Step-Economic Total Synthesis of Melosatin A from Eugenol

BOLIVAR ÁVILA, SANTIAGO J.; LEDESMA, GABRIELA N.; KAUFMAN, TEODORO S.; TESTERO, SEBASTIÁN A.; LARGHI, ENRIQUE L.

ACS Omega

American Chemical Society

Año: 2023 vol. 8 p. 23174 - 23181

An efficient and straightforward route toward the isatin-type natural product melosatin A is reported, employing a trisubstituted aniline as a key intermediate. The latter was synthesized in 4 steps and 60% overall yield from eugenol, through its regioselective nitration, sequentially followed by a Williamson methylation, an olefin cross-metathesis with 4-phenyl-1-butene and the simultaneous reduction of olefin and nitro groups. The final step, a Martinet cyclocondensation of the key aniline with diethyl 2-ketomalonate, provided the natural product with 68% yield.