Asymmetric Total Synthesis of Gymnothespirolignan A via a Bioinspired Double Cyclization Approach

The first asymmetric total synthesis
of gymnothespirolignan A is
disclosed in 11 steps. The salient feature of the synthesis is construction
of the spirocyclic moiety through a bioinspired acid-promoted double
cyclization of an acyclic gymnothebutyllignan A-like precursor, which
involves a deprotection, hemiketalization, dehydrative oxonium formation,
and Friedel–Crafts cyclization cascade transformation. This
study provides a general approach to the asymmetric syntheses of novel
spirocyclic gymnothelignans.