TY - JOUR
T1 - Synthesis of enantiomerically enriched drug precursors and an insect pheromone via reduction of ketones using commercially available carbonyl reductase screening kit “Chiralscreen® OH”
AU - Nagai, Toshiya
AU - Sakurai, Saki
AU - Natori, Naoki
AU - Hataoka, Manaka
AU - Kinoshita, Takako
AU - Inoue, Hiroyoshi
AU - Hanaya, Kengo
AU - Shoji, Mitsuru
AU - Sugai, Takeshi
N1 - Funding Information:
We thank Dr. Motoko Hayashi, Daicel Co., for her advice on the use of “Chiralscreen® OH” and Mr. Shoji Miyamoto, Daicel Corp, for his information on the HPLC analysis of stereoisomers. Generous gift of crystalline NaOCl-5H2O and valuable suggestions by Drs. Yukihiro Sugiyama and Kiyhoshi Watanabe, Nippon Light Metal, Co. Ltd. are acknowledged with thanks. This work was supported by Global Science Campus, Japan Science and Technology Agency, Japan and M. H. and T. K. thank for the participation of this program. This work was also supported both by a Grant-in-Aid for Scientific Research (No. 26450143) and Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and is gratefully acknowledged with thanks.
Funding Information:
We thank Dr. Motoko Hayashi, Daicel Co., for her advice on the use of “Chiralscreen® OH” and Mr. Shoji Miyamoto, Daicel Corp, for his information on the HPLC analysis of stereoisomers. Generous gift of crystalline NaOCl-5H 2 O and valuable suggestions by Drs. Yukihiro Sugiyama and Kiyhoshi Watanabe, Nippon Light Metal, Co. Ltd. are acknowledged with thanks. This work was supported by Global Science Campus, Japan Science and Technology Agency , Japan and M. H. and T. K. thank for the participation of this program. This work was also supported both by a Grant-in-Aid for Scientific Research (No. 26450143 ) and Platform for Drug Discovery, Informatics, and Structural Life Science from the Ministry of Education, Culture, Sports, Science and Technology, Japan , and is gratefully acknowledged with thanks.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Commercially available “Chiralscreen® OH” starter kit containing five types of carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction of several aromatic and aliphatic ketones to obtain enantiomerically enriched drug precursors and an insect pheromone. Almost stereochemically pure secondary alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)-rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked well with ketones containing at least one non-bulky substituent at the carbonyl group. The diverse stereochemical preference of the above five carbonyl reductases was clarified.
AB - Commercially available “Chiralscreen® OH” starter kit containing five types of carbonyl reductases (E001, E007, E031, E039, and E078) was used for the reduction of several aromatic and aliphatic ketones to obtain enantiomerically enriched drug precursors and an insect pheromone. Almost stereochemically pure secondary alcohols, used in the synthesis of drugs such as (R)-rasagiline mesylate, (S)-rivastigmine, (R)-chlorphenesin carbamate, and (R)-mexiletine, and the insect pheromone (4S,5R)-sitophilure, were conveniently obtained. The enzymes worked well with ketones containing at least one non-bulky substituent at the carbonyl group. The diverse stereochemical preference of the above five carbonyl reductases was clarified.
KW - Asymmetric reduction
KW - Carbonyl reductase
KW - Enzyme library
KW - “Chiralscreen® OH”
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U2 - 10.1016/j.bmc.2017.03.067
DO - 10.1016/j.bmc.2017.03.067
M3 - Article
C2 - 28506583
AN - SCOPUS:85018874797
SN - 0968-0896
VL - 26
SP - 1304
EP - 1313
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 7
ER -