A Designed Chemoenzymatic Route for Efficient Synthesis of 6-Dehydronandrolone Acetate: A Key Precursor in the Synthesis of C7-Functionalized Steroidal Drugs

Abstract

Dehydronandrolone acetate (3) is a crucial precursor for the synthesis of C7-functionalized steroidal drugs. However, the current production method involves a laborious and environmentally unfriendly five-step chemical process, resulting in a low efficiency. To overcome this, we report a chemoenzymatic strategy, involving a one-pot biocatalytic C7β-hydroxylation/C17β-ketoreduction of 19-norandrostenedione (1) by combination of P450 monooxygenase and 17-ketosteroid reductase to generate C7β-hydroxynandrolone (2) as an intermediate, followed by a one-pot chemical dehydration and esterification to form 3. Impressively, the gram-scale synthesis of 3 was achieved with 93% isolated yield, which outperforms the traditional chemical approach (68% yield), thereby signaling great potential for industrial applications.