Enantioselective Total Synthesis of Cotylenin A

A convergent enantio­selective
total synthesis of cotylenin
A is described. The A-ring fragment, prepared via the catalytic asymmetric
intra­molecular cyclopropanation developed in our laboratory,
and the C-ring fragment, prepared from a known chiral compound via
a modified acyl radical cyclization, were successfully assembled by
the Utimoto coupling reaction. The formidable carbocyclic eight-membered
ring of cotylenin A was efficiently constructed by a palladium-mediated
cyclization. All the hydroxy groups in the scaffold were stereo­selectively
introduced, and a modified reducing reagent, Me4NBH­(O2CiPr)3, has been developed.
The sugar moiety fragment was prepared via three consecutive carbon–oxygen
bond-forming reactions, and the glycosylation was accomplished using
Wan’s protocol.