40638-98-0Relevant academic research and scientific papers
Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
, p. 557 - 565 (2013/03/13)
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
Production of (R)-3-amino-3-phenylpropionic acid and (S)-3-amino-3- phenylpropionic acid from (R,S)-N-acetyl-3-amino-3-phenylpropionic acid using microorganisms having enantiomer-specific amidohydrolyzing activity
Kawasaki, Hisashi,Koyama, Koutaro,Kurokawa, Sachio,Watanabe, Kunihiko,Nakazawa, Masakazu,Izawa, Kunisuke,Nakamatsu, Tsuyoshi
, p. 99 - 106 (2008/02/08)
(R)-3-Amino-3-phenylpropionic acid ((R)-β-Phe) and (S)-3-amino-3-phenylpropionic acid ((S)-β-Phe) are key compounds on account of their use as intermediates in synthesizing pharmaceuticals. Enantiomerically pure non-natural amino acids are generally prepared by enzymatic resolution of the racemic N-acetyl form, but despite the intense efforts this method could not be used for preparing enantiomerically pure β-Phe, because the effective enzyme had not been found. Therefore, screening for microorganisms capable of amidohydrolyzing (R,S)-N-acetyl-3-amino-3-phenylpropionic acid ((R,S)-N-Ac-β-Phe) in an enantiomer-specific manner was performed. A microorganism having (R)-enantiomer-specific amidohydrolyzing activity and another having both (R)-enantiomer- and (S)-enantiomer-specific amidohydrolyzing activities were obtained from soil samples. Using 16S rDNA analysis, the former organism was identified as Variovorax sp., and the latter as Burkholderia sp. Using these organisms, enantiomerically pure (R)-β-Phe (> 99.5% ee) and (S)-β-Phe (> 99.5% ee) with a high molar conversion yield (67%-96%) were obtained from the racemic substrate.
PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE BETA-PHENYLALANINE DERIVATIVES
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Page 8, (2008/06/13)
The present application discloses a method for the production of an optically active β-phenylalanine derivative in which an N-acyl-β-phenylalanine derivative is made to react with a specific optically resolving agent to conduct an optical resolution by fo
Synthesis of small cyclic peptides via intramolecular Heck reactions
Reddy, P. Rajamohan,Balraju,Madhavan,Banerji, Biswadip,Iqbal, Javed
, p. 353 - 356 (2007/10/03)
Tripeptides having a 3-bromobenzyl group at the C-termini and an acryloyl group at the N termini undergo efficient intramolecular Heck reactions to afford the corresponding cyclic peptides in good yields. Synthesis of two such peptides is discussed.
Synthesis of a cyclic pseudo 310 helical structure from a β-amino acid-L-proline derived tripeptide via a ring closing metathesis reaction
Banerji, Biswadip,Mallesham,Kiran Kumar,Kunwar,Iqbal, Javed
, p. 6479 - 6483 (2007/10/03)
The combination of homo-phenylglycine (Hpg) and proline leads to the formation of a β-turn mimic, which can be transformed into a cyclic peptide using a ring closing metathesis reaction. The presence of the pentenoyl and allyl groups at the terminus of th
β-substituted β-phenylpropionyl chymotrypsins. Structural and stereochemical features in stable acyl enzymes
Reed,Katzenellenbogen
, p. 1162 - 1176 (2007/10/02)
In order to develop effective alternate substrate inhibitors for serine proteases, we have prepared a series of β-substituted β-phenylpropionic acid esters related to some systems known to form stable acyl enzymes with α-chymotrypsin. Some of these compounds were prepared in enantiomerically pure form by asymmetric synthesis. Acyl enzyme species were generated from chymotrypsin by reaction with the active esters, and the progress of deacylation was monitored by the proflavin displacement assay. In some cases, it was possible to distinguish two different deacylation rates that correspond to the two enantiomers. β-Phenylpropionic acyl enzymes with β-substituents that are nonpolar were not especially stable, but a number of the polar derivatives and particularly the acylamino derivatives showed slow rates of deacylation (k(d) less than 0.005 min-1), with three systems showing deacylation enantioselectivities in the range of 500-1500. These results are consistent with a model in which additional stabilization of the acyl enzyme and enantioselectivity in the deacylation process derives from an additional hydrogen bond between the acyl enzyme species (as an acceptor) and the enzyme (as a donor). A number of active site residues that might be involved in this hydrogen bond are discussed.
