Enzyme-Mediated Enantioselective Hydrolysis of Aliphatic Dicarboxylic Acid Diesters

Yuta Igawa,Kazutsugu Matsumoto,Hironobu Ise,Sakina Ichinoseki,Ai Kobayashi,Fumie Maeda

doi:10.4236/jbnb.2017.81004

Abstract

The enzyme-mediated highly enantioselective hydrolysis of aliphatic dicarboxylic acid diesters has been developed. The racemic diesters were easily prepared by the coupling of racemic alcohols with dicarboxylic anhydrides followed by esterification or with dicarboxylic acids. In the cases of bis(1-phenylethyl) glutarate and bis(1-phenylethyl) adipate, the diesters which contained the dl- and meso-form diastereomers, were enantioselectively hydrolyzed by lipase from Candida antarctica (Novozym 435) in buffer at 30°C to afford the almost optically pure (R)-1-phenylethanol. On the other hand, the following chemical hydrolysis of the remaining (S, S)-diesters and (S)-monoesters gave the (S)-alcohol. Finally, both enantiomers were stoichiometrically obtained in about 100% isolated yield based on the racemic diesters. The enzymatic reaction was also applicable for the preparation of several optically active alcohols. In some cases, both the reactivities and enantioselectivities were quite different from those in the case of the corresponding simple acetates.

Highlights

The enzyme-mediated kinetic resolution of racemic alcohols and esters is one of the attractive methods for the preparation of optically active compounds [1] [2] [3] [4]
The racemic diesters were prepared by the coupling of racemic alcohols with dicarboxylic anhydrides followed by esterification or with dicarboxylic acids
We succeeded in the enantioselective hydrolysis of poly(ethylene glycol) (PEG; av MW 4600)-supported carbonates (1) using porcine pancreas lipase (PPL; Scheme 1) [5]

Summary

Introduction

The enzyme-mediated kinetic resolution of racemic alcohols and esters is one of the attractive methods for the preparation of optically active compounds [1] [2] [3] [4]. We succeeded in the enantioselective hydrolysis of poly(ethylene glycol) (PEG; av MW 4600)-supported carbonates (1) using porcine pancreas lipase (PPL; Scheme 1) [5]. In this case, two molecules of the optically active 1-phenylethanol (2) could be released from one molecule of the substrate 1, and the theoretical total yield of 2 was up to 200%. The reactivity and enantioselectivitiy were moderate, and the amount of alcohols immobilized per gram of 1 (the loading capacity) was very low This drawback is a limiting step for the preparative synthesis of the desirable enantiomer.

Methods

Results

Conclusion