BioChem - DOS

Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

Organic process research & development

Fryszkowska, Anna; Peterson, Justine; Davies, Nichola L.; Dewar, Colin; Evans, George; Bycroft, Matthew; Triggs, Neil; Fleming, Toni; Gorantla, Srikanth Sarat Chandra; Hoge, Garrett; Quirmbach, Michael; Timmanna, Upadhya; Reddy Poreddy, Srinivas; Kumar Reddy, D. Naresh; Dahanukar, Vilas; Holt-Tiffin, Karen E.

<P>Dehydroepiandrosterone (DHEA, <B>2</B>) 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&minus;4 In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (<B>2</B>) and DHEA acetate (<B>3</B>) from 4-androstene-3,17-dione (4-AD, <B>1</B>). Crucial to success was the identification of a ketoreductase from <I>Sphingomonas wittichii</I> for the highly regio- and stereoselective reduction of the C3-carbonyl group of 5-androstene-3,17-dione (<B>5</B>) to the required 3&beta;-alcohol (<B>2</B>, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L).</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/oprdfk/2016/oprdfk.2016.20.issue-8/acs.oprd.6b00215/production/images/medium/op-2016-00215r_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/op6b00215'>ACS Electronic Supporting Info</A></P>

2016

American Chemical Society

acs-specific: authorchoice/editors choice usage agreement

1083-6160

1520-586x

20

8

pp.1520-1528

10.1021/acs.oprd.6b00215

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART76142696

https://pubs.acs.org/doi/pdf/10.1021/acs.oprd.6b00215