Microbial reduction of 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1- piperazinyl]butan-1-one.
Among various micro-organisms screened for the stereoselective reduction of 4-chloro-1-(4-fluorophenyl)butan-1-one (1), Hansenula polymorpha [American Type Culture Collection (A.T.C.C.) 26012 and 86014], Nocardia salmonicolor [Squibb Culture (S.C.) 6370], Arthobacter simplex (A.T.C.C. 6949), Mycobacterium vaccae (A.T.C.C. 29678), Candida boidinii (A.T.C.C. 13821) and Saccharomyces cerevisiae (A.T.C.C. 13792) reduced compound 1 to the corresponding (R)-(+)-alcohol (2). In contrast, Lactobacillus kefir (A.T.C.C. 35411), Pullularia pullulans (A.T.C.C. 16623), Trigonopsis variabilis (A.T.C.C. 10679) and Cunninghamella echinulata (A.T.C.C. 26269) reduced compound 1 to the (S)-(-)-alcohol (2). When 1-(4-fluorophenyl)-4-(1-piperazinyl)butan-1-one (3) was used as substrate for the reduction, only Nocardia globerula (A.T.C.C. 12505) and Saccharomyces cerevisiae (A.T.C.C. 13792) converted compound 3 into the corresponding (R)-(+)-alcohol (4). Organisms which reduced compound 1 were inactive for the reduction of compound 3. 1-(4-Fluorophenyl)-4-[4-(5-fluoro-2- pyrimidinyl)butan-1-one (5) was reduced to the corresponding (R)-(+)-alcohol (6) by Mortierella ramanniana (A.T.C.C. 38191) and to the (S)-(-)-alcohol (6) by Pullularia pullulans (A.T.C.C. 16623). (R)-(+)-compound 2 and compound 4 are key chiral intermediates in the total chemical synthesis of (R)-(+)-compound 6, an effective antipsychotic agent under development at Bristol-Myers Squibb. A single-stage (fermentation/biotransformation) process and two-stage (fermentation and subsequent biotransformation by cell suspensions) process were developed for the stereoselective reduction of compound 5 to (R)-(+)-compound 6 by Mortierella ramanniana (A.T.C.C. 38191). In both processes, the reaction yield of 98% and the optical purity of 99.4% were obtained for (R)-(+)-compound 6. The enzyme which catalysed the reduction of compound 5 to (R)-(+)-compound 6 was purified to homogeneity. The purified protein consisted of a single polypeptide of 29 kDa.
- 원문이 없습니다.
- International Union of Biochemistry and Molecular Biology : 저널
유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.
원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.
NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.
- 이 논문과 함께 출판된 논문 + 더보기