Development of a Practical Mass Spectrometry Based Assay for Determining Enantiomeric Excess. A fast and Convenient Method for the Optimization of PLE-Catalyzed Hydrolysis of Prochiral Disubstituted Malonates

Document Type

Article

Publication Date

7-16-2009

Department

Chemistry and Biochemistry

School

Mathematics and Natural Sciences

Abstract

A practical mass spectrometry-based enantioselectivity assay is presented which makes use of enantiomerically enriched, but not enantiomerically pure, probe molecules readily obtained from esterase hydrolysis of prochiral malonates. The technique presented here allows us to recycle materials obtained from esterase hydrolysis which give substantial. but synthetically insufficient, enantiomeric excess as probe molecules in an enantioselectivity assay. The enantiomerically enriched products are esterified using deuterium-labelled alcohol. The enantiomeric excess is measured using mass spectrometry (LC-MS and LDI) by measuring the D-5/H-5 ratio in the resulting products obtained from an enzymatic hydrolysis. The D-5/H-5 ratio is corrected to account for the enantiomeric purity of the probe. Herein we report the results obtained from Pig Liver Esterase hydrolyses of prochiral malonate esters and outline the strengths and limitations of this approach to enantioselectivity determinations. This assay strategy was able to identify reaction conditions that led to an improvement in ee from 70% ee to >97% ee in the PLE-catalyzed hydrolysis of a prochiral malonate used to prepare unnatural serine analogues. (C) 2009 Elsevier Ltd. All rights reserved.

Publication Title

Tetrahedron-Asymmetry

Volume

20

Issue

13

First Page

1476

Last Page

1486

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