Microbiological transformations. Part 45: A green chemistry preparative scale synthesis of enantiopure building blocks of Eliprodil: elaboration of ahigh substrate concentration epoxide hydrolase-catalyzed hydrolytic kinetic resolution process

The enantioselective hydrolysis of racemic para-chlorostyrene oxide 2 follo wing a typical 'green chemistry' procedure based on the use of two differen t Epoxide Hydrolases is described. This allows the preparation of both enan tiomers of 2 in very high enantiomeric purity. Furthermore, using a 'one-po t' sequential bi-enzymatic strategy enabling to overcome the 50% yield limi tation intrinsic to any resolution process, rac-2 could be transformed into nearly enantiopure (R)-3 with an overall yield as high as 93%. The methodo logy developed was based on the use of a biphasic reactor at high substrate concentration, which is highly desirable for any potential industrial proc ess. The obtained chirons are valuable building blocks for the synthesis of various biologically active targets, like (R)-Eliprodil. (C) 2001 Elsevier Science Ltd. All rights reserved.