Potential Antiinflammatory Agents. V. Synthesis of Metabolites of 6-Chloro-5-cyclohexylindan-1-carboxylic Acid (TAI-284) using Microbiological Hydroxylation

Abstract

Microbiological hydroxylation of 6-chloro-5-cyclohexylindan-1-carboxylic acid (TAI-284), a new potent antiinflammatory agent, with Penicillium concavo-rugulosum IFO 6226 gave 6-chloro-5-(trans-4'-hydroxycyclohexyl) indan-1-carboxylic acid (1), one of the main metabolites of TAI-284 in rats, in 71% yield. From this product two other metabolites, the corresponding 4'-oxo and cis-4'-hydroxy derivatives (4 and 2), were derived chemically. Catalytic hydrogenation of the 4'-oxo compound (4) over PtO₂ afforded the unexpected trans alcohol (1), but reduction of 4 with trimethylphosphite and iridium tetrachloride in aqueous isopropanol gave the desired cis alcohol (2) in 69% yield.