Removal of the C 4 methyl groups from triterpenoids. Conversion of lanosterol into 14α-Methylcholesta-4,8-dien-3-one and the modification of ring A of methyl glycyrrhetinate

Abstract

14α-Methylcholesta-4,8-dien-3-one (9a) has been synthesized from lanosterol by a route involving the ?abnormal? Beckmann rearrangement of the oxime of 5α-lanost-8-en-3-one to the 3,4-seco nitrile (1a), from which the steroidal ring A was formed via the 3,5-dioxo 4,5-seco intermediate (8a). The formation of (8a) from the seco nitrile (1a) was readily achieved in a high-yielding sequence, which entailed stepwise degradation of the isopropenyl group, protection of the introduced 5- oxo function, and reaction of the cyano group with a Grignard reagent. The application of the above route to the modification of ring A of methyl glycyrrhetinate has also been investigated. Although the required triketone (8b) could be obtained, the method was rather low- yielding due to attack by the Grignard reagent on (11b) occurring at both C3 and C 11.