8 (±)-Cepharamineの合成

抄録

Total synthesis of cepharamine (3), which is closely related in skeleton to morphinan (1) and the functionally least complicated member of hasubanan alkaloids, was attempted. The synthesis of the skeletal ring system, (±)-3,4-dimethoxy-N-methyl-hasubanan (13) has been reported in a previous publication. In the present synthesis, the Robinson annelation reaction; the route (b), the synthesis of the compound (20) from the keto nitrile (15); was successfully modified. Direction of enolmethylation of the diketones; the compound (29) possessing the lactam heterocycle and the compound (34) possessing the ethanamine bridge; was examined and it was shown that enolmethylation of the diketone (29) with MeOH-BF_3 brought the compound into the direction favorable to the cepharamine synthesis. Partial demethylation, followed by acetylation and then deketalization gave the ketoacetate (38). Successive treatment of the compound (38) with Br_2 and NaOAc in AcOH afforded the diketone (39), which was enolmethylated with MeOH-BF_3 to give oxocepharamine acetate (40). Lithium aluminum hydride reduction of the compound (40), followed by oxidation with DMSO gave (±)-cepharamine which was found to be identical with natural cepharamine in terms of i.r., n.m.r., and mass spectra and t.l.c. behavior.