通过 CALB 催化水解制备对映体 5-8 元碳环β-氨基酸衍生物的绿色策略。

Green Strategies for the Preparation of Enantiomeric 5-8-Membered Carbocyclic β-Amino Acid Derivatives through CALB-Catalyzed Hydrolysis.

机构信息

Institute of Pharmaceutical Chemistry, Interdisciplinary Excellence Center, Faculty of Pharmacy, University of Szeged, H-6720 Szeged, Hungary.

MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, H-6720 Szeged, Hungary.

出版信息

Molecules. 2022 Apr 18;27(8):2600. doi: 10.3390/molecules27082600.

DOI:10.3390/molecules27082600

PMID:35458798

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9032184/

Abstract

Candida antarctica lipase B-catalyzed hydrolysis of carbocyclic 5−8-membered cis β-amino esters was carried out in green organic media, under solvent-free and ball-milling conditions. In accordance with the high enantioselectivity factor (E > 200) observed in organic media, the preparative-scale resolutions of β-amino esters were performed in tBuOMe at 65 °C. The unreacted β-amino ester enantiomers (1R,2S) and product β-amino acid enantiomers (1S,2R) were obtained with modest to excellent enantiomeric excess (ee) values (ees > 62% and eep > 96%) and in good chemical yields (>25%) in one or two steps. The enantiomers were easily separated by organic solvent/H2O extraction.

摘要

在绿色有机溶剂中，无溶剂和球磨条件下，南极假丝酵母脂肪酶 B 催化的碳环 5-8 元顺式β-氨基酯的水解。根据在有机溶剂中观察到的高对映选择性因子（E > 200），在 tBuOMe 中于 65°C 进行了β-氨基酯的制备规模拆分。未反应的β-氨基酯对映异构体（1R,2S）和产物β-氨基酸对映异构体（1S,2R）以中等至优异的对映体过量（ee）值（ee > 62% 和 eep > 96%）和良好的化学收率（>25%）在一步或两步中获得。通过有机溶剂/H2O 萃取可以轻松分离对映异构体。