Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A

The planning and implementation of an enantioselective
total synthesis of (+)-scholarisine A is presented. Key tactics employed
include a novel cyclization, consisting of a nitrile reduction coupled
with concomitant addition of the resultant amine to an epoxide; a
modified Fischer indolization; an oxidative lactonization of a diol
in the presence of an indole ring; and a late-stage cyclization to
complete the caged ring scaffold. The development of a possible “retro-biosynthetic”
approach to other members of the akuammiline alkaloid family is also
described.