Progress toward the total synthesis of Alstonia indole alkaloids peraksine and macrosalhine bromide as well as the formal total synthesis of secotalcarpine and macrocarpine B

ORGN 743

Rahul V. Edwankar, edwankar@uwm.edu, Chitra R. Edwankar, csawant@uwm.edu, and James M. Cook, capncook@uwm.edu. Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, 3210 N. Cramer St., Milwaukee, WI 53211
Nine alkaloids belonging to the ajmaline-sarpagine series bearing a chiral C-19 methyl group have been isolated. Peraksine (1) and Macrosalhine bromide (2) belong to this group of alkaloids. The core tetracyclic ketone (common to macroline/sarpagine alkaloids) was employed as the starting point for the total synthesis of 1 and 2. This tetracyclic ketone can be synthesized from D (+)-tryptophan on a multihundred gram scale. The chiral methyl group was introduced into the tetracyclic system by alkylating the Nb-nitrogen with an acetylenic tosylate. Cyclisation was achieved by a palladium catalyzed, enolate coupling to provide the desired pentacyclic framework. This pentacyclic ketone could then be converted into (1) and (2) by regiospecific hydoboration, followed by a hemiacteal ring formation. Conversion of the sarpagine system into the macroline framework can be achieved via a retro-Michael reaction to provide secotalcarpine (3) and macrocarpine B (4).