Step-Economic Total Synthesis of Melosatin A from Eugenol

Abstract

An efficient and straightforward route toward the isatin-type natural product melosatin A is reported, employing atrisubstituted aniline as a key intermediate. The latter was synthesized in 4 steps and 60% overall yield from eugenol, through itsregioselective nitration, sequentially followed by a Williamson methylation, an olefin cross-metathesis with 4-phenyl-1-butene andthe 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.