Biocatalytic Resolutions of Benzofuranone and Indole Derivatives

Drug precursors and intermediates leading to the synthesis of benzofuranone and indole type derivatives are very important field of science and pharmaceutical industry since their biological activities. Chemical synthesis of pure and enantioselective benzofuranone and indole derivatives are very difficult. It is important to synthesize easily enantiomerically pure benzofuranone and indole derivatives with high biological activity using biotransformation methods as enzymes and microbial cells for drug industry. In this study, first of all the chemoenzymatic synthesis of both enantiomers of pharmacologically interesting compound such as 4,5,6,7-tetrahydro-4-oxo-7,7-dimethyl benzofuran-5-yl acetate is synthesized starting from 7,7-dimethyl-6,7-dihydrobenzofuran-4(5H)-one by regioselective acetoxylation reaction. Enzyme catalyzed kinetic resolution of this racemic acetoxy derivative furnished the corresponding enantiomers of acetoxy and hydroxy derivatives in high enantiomeric excesses. In the second part of the study, 4,5,6,7-tetrahydro-4-oxo-7,7-dimethyl benzofuran-5-yl acetate is converted its indole derivative via benzyl amine, then enzyme-mediated kinetic resolution is applied. The α-acetoxy and α-hydroxy indole derivatives are obtained in good yields and high enantiomeric excesses. Furthermore, in this study the biotransformation of pharmacologically interesting compound such as 6,7-dihydro-5-hydroxy-7,7dimethyl-1H-indol-4(5H)-on is also obtained by using microorganisms.