FK409, a novel vasodilator isolated from the acid-treated fermentation broth of Streptomyces griseosporeus. III. Reaction mechanism and synthesis.

FK409 (1), a novel vasodilator, is a semi-artificial fermentation product of Streptomyces griseosporeus No. 16917, which was cultured in a medium containing nitrate. And the acid-treatment of the broth is essential for the generation of FK409. FK409 was considered to be formed via a novel synchronous nitrosation-nitration reaction of FR-900411 (2) which was produced by the strain as a precursor of FK409. The conversion of FK-900411 to FK409 proceeded under acidic conditions with nitrite formed by microbial reduction of nitrate. Total synthesis of FK409 was achieved starting from (E)-2-ethyl-2-butenal (3) via a nitrosation reaction of FR-900411 (2) as a key step.