Chemoenzymatic synthesis of 2-oxabicyclo[3.3.1]nonan-3-one enantiomers via microbial reduction by Absidia coerulea AM 93

Microbial enantioselective reduction of (±)-diethyl 2-(3-oxocyclohexyl)malonate (1) has been described. A screening test on twenty-four fungi strains was carried out. Most of the microorganisms preferred bioreduction of (+)-isomer of δ-ketoester (1) to (+)-trans δ-hydroxy ester (2) with the anti-Prelog selectivity. Biotransformation conditions using Absidia coerulea AM 93 were optimized with respect to the growth medium, temperature and pH. An effect of 48 chemical additives on the course of biotransformation was checked. (−)-Diethyl 2-((S)-3-oxocyclohexyl)malonate ((−)-1) (ee = 98%) and (+)-diethyl 2-((1R, 3R)-3-hydroxycyclohexyl)malonate ((+)-2) (ee = 99%) were isolated and subjected to chemical lactonization, leading to (+)-(1R, 5S)-2-oxabicyclo[3.3.1]nonan-3-one ((+)-3) and (−)-(1S, 5R)-2-oxabicyclo[3.3.1]nonan-3-one ((−)-3). The absolute configuration of product (−)-1 was confirmed by comparison of its optical rotation with the literature data. The absolute configuration the carbon atom bearing hydroxyl group in product (+)-2 was determined using the Mosher's ester.