Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

详细信息    查看全文

• 作者：Anna Fryszkowska ; Justine Peterson ; Nichola L. Davies ; Colin Dewar ; George Evans ; Matthew Bycroft ; Neil Triggs ; Toni Fleming ; Srikanth Sarat Chandra Gorantla ; Garrett Hoge ; Michael Quirmbach ; Upadhya Timmanna ; Srinivas Reddy Poreddy ; D. Naresh Kumar Reddy ; Vilas Dahanukar ; Karen E. Holt-Tiffin
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：August 19, 2016
• 年：2016
• 卷：20
• 期：8
• 页码：1520-1528
• 全文大小：418K
• 年卷期：0
• ISSN：1520-586X

文摘

Dehydroepiandrosterone (DHEA, 2) is an important endogenous steroid hormone in mammals used in the treatment of a variety of dysfunctions in female and male health,1 as well as an intermediate in the synthesis of steroidal drugs, such as abiraterone acetate which is used for the treatment of prostate cancer.2−4 In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (2) and DHEA acetate (3) from 4-androstene-3,17-dione (4-AD, 1). Crucial to success was the identification of a ketoreductase from Sphingomonas wittichii for the highly regio- and stereoselective reduction of the C3-carbonyl group of 5-androstene-3,17-dione (5) to the required 3β-alcohol (2, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L).