Preparing drospirenone, useful as a component of hormonal contraceptives, comprises reacting dimethylen-androst-4-en-3,17-dione with o-(3-halopropionic acid)-trialkylester to give trialkoxypropyl-hydroxy-dimethylene-androst-4-en-3-one

摘要

Preparation of drospirenone (I) comprises either reacting 6,7,15,16-dimethylen-androst-4-en-3,17-dione (II) with o-(3-halopropionic acid)-trialkylester (III) to give 17alpha -(3,3,3-trialkoxypropyl)-17beta -hydroxy-6,7,15,16-dimethylene-androst-4-en-3-one (IV), and converting (IV); or reacting (II) with a halo-propionaldehyde acetal (V) to give 6,7,15,16-dimethylen-17beta -hydroxy-17alpha -(3,3-dialkoxypropyl)-androst-4-ene, converting (V) to dimethylen-17-spirol (VI) and subsequently oxidizing (VI). Preparation of drospirenone (I) comprises either reacting 6,7,15,16-dimethylen-androst-4-en-3,17-dione (II) with o-(3-halopropionic acid)-trialkylester of formula (X-CH 2-CH 2-C(OR) 3) (III) to give 17alpha -(3,3,3-trialkoxypropyl)-17beta -hydroxy-6,7,15,16-dimethylene-androst-4-en-3-one (IV), and converting (IV); or reacting (II) with a halo-propionaldehyde acetal of formula (X-CH 2-CH 2-CH(OR) 2) (V) to give 6,7,15,16-dimethylen-17beta -hydroxy-17alpha -(3,3-dialkoxypropyl)-androst-4-ene, converting (V) to dimethylen-17-spirol (VI) and subsequently oxidizing (VI). X : Cl, Br, I, mesylate, tosylate or triflate; and R : not defined. Independent claims are included for: (1) the preparation of 6beta ,7beta ,15beta ,16beta -dimethylen-androst-4-en-3,17-dione diastereomer comprising cyclopropanation between the positions 15 and 16 of the steroid nucleus containing double bonds of 6beta ,7beta -methylen-androst-4,15(16)-dien-3,17-dione; and (2) 6,7-methylen-androst-4,15-dien-3,17-dione. ACTIVITY : Antiandrogenic; Contraceptive. MECHANISM OF ACTION : None given.