy esters provided both δ- and γ-lactones in very good yields. The method is based on the use of Montmorillonite K-10 either in CH 2Cl2 at room temperature or in toluene at 65°C and is compatible with the presence of a large range of functional and other protecting groups in the substrates. In most cases virtually pure samples are obtained after filtration and removal of solvents. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
Hernandez, J. Nicolas,Crisostomo, Fernando R. Pinacho,Martin, Tomas,Martin, Victor S.
p. 5050 - 5058
(2008/03/18)

Molecular iodine-catalyzed facile procedure for N-Boc protection of amines
An efficient and practical protocol for the protection of various structurally and electronically divergent aryl and aliphatic amines using (Boc)2O in the presence of a catalytic amount of molecular iodine (10 mol%) under solvent-free conditions at ambient temperature is presented.
Varala, Ravi,Nuvula, Sreelatha,Adapa, Srinivas R.
p. 8283 - 8286
(2007/10/03)

Synthesis, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor
A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, K i = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 μM) for SARS CoV and 5.2 log (at 1.25 μM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A?) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.
Yang, Syaulan,Chen, Shu-Jen,Hsu, Min-Feng,Wu, Jen-Dar,Tseng, Chien-Te K.,Liu, Yu-Fan,Chen, Hua-Chien,Kuo, Chun-Wei,Wu, Chi-Shen,Chang, Li-Wen,Chen, Wen-Chang,Liao, Shao-Ying,Chang, Teng-Yuan,Hung, Hsin-Hui,Shr, Hui-Lin,Liu, Cheng-Yuan,Huang, Yu-An,Chang, Ling-Yin,Hsu, Jen-Chi,Peters, Clarence J.,Wang, Andrew H.-J.,Hsu, Ming-Chu
p. 4971 - 4980
(2007/10/03)

A practical and efficient synthesis of thalidomide via Na/liquid NH 3 methodology
A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected L-glutamic acid diester via Na/ liquid (liq.) NH3 (-33°C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.
Varala, Ravi,Adapa, Srinivas R.
supporting information
p. 853 - 856
(2012/12/26)

Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitors
Design, synthesis, and biological evaluation of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease (SARS-3CLpro) inhibitors for severe acute respiratory syndrome coronavirus (SARS-CoV) are described. These inhibitors exhibited antiviral activity against SARS-CoV in infected cells in the micromolar range. An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors.
Ghosh, Arun K.,Xi, Kai,Ratia, Kiira,Santarsiero, Bernard D.,Fu, Wentao,Harcourt, Brian H.,Rota, Paul A.,Baker, Susan C.,Johnson, Michael E.,Mesecar, Andrew D.
p. 6767 - 6771
(2007/10/03)

Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters
The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide α,β-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 μM), the ketomethylene isosteres and tripeptide α,β-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 μM). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 μM is obtained by condensation of the Phe-Phe dipeptide α,β-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 μM.
Shie, Jiun-Jie,Fang, Jim-Min,Kuo, Tun-Hsun,Kuo, Chih-Jung,Liang, Po-Huang,Huang, Hung-Jyun,Wu, Yin-Ta,Jan, Jia-Tsrong,Cheng, Yih-Shyun E.,Wong, Chi-Huey
p. 5240 - 5252
(2007/10/03)

Protease inhibitors
This invention relates to treating an infection with a virus using protease inhibitors. Examples of the protease inhibitors include compounds of formula (I). Each variable is defined in the specification.
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Page/Page column 27

(2008/06/13)

COMBINATION THERAPY WITH INHIBITORS OF INDUCIBLE NITRIC OXIDE SYNTHASE AND ALKYLATING AGENTS
A combination therapy comprising administration of a carbamoylating chemotherapeutic agent in conjunction with administration of a selective iNOS inhibitor compound is disclosed. Optionally, resection and radiation therapy are provided with the therapeutic combination. A medicament comprising a carbamoylating chemotherapeutic agent and a selective iNOS inhibitor compound together with a pharmaceutically acceptable carrier is further disclosed. A kit comprising a carbamoylating chemotherapeutic agent and a selective iNOS inhibitor compound is further disclosed.
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Page/Page column 55-56; 100

(2010/02/11)

Protease inhibitors
This invention relates to treating an infection with a virus using protease inhibitors. Examples of the protease inhibitors include compounds of formula (II). Each variable is defined in the specification.
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(2008/06/13)