- An improved protocol for the preparation of (S)-vinylglycine from (S)-methionine
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We present an optimized procedure for the synthesis of (S)-vinylglycine from (S)-methionine. The key step is a solvent free pyrolysis of an intermediate sulfoxide at high temperature. Using our optimized reaction conditions, Cbz-protected vinylglycine was
- Kuechenthal,Migenda, Julia,Polednia, Magdalena,Maison, Wolfgang
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Read Online
- Electrophilic Chlorine from Chlorosulfonium Salts: A Highly Chemoselective Reduction of Sulfoxides
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Herein, we describe a selective late-stage deoxygenation of sulfoxides based on a novel application of chlorosulfonium salts and demonstrate a new process using these species generated in situ from sulfoxides as the source of electrophilic chlorine. The use of highly nucleophilic 1,3,5-trimethoxybenzene (TMB) as the reducing agent is described for the first time and applied in the deoxygenation of simple and functionalized sulfoxides. The method is easy to handle, economic, suitable for gram-scale operations, and readily applied for poly-functionalized molecules, as demonstrated with more than 45 examples, including commercial medicines and analogues. We also report the results of competition experiments that define the more reactive sulfoxide and we present a mechanistic proposal based on substrate and product observations.
- Acosta-Guzmán, Paola,Mahecha-Mahecha, Camilo,Gamba-Sánchez, Diego
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supporting information
p. 10348 - 10354
(2020/07/13)
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- An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds
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Herein, we describe the development of a simple, high yielding and stereocontrolled strategy for the synthesis of a series of triazolopiperazines and other biologically relevant fused scaffolds from optically active amino acids. This route was applied to the synthesis of 22 scaffolds containing new, previously inaccessible vectors and used to access a novel analogue of ganaplacide.
- Bond, Andrew D.,Hanby, Abigail R.,King, Thomas A.,Moss, Thomas A.,Sore, Hannah F.,Spring, David R.,Stewart, Hannah L.
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supporting information
p. 6818 - 6821
(2020/07/04)
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- C(sp3)?H Cyanation Promoted by Visible-Light Photoredox/Phosphate Hybrid Catalysis
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Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a C(sp3)?H cyanation reaction promoted by visible-light photoredox/phosphate hybrid catalysis was developed. Phosphate radicals, generated by one-electron photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst to produce nucleophilic carbon radicals from C(sp3)?H bonds with a high bond-dissociation energy. The resulting carbon radicals were trapped by a cyano radical source (TsCN) to produce the C?H cyanation products. Due to the high functional-group tolerance and versatility of the cyano group, the reaction will be useful for realizing streamlined building block syntheses and late-stage functionalization of drug-like molecules.
- Wakaki, Takayuki,Sakai, Kentaro,Enomoto, Takafumi,Kondo, Mio,Masaoka, Shigeyuki,Oisaki, Kounosuke,Kanai, Motomu
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supporting information
p. 8051 - 8055
(2018/06/15)
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- Amidation of unactivated ester derivatives mediated by trifluoroethanol
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A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity.
- McPherson, Christopher G.,Caldwell, Nicola,Jamieson, Craig,Simpson, Iain,Watson, Allan J. B.
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supporting information
p. 3507 - 3518
(2017/04/26)
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- Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
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An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright
- You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
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p. 557 - 565
(2013/03/13)
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- Macrocyclic Cysteine Protease Inhibitors and Compositions Thereof
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The present invention provides a novel class of macrocyclic compounds, which are useful as cysteine protease inhibitors. Also provided are novel intermediates and methods of preparing the compounds. The invention also provides pharmaceutical compositions
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- An efficient and scalable synthesis of N-(benzyloxycarbonyl)- and N-(methyloxycarbonyl)-(S)-vinylglycinol
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An efficient and scalable synthesis of N-(benzyloxycarbonyl)- and N-(methyloxycarbonyl)-(S)-vinylglycinol has been reported starting from the commercially available (l)-methionine. The scale-up preparation consisted of 5 steps and delivered up to 50 g of the desired N-protected β-amino alcohols in 32% and 36% overall yields.
- Lumbroso, Alexandre,Coeffard, Vincent,Le Grognec, Erwan,Beaudet, Isabelle,Quintard, Jean-Paul
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supporting information; experimental part
p. 3226 - 3228
(2010/08/19)
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- Straightforward synthesis of chiral silylated amino acids through hydrosilylation
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A method using hydrosilylation of unsaturated amino acids was developed and optimised to obtain silylated amino acids. The platinum (Bu4N) 2PtCl6 complex was identified as the best catalyst, and the procedure tolerated dif
- Marchand, Damien,Martinez, Jean,Cavelier, Florine
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experimental part
p. 3107 - 3112
(2009/05/11)
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- Resolution of non-protein amino acids via Carica papaya lipase-catalyzed enantioselective transesterification
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Carica papaya lipase-catalyzed transesterification of the 2,2,2-trifluoroethyl esters of N-benzyloxycarbonylated dl-amino acids carrying aliphatic side chains proceeded smoothly and, in almost all the cases, enantiospecifically (E = >200), affording the l-methyl esters and leaving the d-trifluoroethyl esters intact.
- Miyazawa, Toshifumi,Onishi, Kazuki,Murashima, Takashi,Yamada, Takashi,Tsai, Shau-Wei
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p. 2569 - 2573
(2007/10/03)
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- Enantioselective Synthesis of Non-Natural Aromatic α-Amino Acids
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We present two complementary methods for the stereoselective synthesis of non-natural α-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the α-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.
