General Approach for the Synthesis of Ajmaline/Sarpagine Indole Alkaloids: Enantiospecific Total Synthesis of (+)-Ajmaline, Alkaloid G, and Norsuaveoline via the Asymmetric Pictet−Spengler Reaction

A general approach (oxyanion-Cope strategy) for the synthesis of sarpagine/ajmaline indole alkaloids has been developed. (+)-Ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3 have been synthesized from d-(+)-tryptophan in enantiospecific fashion via the asymmetric Pictet−Spengler reaction and a stereocontrolled oxyanion-Cope rearrangement as key steps. The synthesis of these indole alkaloids employed a stereospecific Pictet−Spengler/Dieckmann protocol to prepare the key intermediate, (−)-Nb-benzyl tetracyclic ketone (7a or 7b). This ketone was converted into α,β-unsaturated aldehyde (8a or 8b) and further transformed into (+)-ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3. It was also found that reduction of 29 can be done stereospecifically to form the 2-epidiacetylajmaline derivative 30 which has the same configuration at C(2) as that of quebrachidine and of the bisindole alstonisidine. The ring closure reaction (from 27 to 28) to form the sarpagine skeleton was completed in 91% yield. It s...