Clascoterone: Introduction and Synthesis

Introduction of Clascoterone

Clascoterone (cortexolone 17α-proprionate), a novel androgen receptor inhibitor, obtained its first approval by the USFDA in August 2020. The drug was indicated for the topical treatment of acne vulgaris in patients 12 years of age and older. The API was developed as a 1% cream, which is currently marketed by the Italian pharmaceutical firm Cassiopea S.p.A. In Phase 3 clinical trials involving patients with acne vulgaris, the topical drug formulation demonstrated favorable efficacy and safety with low adverse event rates.

Synthesis of Clascoterone

Clascoterone is synthesised using dipropionate as raw material by chemical reaction. The specific synthesis steps are as follows:

The synthesis of clascoterone proceeded through a lipasecatalyzed chemoselective alcoholysis of the corresponding 17a,21-diester 102 in a single step. Dipropionate 102 was treated with a lipase from Candida cylandracea (CCL) using butanol as the acyl acceptor and toluene as the solvent, resulting in clascoterone in 99% yield.