Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis

Abstract

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 C3carbonyl 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).

A Bio-Inspired Lanthanum-Ortho Quinone Catalyst for Aerobic Oxidation of Alcohol

“…Reaction condition: 0.5 mmol scale, LaI3 2%, o-Q 4%, DCM/MeCN 1:1, 1 ml. Characterization was in consistent with previous literature31 1. H NMR (400 MHz, CDCl3) δ 5.75 (s, 1H), 2.32 (m, 5H), 1.95 (m, 4H), 1.84 (m, 1H), 1.67 (m, 3H), 1.52 (m, 1H), 1.41 (m, 1H), 1.26 (m, 2H), 1.22 (s, 3H), 1.07 (m, 1H), 0.97 (m, 1H), 0.92 (s, 3H).…”

Metal-Free, Redox-Neutral, Site-Selective Access to Heteroarylamine via Direct Radical–Radical Cross-Coupling Powered by Visible Light Photocatalysis

“…4-Aminophenyl- d -galactopyranoside, a biologically relevant glycoside, afforded the desired product in 35% yield ( 82c ). Two other kinds of bioactive molecules derived from mestanolone and dehydroepiandrosterone, respectively, members of the anabolic androgenic class of steroids, showed good reactivities to produce the corresponding products in 56% ( 83c ) and 45% ( 84c ) yields. These examples emphasize the synthetic prospect of this metal-free amination strategy in the pharmaceutical field.…”

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

“…Advances in synthetic biology and the increasing importance of methods of sustainable chemistry have brought chemoenzymatic approaches for obtaining natural products, or derivatives thereof, with complex structure into focus [1]. Various enzymatic or semisynthetic methods have also been exploited in the synthesis of steroids [2][3][4]. A more challenging synthesis of secosteroids with unique broken tetracyclic carbon skeletons and abeo-steroids with migrated bonds has received attention only recently [5,6].…”