Chemoenzymatic Synthesis of tert-Butyl ((3R, 6R)-6-methyl-piperidin-3-yl)carbamate: A Key Intermediate in Orexin Receptor Antagonist and IRAK4 Inhibitor

IF 1.9 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Zhe Zhang, Ying-Cong Liang, Tong Li, Chao-Lin Liu, Yun-Hu Zhao, Shan Li, Bing Gu, Lei Zhang
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引用次数: 0

Abstract

tert-Butyl ((3R,6R)-6-methylpiperidin-3-yl)carbamate is a pivotal pharmaceutical intermediate and active pharmacophore in drug synthesis, encompassing applications in orexin receptor antagonist and IRAK4 inhibitor. To date, a simple and efficient synthetic route remains a challenging issue for chemists in constructing chiral centers. In this study, we present a practical process for the preparation of tert-butyl ((3R,6R)-6-methylpiperidin-3-yl)carbamate, the key chiral intermediate via a chemoenzymatic strategy from commercially available ethyl N-Boc-D-pyroglutamate, which undergoes transamination-spontaneous cyclization process by transaminase (ATA) biocatalyst. Our study outlines a shortened-step streamlined procedure circumventing a significant amount of toxic chemicals and hazardous reaction conditions, and features cost-effective and high optical purity with >99.9% enantiomeric excess. The process features great prospect of industrialization application.

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来源期刊
ChemistrySelect
ChemistrySelect Chemistry-General Chemistry
CiteScore
3.30
自引率
4.80%
发文量
1809
审稿时长
1.6 months
期刊介绍: ChemistrySelect is the latest journal from ChemPubSoc Europe and Wiley-VCH. It offers researchers a quality society-owned journal in which to publish their work in all areas of chemistry. Manuscripts are evaluated by active researchers to ensure they add meaningfully to the scientific literature, and those accepted are processed quickly to ensure rapid online publication.
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