Regio‐ and Stereoselective Oxidation of Styrene Derivatives to Arylalkanoic Acids via One‐Pot Cascade Biotransformations

Abstract

AbstractGreen and selective oxidation methods are highly desired in chemical synthesis and manufacturing. In this work, we have developed a biocatalytic method for the regio‐ and stereoselective oxidation of styrene derivatives into arylacetic and (S)‐2‐arylpropionic acids via a one‐pot epoxidation–isomerization–oxidation sequence. This was done via the engineering of Escherichia coli (StyABC‐EcALDH) coexpressing styrene monooxygenase (SMO), styrene oxide isomerase (SOI) and aldehyde dehydrogenase (EcALDH) as an active and easily available whole‐cell catalyst. Regioselective oxidation of styrene and 11 substituted styrenes using the E. coli cells was performed in a one‐pot set‐up, producing 12 phenylacetic acids in both high conversion and high yield. Engineering of E. coli (StyABC‐ADH9v1) coexpressing SMO, SOI and ADH9v1 (a mutated alcohol dehydrogenase) led to biocatalysts capable of regio‐ and stereoselective oxidation of α‐methylstyrene derivatives to the corresponding chiral acids. One‐pot asymmetric synthesis of 4 (S)‐2‐arylpropionic acids was achieved in good conversion and excellent ee with the E. coli cells. This is a new type of asymmetric alkene oxidation to give chiral acids with no chemical counterpart thus far. The cascade bio‐oxidation operates under mild conditions, uses molecular oxygen, exhibits very high regio‐ and enantioselectivity, and gives high conversion, thus providing a green and efficient method for the synthesis of arylacetic acids and (S)‐2‐arylpropionic acids directly from easily available styrenes.magnified image