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使用市售羰基还原酶筛选试剂盒“Chiralscreen® OH”还原酮合成对映体富集的药物前体和昆虫信息素。

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

机构信息

Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

Ichikawa Senior High School, 2-38-1, Motokitakata, Ichikawa 272-0816, Japan.

出版信息

Bioorg Med Chem. 2018 Apr 1;26(7):1304-1313. doi: 10.1016/j.bmc.2017.03.067. Epub 2017 Apr 1.

Abstract

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.

摘要

市售的“Chiralscreen® OH”起始试剂盒包含五种羰基还原酶(E001、E007、E031、E039 和 E078),可用于还原多种芳香族和脂肪族酮,以获得对映体富集的药物前体和昆虫信息素。几乎立体化学纯的仲醇,可用于合成药物,如(R)-雷沙吉兰甲磺酸盐、(S)-利伐斯的明、(R)-氯苯嗪氨基甲酸酯和(R)-美西律,以及昆虫信息素(4S,5R)-sitophilure,都可方便地获得。这些酶在含有羰基至少一个非庞大取代基的酮中效果良好。上述五种羰基还原酶的不同立体化学偏好得到了阐明。

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