105560-93-8Relevant articles and documents
Lipase activity of Lecitase Ultra: characterization and applications in enantioselective reactions
Mishra, Mithilesh Kumar,Kumaraguru, Thenkrishnan,Sheelu, Gurrala,Fadnavis, Nitin W.
, p. 2854 - 2860 (2009)
The general properties of Lecitase Ultra, a phospholipase manufactured and marketed by Novozymes, Denmark, have been studied after purification by ultrafiltration. The enzyme has a molecular mass of 35 KD, pH-optimum of 8.5, and appears to possess a single active site which exhibits both the lipase and phospholipase activities that increase in the presence of Ca2+ and Mg2+ ions. The enzyme is inhibited by heavy metal ions and surfactants, and does not accept p-nitrophenyl acetate and glycerol triacetate. Substrates, such as glycerol tributyrate and p-nitrophenyl palmitate, esters of N-acetyl-α-amino acids and α-hydroxy acids are readily accepted. Amino acids with aliphatic residues, such as alanine, isoleucine, and methionine, are hydrolyzed with high enantioselectivity for the l-enantiomer (E >100), but amino acids with aromatic residues such as phenylalanine and phenylglycine, and esters of α-hydroxy acids are hydrolyzed with low enantioselectivity (E = 1-5). Immobilization of the enzyme in a gelatin matrix (gelozyme) leads to a marginal improvement in the enantioselectivity for these substrates. However, a dramatic improvement in enantioselectivity is observed for ethyl 2-hydroxy-4-oxo-4-phenylbutyrate (E value increases from 4.5 to 19.5 with S-selectivity). Similarly, glycidate esters, such as ethyl trans-(±)-3-phenyl glycidate and methyl trans-(±)-3-(4-methoxyphenyl) glycidate, are selectively hydrolyzed with a remarkable selectivity towards the (2S,3R)-enantiomer providing unreacted (2R,3S)-glycidate esters (ee >99%, conversion 52-55%) by the immobilized enzyme.
Asymmetric synthesis of methyl (2R,3S)-3-(4-methoxyphenyl) glycidate, a key intermediate of diltiazem, via Mukaiyama aldol reaction
Imashiro, Ritsuo,Kuroda, Tooru
, p. 1313 - 1315 (2001)
Methyl (2R,3S)-3-(4-methoxyphenyl) glycidate, a key intermediate of diltiazem, was synthesized in good yield with high enantioselectivity based on chiral oxazaborolidine-mediated Mukaiyama aldol reaction of p-anisaldehyde with α,α-dichloro silyl ketene acetal (up to 96% ee), followed by reduction and cyclization.
Asymmetric reduction of aromatic ketones. II. An enantioselective synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate
Matsuki,Sobukawa,Kawai,Inoue,Takeda
, p. 643 - 648 (1993)
Asymmetric reduction of some 3-keto esters (6, 8, and 11) to 3-hydroxy esters (7, 9, and 12) with various chiral reducing agents was investigated. The products (9 and 12) were converted to methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (2R,3S-3), a key intermediate in the practical enantioselective synthesis of diltiazem (1).
Bioresolution production of (2R,3S)-Ethyl-3-phenylglycidate for chemoenzymatic synthesis of the taxol C-13 side chain by galactomyces geotrichum ZJUTZQ200, a new epoxide-hydrolase-producing strain
Wei, Chun,Ling, Jinlong,Shen, Honglei,Zhu, Qing
, p. 8067 - 8079 (2014/07/08)
A newly isolated Galactomyces geotrichum ZJUTZQ200 strain containing an epoxide hydrolase was used to resolve racemic ethyl 3-phenylglycidate (rac-EPG) for producing (2R,3S)-ethyl-3-phenylglycidate ((2R,3S)-EPG). G. geotrichum ZJUTZQ200 was verified to be able to afford high enantioselectivity in whole cell catalyzed synthesis of this chiral phenylglycidate synthon. After the optimization of the enzymatic production and bioresolution conditions, (2R,3S)-EPG was afforded with high enantioselectivity (e.e.S > 99%, E > 49) after a 8 h reaction. The co-solvents, pH buffer solutions and substrate/cell ratio were found to have significant influences on the bioresolution properties of G. geotrichum ZJUTZQ200. Based on the bioresolution product (2R,3S)-EPG, taxol's side chain ethyl (2R,3S)-3-benzoylamino-2-hydroxy- 3-phenylpropionate was successfully synthesized by a chemoenzymatic route with high enantioselectivity (e.e.S > 95%).
An unusual (R)-selective epoxide hydrolase with high activity for facile preparation of enantiopure glycidyl ethers
Zhao, Jing,Chu, Yan-Yan,Li, Ai-Tao,Ju, Xin,Kong, Xu-Dong,Pan, Jiang,Tang, Yun,Xu, Jian-He
experimental part, p. 1510 - 1518 (2011/08/03)
A novel epoxide hydrolase (BMEH) with unusual (R)-enantioselectivity and very high activity was cloned from Bacillus megaterium ECU1001. Highest enantioselectivities (E>200) were achieved in the bioresolution of ortho-substituted phenyl glycidyl ethers and para-nitrostyrene oxide. Worthy of note is that the substrate structure remarkably affected the enantioselectivities of the enzyme, as a reversed (S)-enantiopreference was unexpectedly observed for the ortho-nitrophenyl glycidyl ether. As a proof-of-concept, five enantiopure epoxides (>99% ee) were obtained in high yields, and a gram-scale preparation of (S)-ortho-methylphenyl glycidyl ether was then successfully performed within a few hours, indicating that BMEH is an attractive biocatalyst for the efficient preparation of optically active epoxides. Copyright
