A synthesis of 1β-hydroxytestosterone, a metabolite of xenobiotic human cytochrome P450 enzymes, beginning with a borylation of boldione

Abstract

Xenobiotic cytochrome P450 enzymes have been shown to hydroxylate testosterone at various positions in the steroid backbone, including C1 to produce 1β-hydroxytestosterone. Despite the potential application to study the biochemistry of these enzymes, 1β-hydroxytestosterone is not commercially available. A synthesis of 1β-hydroxytestosterone from commercially available boldione (androst-1,4-dien-3,17-dione) was accomplished in eight steps. The key step to functionalize C1 was a borylation reaction catalyzed by an in situ generated copper carbene complex. The synthetic strategy reported will be used to access other biologically relevant C1-hydroxylated steroids to explore the biochemistry of drug metabolizing P450 enzymes.