Abstract: Drospirenone (6β,7β;15β,16β-dimethylen-3-oxo-17α-pregn-4-ene-21,17-carbolact- one) is a novel synthetic progestogen with antimineralocorticoid and antiandrogenic activity as well as a pharmacological profile similar to that of natural progesterone. The development of 6β,7β-Methylene in drospirenone has received considerable attention. A facile approach to 6β,7β-Methylene in drospirenone was reported and the target compound drospirenone was conveniently synthesized from 15β,16β-methylen-3-oxo-17α-pregn-4,6-dien-21,17-carbolactone by reduction with sodium borohydride, epoxidation with metachloroperbenzoic acid, reductive ring cleavage with lithium-aluminum hydride, Simmons-Smith addition, and oxidation with CrO3 in series. The reductive ring cleavage of the intermediate 4β,5β-epoxy-15β,16β-methylen- 17α-pregn-6-en-3β-ol-21,17-carbolactone came out to be C4-O cleavage to give cis product 15β,16β-methylen-17α-pregn-6-en-3β,5β-diol-21,17-carbolactone in the yield of 91.4%, resisting to C5-O cleavage, which is the key to afford the needed unit 5β-hydroxyl-6-ene for highly β-steroselective Simmons-Smith addition to give the target unit 6β,7β-methylene. The chemical structures of intermediates and target product were characterized by IR, 1H NMR, MS, and Elemental analysis.

Key words: Drospirenone, Cyclopropanation, epoxide cleavage, Simmons-Smith Addition, LiAlH4 Reduction