1201943-62-5Relevant articles and documents
Enantioselective synthesis of (1R,2S) and (1S,2S) dehydrocoronamic acids
Fliche,Braun,Le Goffic
, p. 2873 - 2876 (1994)
Thanks to the successive use of two esterases with different regioselectivities and conventional organic chemistry we have synthesized (1R,2S) and (1S,2S) dehydrocoronamic acids.
Epimerization reaction of a substituted vinylcyclopropane catalyzed by ruthenium carbenes: Mechanistic analysis
Zeng, Xingzhong,Wei, Xudong,Farina, Vittorio,Napolitano, Elio,Xu, Yibo,Zhang, Li,Haddad, Nizar,Yee, Nathan K.,Grinberg, Nelu,Shen, Sherry,Senanayake, Chris H.
, p. 8864 - 8875 (2006)
A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base
Kawashima, Aki,Shu, Shuangjie,Takeda, Ryosuke,Kawamura, Akie,Sato, Tatsunori,Moriwaki, Hiroki,Wang, Jiang,Izawa, Kunisuke,Acea, Jos Luis,Soloshonok, Vadim A.,Liu, Hong
, p. 973 - 986 (2016)
Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2′ alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.
Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA derivatives: Key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease
Beaulieu, Pierre L.,Gillard, James,Bailey, Murray D.,Boucher, Colette,Duceppe, Jean-Simon,Simoneau, Bruno,Wang, Xiao-Jun,Zhang, Li,Grozinger, Karl,Houpis, Ioannis,Farina, Vittorio,Heimroth, Heidi,Krueger, Thomas,Schnaubelt, Juergen
, p. 5869 - 5879 (2005)
(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.
A TEIXOBACTIN ANALOGUE AND USE THEREOF
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Paragraph 00183, (2021/01/29)
Provided herein belongs to the field of pharmaceuticals, and specifically relates to a Teixobactin analogue and use thereof. It further relates to a pharmaceutical composition comprising the compound and use of the compound and the pharmaceutical composit
Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by sequential SN2-SN2′ dialkylation of (R)-N-(benzyl)proline-derived glycine Schiff base Ni(ii) complex
Kawashima, Aki,Xie, Chen,Mei, Haibo,Takeda, Ryosuke,Kawamura, Akie,Sato, Tatsunori,Moriwaki, Hiroki,Izawa, Kunisuke,Han, Jianlin,Acea, Jos Luis,Soloshonok, Vadim A.
, p. 1051 - 1058 (2015/02/02)
This work describes a new process for the asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid of high pharmaceutical importance. The sequence of the reactions includes PTC alkylation (SN2), homogeneous SN2′ cyclization followed by disassembly of the resultant Ni(ii) complex. All reactions are conducted under operationally convenient conditions and suitably scaled up to 6 g of the starting Ni(ii) complex. This journal is
Synthesis of methyl-1-(tert -butoxycarbonylamino)-2- vinylcyclopropanecarboxylate via a hofmann rearrangement utilizing trichloroisocyanuric acid as an oxidant
Crane, Zackary D.,Nichols, Paul J.,Sammakia, Tarek,Stengel, Peter J.
supporting information; experimental part, p. 277 - 280 (2011/03/20)
A trichloroisocyanuric acid (TCCA) mediated Hofmann rearrangement was utilized to synthesize methyl-1-(tert-butoxycarbonylamino)-2- vinylcyclopropanecarboxylate. A variety of functional groups are tolerated in this reaction including vinyl, cyclopropyl, pyridyl, aryl, benzyl, and nitro groups.
Inhibitors of Serine Proteases
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, (2010/12/26)
The present invention relates to compounds that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.
INHIBITORS OF SERINE PROTEASES FOR THE TREATMENT OF HCV INFECTIONS
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Page/Page column 467-468, (2008/12/07)
The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof. These compounds inhibit serine protease, particularly the hepatitis C virus NS3-NS4A protease.
MACROCYCLIC HEPATITIS C PROTEASE INHIBITORS
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Page/Page column 50-51, (2008/12/07)
The present invention provides novel macrocyclic compounds that mimic peptide substrates of the hepatitis C viral protease and inhibit the viral protease, more particularly as inhibitors of the NS3 serine protease from hepatitis C virus. Methods for synthesis of the compounds are also provided. The compounds find utility as antiviral agents directed at hepatitis C. The invention further provides methods of employing such inhibitors, alone or in combination with other therapeutic agents, to treat hepatitis C infection in a subject in need of such treatment.
