A formal total synthesis of (-)-cephalotaxine

A formal total synthesis of(-)-cephalotaxine (1) has been achieved. The key step is an intramolecular aldol condensation of the diketone 9, which in t urn was obtained in three steps from the azabicyclic compound 6 derived fro m D-proline according to Seebach's procedure. Treatment of 9 with a catalyt ic amount of sodium 2-methyl-2-butanolate in benzene at room temperature ga ve the alpha,beta-unsaturated ketone 8 in 43% yield. Catalytic hydrogenatio n of 8 followed by reduction of the ketone 22 with sodium borohydride and a cetylation of the resulting alcohol 23 gave the acetoxy derivative 24, whic h, after deprotection, was acylated with (methylthio)acetic acid to give th e amide 26. Compound 26 was converted into optically active ketolactam 4 fo llowing the synthetic operations developed for the synthesis of the racemic compound.