Syntheses of optically active citronellol, citronellal, and citronellic acid by microbial oxidation and double coupling system in an interface bioreactor

We have already reported that (RS)-Citronellol [(RS)-1] can be optically resolved via a transacetylation with acetyl coenzyme A [acetyl-CoA] by the aid of alcohol acetyltransferase [AATFase] in Pichia kluyveri IFO 1165, which we have referred to as a double coupling system (E value, 30 to 40). In this system, although (R)-1 is obtained at over 98% ee, (S)-Citronellyl acetate [(S)-2] is prepared at 70 to 80% ee. In this article, we report on the conversion of (R)-1 to (R)-Citronellal [(R)-3] and (R)-Citronellic acid [(R)-4] in high yield without racemization by the aid of Rhodococcus equi JCM 6817 and Geotrichum candidum JCM 01747, respectively. On the other hand, the low ee of (S)-1 (78% ee) prepared via the alkaline hydrolysis of (S)-2 is converted to optically active (S)-1 and (S)-4 in high yield with a repeated double coupling system with P. kluyveri IFO 1165 and via enantioselective oxidation with Candida viswanathii IFO 10321, respectively. Thus, five optically active terpenoids related to citronellol, except for (S)-3, were efficiently synthesized via microbial transformations in an interface bioreactor.