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.
Hino
M
M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Takase
S
S
Itoh
Y
Y
Uchida
I
I
Okamoto
M
M
Kohsaka
M
M
Aoki
H
H
Imanaka
H
H
D000466:Alkadienes / Q000138:chemical synthesis / Q000378:metabolism*; D005285:Fermentation; D015394:Molecular Structure; D009574:Nitro Compounds / Q000378:metabolism*; D013302:Streptomyces / Q000378:metabolism*; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000378:metabolism*
D000466:Alkadienes; D009574:Nitro Compounds; D014665:Vasodilator Agents; C061873:FR 900411; C061872:FK 409