Enantioselective Synthesis of a Key Intermediate of 20(S)-Comptothecin via and Enzyme-Catalyzed Resolution

Abstract

The key intermediate of a 20(S)-camptothecin 1 synthesis was obtained in a highly enantioselective fashion using an enzyme-catalyzed resolution. A commercially available protease was found to exhibit the highest enantioselectivity with moderate activity, and (S)-ethyl 2-acetoxy-2[6-(acetoxymethyl)-1, 1-(ethylenedioxy)-5-oxo-1, 2, 3, 5-tetrahydroindolizin-7-yl]butanoate 7c of 98% e.e. was obtained as the remaining substrate.