Bioinspired Syntheses of Kuanoniamine D and Shermilamine B

We describe a bioinspired approach to the synthesis of the sulfur-containing marine pyridoacridine alkaloids kuanoniamine D and shermilamine B. The reaction sequence introduces a biogenic thia-substituent to N-acetyldopamine early in the overall pathway, mimicking the known chemistry of pheomelanin/trichochrome pigment biosynthesis. Subsequent oxidative coupling with kynuramine elaborated the pyridoacridine core, affording the target natural products, spectroscopic data of which were in excellent agreement with those reported for the isolated natural products. The use of mild reaction conditions will enable structure-activity studies of these bioactive alkaloids and open new avenues for the biomimetic synthesis of other structurally related natural products.