Chemoenzymatic approach to optically active phenylglycidates: resolution of bromo- and iodohydrins
Chemoenzymatic approach to optically active phenylglycidates: resolution of bromo- and iodohydrins
复制标题
DOI：
10.1016/j.tetasy.2004.08.026
复制
发表时间：
2004-10-04
影响因子：
--
通讯作者：
Qazi, GN
中科院分区：
文献类型：
--
作者：
Anand, N;Kapoor, M;Qazi, GN
对映体富集的苯基缩水甘油酸酯，紫杉醇C-13苯基异丝氨酸侧链和地尔硫卓的前体。通过动力学拆分反式-2-溴-3-羟基-和反式-3-羟基-2-碘苯基丙酸酯来制备，以提供对映体化的（2 R，3R）-和（2S，3S）-卤代醇。卤代醇中溴代和碘代基团的庞大性和易变性使得它们难以接近用于水解其酰氧基衍生物的大多数脂肪酶的活性位点。在本文筛选的一组22种水解酶中，包括天然酶以及商业酶，只有尼日尔曲霉（脂肪酶AS，AMANO）可以以高对映选择性（E = 176）催化水解。拆分的卤代醇容易转化为相应的（2S，3R）-和（2 R，3S）苯基缩水甘油酸酯。(C)26 E 'lsevier Ltd.保留所有权利。
Enantiomerically enriched phenylglycidates, precursors of the taxol C-13 phenylisoserine side chain and diltiazem. were prepared by kinetic resolution of anti-2-bromo-3-hydroxy- and anti-3-hydroxy-2-iodophenylpropanoates to provide enantioriched (2R,3R)- and (2S,3S)-halohydrins. The bulkiness and inflexibility of bromo and iodo groups in halohydrins have made them inaccessible to the active site of most of the lipases utilized for the hydrolysis of their acyloxy derivatives. In a set of 22 hydrolases screened herein, including native as well as commercial enzymes, only Aspergillus niger (Lipase AS, AMANO) could catalyze the hydrolysis with high enantioselectivity (E = 176). The resolved halohydrins easily underwent transformation to the corresponding (2S,3R)- and (2R,3S)phenylglycidates. (C) 26 E'lsevier Ltd. All rights reserved.