Highly efficient resolution of N-hydroxymethyl vince lactam by solvent stable lipase YCJ01

Q2 Chemical Engineering Journal of Molecular Catalysis B-enzymatic Pub Date : 2016-11-01 DOI:10.1016/j.molcatb.2016.12.009

Ling Zhu , Fucheng Zhu , Song Qin , Bin Wu , Bingfang He

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引用次数: 4

Abstract

Both optically pure enantiomers of N-hydroxymethyl vince lactam are the key synthons for some important antiviral drugs. The high enantioselective transesterification of N-hydroxymethyl vince lactam was catalyzed by the lipase from Burkholderia ambifaria YCJ01 using vinyl acetate as the acyl donor. Under the optimized conditions, an efficient resolution of N-hydroxymethyl vince lactam in high substrate concentration (300 mM; 41.7 g/L) was obtained with nearly theoretical conversion yield of 50.1%, ee_p of 99% and ee_s of 99%. Strikingly, the highest enantioselectivity (E > 900) and dramatic increase of the lipase activity towards N-hydroxymethyl vince lactam were observed in a binary solvent system with hexane and MTBE (v/v = 1:9). The high substrate tolerance and enantioselectivity of lipase YCJ01 showed significant benefit in the practical resolution of racemic N-hydroxymethyl vince lactam. Additionally, the high enantiopreference of lipase YCJ01 towards (−)-N-hydroxymethyl vince lactam was also rationalized through molecular docking.

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溶剂稳定型脂肪酶YCJ01高效分解n -羟甲基vince内酰胺

n -羟甲基文斯内酰胺的两种光学纯对映体都是一些重要抗病毒药物的关键合成子。以醋酸乙烯酯为酰基供体，利用两歧伯克霍尔德菌YCJ01脂肪酶催化n -羟甲基vince内酰胺的高对映选择性酯交换反应。在优化条件下，n -羟甲基vince内酰胺在高底物浓度(300 mM;41.7 g/L)，接近理论转化率为50.1%，ep为99%，ees为99%。引人注目的是，最高的对映体选择性(E >在正己烷和MTBE (v/v = 1:9)二元溶剂体系中，脂肪酶对n -羟甲基vince内酰胺的活性显著增加。脂肪酶YCJ01的高底物耐受性和对映体选择性对外消旋n -羟甲基vince内酰胺的实际拆分有显著的好处。此外，脂肪酶YCJ01对(−)- n -羟甲基vince内酰胺的高对映性也通过分子对接得到了合理化。

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来源期刊

Journal of Molecular Catalysis B-enzymatic 生物-生化与分子生物学

CiteScore

2.58

自引率

0.00%

发文量

审稿时长

3.4 months

期刊介绍： Journal of Molecular Catalysis B: Enzymatic is an international forum for researchers and product developers in the applications of whole-cell and cell-free enzymes as catalysts in organic synthesis. Emphasis is on mechanistic and synthetic aspects of the biocatalytic transformation. Papers should report novel and significant advances in one or more of the following topics; Applied and fundamental studies of enzymes used for biocatalysis; Industrial applications of enzymatic processes, e.g. in fine chemical synthesis; Chemo-, regio- and enantioselective transformations; Screening for biocatalysts; Integration of biocatalytic and chemical steps in organic syntheses; Novel biocatalysts, e.g. enzymes from extremophiles and catalytic antibodies; Enzyme immobilization and stabilization, particularly in non-conventional media; Bioprocess engineering aspects, e.g. membrane bioreactors; Improvement of catalytic performance of enzymes, e.g. by protein engineering or chemical modification; Structural studies, including computer simulation, relating to substrate specificity and reaction selectivity; Biomimetic studies related to enzymatic transformations.