Synthetic studies in the Veratrum alkaloid series. II. The total synthesis of verarine, veratramine, jervine, and veratrobasine

Coupling of 3β-acetoxy-5α-etiojerv-12(13)-en-17-one (1) with the lithio derivative of 2-ethyl-5-methylpyridine provides the crucial intermediate (3) for the subsequent elaboration to verarine. Aromatization of 3 to 4 and reduction of the latter provides a mixture from which N-acetyl-5α,6-dihydroverarine (11) was isolated. Subsequent introduction of the 5,6-double bond in the latter and removal of the N-acetate function completed the synthesis of verarine (31). In a similar sequence of reactions employing 1 and the lithio derivative of 2-ethyl-3-methoxy-5-methyl-pyridine, the resultant intermediate (54), was elaborated to 5α,6-dihydroveratramine (56). Due to known conversions of the latter to veratramine (14), jervine (32), veratrobasine (33), and 11-deoxojervine (34), the formal total synthesis of these natural products is complete