Total Synthesis of Marine Alkaloids Cystodytins A-K.

Abstract

The total synthesis of marine alkaloids cystodytins A-K has been accomplished in five to six steps starting from commercially available compounds. The highlights of the synthesis include an oxidative amination-cyclization of tryptamine and para-hydroquinones to build a tetracyclic pyridoacridinone ring with different side chains and a copper(II)-catalyzed enantioselective Henry reaction to construct an oxygenated stereogenic carbon center. For the first time, the absolute configuration of the stereogenic centers embedded in cystodytins D-I and K was established as R. Moreover, the stereochemistry of the olefin unit in the side chain of cystodytins H and I was revised to the Z configuration from the originally assigned E configuration.