Total Synthesis of Scholarisine K and Alstolactine A

The first asymmetric total syntheses
of scholarisine K and alstolactine
A have been accomplished. Our syntheses feature (1) ring closure metathesis
and an intramolecular Heck reaction to construct the 1,3-bridged [3,3,1]
bicycle (C–D ring), (2) intramolecular alkylation followed
by Fischer indolization to form the basic skeleton of akuammilines,
and (3) bioinspired, acid-promoted epoxide opening/lactonization to
generate the second lactone ring of alstolactine A. These results
provide evidence of a biogenetic relationship between scholarisine
K and alstolactine A, which should facilitate the preparation of other
akuammiline-type natural products and their derivatives for functional
studies.