- Krebs, Andreas,Ludwig, Verena,Pfizer, Jose,Duerner, Gerd,Goebel, Michael W.
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p. 544 - 553
(2007/10/03)
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- Synthesis of new 3- and 4-substituted analogues of acyl homoserine lactone quorum sensing autoinducers
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The quorum sensing mechanism in Gram-negative bacteria uses small intercellular signal molecules, N-acyl-homoserine lactones (AHLs), to control transcription of specific genes in relation to population density. In this communication, we describe the parallel synthesis of new AHL analogues, in which substituents have been introduced into the 3- and 4-positions of the lactone ring. These analogues have been screened for their ability to activate and inhibit a Vibrio fischeri LuxI/LuxR-derived quorum sensing reporter system.
- Olsen,Severinsen,Rasmussen,Hentzer,Givskov,Nielsen
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p. 325 - 328
(2007/10/03)
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- Cleavage of benzyloxycarbonyl-5-oxazolidinones to α-benzyloxycarbonylamino-α-alkyl esters by alcohols and sodium hydrogen carbonate
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The reaction of benzyloxycarbonyl-5-oxazolidinones with alcohols and sodium hydrogen carbonate to afford the corresponding benzyloxycarbonyl esters is described.
- Allevi, Pietro,Cighetti, Giuliana,Anastasia, Mario
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p. 5319 - 5321
(2007/10/03)
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- Efficient reduction of sulfoxides with 2,6-dihydroxypyridine
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2,6-Dihydroxypyridine was found to be an efficient reagent in the deoxygenation of sulfoxides. The mild reaction conditions were compatible with functional groups such as ester and carbamate. It was also found that approximately 0.25 equivalents of 2,6-dihydroxypyridine was required for effective reduction. (C) 2000 Elsevier Science Ltd.
- Miller, Samantha J.,Collier, Talia R.,Wu, Weiming
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p. 3781 - 3783
(2007/10/03)
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- Asymmetric Synthesis of Both Enantiomers of Vigabatrin: An Approach Using Methionine as the Chiral Pool
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Both enantiomers of the potent GABA-T inhibitor, 4-amino-5-hexenoic acid (2), were prepared in five steps from (R)- or (S)-methionine using a one-pot reduction-homologation of an α-amino ester as the key reaction step.
- Wei, Zhong-Yong,Knaus, Edward E.
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p. 5569 - 5578
(2007/10/02)
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- Syntheses and Reactions of Silyl Carbamates. 1. Chemoselective Transformation of Amino Protecting Groups via tert-Butyldimethylsilyl Carbamates
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The N-tert-butyldimethylsilyloxycarbonyl group (silyl carbamate) was synthesized from commonly used amino protecting groups such as N-tert-butoxycarbonyl (Boc) and N-benzyloxycarbonyl (Z) by treatment with tert-butyldimethylsilyl trifluoromethanesulfonate/2,6-lutidine and tert-butyldimethylsilane/Pd(OAc)2, respectively.This novel species, upon activation with fluoride ion, reacts with a variety of electrophiles to give N-ester type compounds in high yield.For example, the conversion of N-t-Boc compounds into their corresponding N-Z compounds via a silyl carbamate was accomplished under these mild reaction conditions.
- Sakaitani, Masahiro,Ohfune, Yasufumi
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p. 870 - 876
(2007/10/02)
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- Tertiary-butyldimethylsilyl carbamate derivative and process for producing the same
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A t-butyldimethylsilyl carbamate derivative and a process for producing the same are disclosed. Tertiary-butyldimethylsilyl carbamate derivatives having the following general formula (1) are intermediates for the production of a variety of carbamate ester
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- N-(BENZYLOXYCARBONYL)-L-VINYLGLYCINE METHYL ESTER FROM L-METHIONINE METHYL ESTER HYDROCHLORIDE
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A reproducible, large scale and practical synthesis of N-(benzyloxycarbonyl)-L-vinylglycine methyl ester starting from L-methionine methyl ester hydrochloride is described.
- Meffre, Patrick,Vo-Quang, Liliane,Vo-Quang, Yen,Goffic, Francois Le
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p. 3457 - 3468
(2007/10/02)
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- SELECTIVE TRANSFORMATION OF N-t-BUTOXYCARBONYL GROUP INTO N-ALKOXYCARBONYL GROUP via N-CARBOXYLATE ION EQUIVALENT
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Reaction of a variety of N-t-butoxycarbonyl compounds with t-butyldimethylsilyl trifluoromethanesulfonate afforded the N-t-butyldimethylsilyloxycarbonyl compounds, chemoselectively, which upon treatment with an alkyl or aryl halide provided the corresponding N-alkoxy- or N-aryloxycarbonyl compounds, efficiently.
- Sakaitani, Masahiro,Ohfune, Yasufumi
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p. 5543 - 5546
(2007/10/02)
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- L-Vinylglycine
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Optically pure L-vinylglycine (1) has been synthesized from L-methionine in 54percent overall yield.The process consists in first preparing N-methionine methyl ester (9) which is then oxidized to methyl 2-amino>-
- Afzali-Ardakani, Ali,Rapoport, Henry
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p. 4817 - 4820
(2007/10/02)
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