Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has bee n accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 1 0% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3 and anhydrom acrosalhine-methine 4 in 12% and 14% overall yield, respectively. A conveni ent synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N-a-H, N-b-benzyl tetracyclic ketone 15a via the a symmetric Pictet-Spengler reaction on a multihundred-gram scale has been de veloped. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and t he intramolecular rearrangement to form ring-E and an N-b-benzy/N-b-methyl transfer reaction also served as key steps. This general approach can now b e utilized for the synthesis of macroline/ sarpagine related indole alkaloi ds and their antipodes for biological screening.