Efficient Synthesis of a Key Intermediate of DV-7751 via Optical Resolution or Microbial Reduction

Abstract

Two efficient and practical methods of synthesis of the C-10 substituent of DV-7751 (1), a novel quinolone carboxylic acid, were established. The first method utilizes an optical resolution of racemic 8-amino-6-benzyl-6-azapiro[3.4]octane (13), while the second employs an enantioselective microbial reduction of 6-benzyl-5, 8-dioxo-6-azaspiro[3.4]octane (8b). The enantiomeric excess of (S)-8-amino-6-benzyl-6-azaspiro[3.4]octane (11) with each method of synthesis is greater than 96%.