Preparing drospirenone comprises reacting methyleneprasterone with strong base and with lithium and bromopropyl-trimethylsilylether, removing trimethylsilyl-protecting group and oxidatively cyclizing methylene-hydroxy-(propanol)-prasterone

摘要

Preparing drospirenone comprises: reacting methyleneprasterone (MEP) with strong base and with e.g. lithium and 1-bromopropyl-3-trimethylsilylether to give methylene-hydroxy-(propyl-3-trimethylsilyloxy)-prasterone (MTPP); removing trimethylsilyl-protecting group to give methylene-hydroxy-(propan-3-ol)-prasterone (MHPP); oxidatively cyclizing MHPP to methyleneandrost-4-en-3-on-spirolactone (MADO-lactone); enolizing MADO-lactone to methoxy-methyleneandrost-dien-on-spirolactone (MOMA-lactone), oxidizing to methyleneandrost-dien-on-spirolactone (MDD-lactone); and subsequently adding methylene. Preparing drospirenone comprises: reacting 15,16-methyleneprasterone (MEP) with a strong base and subsequently reacting the reaction product with lithium or butyl lithium and 1-bromopropyl-3-trimethylsilylether to obtain 15,16-methylene-17beta -hydroxy-17alpha -(propyl-3-trimethylsilyloxy)-prasterone (MTPP); removing the trimethylsilyl-protecting group to 15,16-methylene-17beta -hydroxy-17alpha -(propan-3-ol)-prasterone (MHPP); oxidatively cyclizing (MHPP) to 15,16-methyleneandrost-4-en-3-on-17(S)-spirolactone (MADO-lactone); enolizing (MADO-lactone) 3-methoxy-15,16-methyleneandrost-4,6-dien-3-on-17(S)-spirolactone (MOMA-lactone), subsequently oxidizing to 15,16-methyleneandrost-4,6-dien-3-on-17(S)-spirolactone (MDD-lactone); and subsequently adding methylene to drospirenone. Independent claims are included for MTPP and its diastereomeric pure form. ACTIVITY : Contraceptive; Antiandrogenic. MECHANISM OF ACTION : None given.