Tackling the Spiro Tetracyclic Skeleton of Cyanogramide: Incorporation of a Hydantoin Moiety

Wang's enantioselective thiourea-catalyzed spiro-annulation paved the way to the first tetracyclic analog of the marine natural product cyanogramide from the actinobacterium Actinoalloteichus cyanogriseus. The synthesis comprises seven steps starting from an alkylidene indolinone. Installation of the (E)-styryl side chain faced a regiochemistry problem, circumvented by prior conversion to the hydantoin and employing Batey's conditions. Comparison of the ECD spectra of the spiro indoline pyrrolo[1,2-c]imidazole and cyanogramide confirmed the absolute configuration of the natural product.