Synthesis of enantiomerically enriched drug precursors and an insect pheromone via reduction of ketones using commercially available carbonyl reductase screening kit "Chiralscreen® OH"

Toshiya Nagai, Saki Sakurai, Naoki Natori, Manaka Hataoka, Takako Kinoshita, Hiroyoshi Inoue, Kengo Hanaya, Mitsuru Shoji, Takeshi Sugai

研究成果: Article

6 引用 (Scopus)

抄録

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 (4. S,5. R)-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.

元の言語English
ジャーナルBioorganic and Medicinal Chemistry
DOI
出版物ステータスAccepted/In press - 2017 1 14

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Alcohol Oxidoreductases
Rivastigmine
Pheromones
Prodrugs
Ketones
Insects
Screening
Mexiletine
Mesylates
Starters
Alcohols
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

これを引用

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abstract = "Commercially available {"}Chiralscreen{\circledR} 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 (4. S,5. R)-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.",
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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

PY - 2017/1/14

Y1 - 2017/1/14

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 (4. S,5. R)-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 (4. S,5. R)-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 - "Chiralscreen® OH"

KW - Asymmetric reduction

KW - Carbonyl reductase

KW - Enzyme library

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