109721-08-6Relevant articles and documents
Engineering of the Conformational Dynamics of Lipase to Increase Enantioselectivity
Yang, Bin,Wang, Hongjiang,Song, Wei,Chen, Xiulai,Liu, Jia,Luo, Qiuling,Liu, Liming
, p. 7593 - 7599 (2017)
In order to increase the R-enantioselectivity of Candida antarctica lipase B (CALB) toward (R)-3-t-butyl-dimethyl-silyloxy glutaric acid methyl monoester at 30 °C, we engineered CALB conformational dynamics. Based on structural analysis and molecular dynamics simulations, two key residues (D223 and A281) were identified, and three mutants (D223V, A281S, and D223V/A281S) were designed to decrease the conformational dynamics of the pocket and channel. Computational and experimental evaluations were performed for all mutants, with the D223V/A281S mutant exhibiting high R-enantioselectivity (>99.00%; increased from 8.00%) and high space-time yield (107.54 g L-1 d-1 a 5.70-fold increase).
Green synthesis of (R)-3-TBDMSO glutaric acid methyl monoester using Novozym 435 in non-aqueous media
Wang, Hongjiang,Li, Zebiao,Yu, Xiaoxia,Chen, Ruidong,Chen, Xiulai,Liu, Liming
, p. 75160 - 75166 (2015)
An efficient biocatalytic synthesis of (R)-3-TBDMSO glutaric acid methyl monoester (R-J6), an important intermediate in the synthesis of rosuvastatin, has been developed using a green catalytic route in the presence of lipase, conducted under mild conditions without additional chiral reagents. Enzyme screening indicated Novozym 435 to be the most efficient biocatalyst for R-J6 synthesis. Methanol, which was the most effective alcohol for synthesis of R-monoester, was identified as the best acyl acceptor by molecular docking. The optimal conditions for synthesis of R-J6 were as follows: 50 g L-1 catalyst, 3 sp;:sp;1 molar ratio of methanol sp;:sp;substrate, 200 g L-1 substrate, iso-octane as solvent, orbital shaking at 200 rpm, and an incubation time of 24 h at 35°C. The key factor affecting the yield of R-J6 was the molar ratio of methanol to substrate found by an orthogonal array experimental design. Consequently, the desired product, R-J6, was afforded with a titer of 117.2 g L-1, a yield of 58.6%, and productivity of 4.88 g L-1 h-1. This green method holds promise for the preparation of kilogram quantities of (R)-3-substituted glutaric acid monoesters.
Synthesis of Novel HMG-CoA Reductase Inhibitors, I Naphthalene Analogs of Mevinolin
Novak, Lajos,Rohaly, Janos,Poppe, Laszlo,Hornyanszky, Gabor,Kolonits, Pal,et al.
, p. 145 - 158 (2007/10/02)
The title compounds 2 and their corresponding (6S) epimers 18 are prepared in several steps by starting with chiral formyl ester 5, and α-tetralones 10: (1) coupling reaction with the ylide generated from 11 to yield unsaturated ester 13, (2) reduction to the corresponding alcohol 14, (3) addition of the Grignard reagent derived from 14 to formyl ester 5 to afford the hydroxy esters 16 and 17, and (4) lactonization.This procedure is also used to synthesize the β-naphthyl analogs 29 and 30.Some results obtained from HMG-CoA reductase inhibitor screening are also reported. Key Words: HMG-CoA reductase inhibitors / Naphthylacetates / Pig liver esterase / Glutarate, 3-hydroxy / Lactones
