Synthesis of Multideuterated Dehydroepiandrosterone and Related 16, 17-Ketols

Abstract

Two synthetic routes leading to C-2, C-4 and C-6 deuterium-labeled dehydroepiandrosterone have been developed. d₄-Dehydroepiandrosterone was prepared from testosterone by way of the 2, 2, 4, 6-d₄-Δ^{3, 5}-dien-3-ol acetate. Alternatively, synthesis of d₅-dehydroepiandrosterone was carried out employing 3β-hydroxy-5α-androstane-6, 17-dione silyl ether as a key intermediate. Deuterium labeling was attained by reduction of the 6-oxo group with lithium aluminum deuteride and perdeuteration of active methylene groups adjacent to the 3-oxo group. In addition, d₅-dehydroepiandrosterone was transformed into the epimeric 16-hydroxy-17-ketones and 17β-hydroxy-16-ketone.