Step-Economic Total Synthesis of Melosatin A from Eugenol

An efficient and straightforward route toward the isatin-typenaturalproduct melosatin A is reported, employing a trisubstituted anilineas 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-metathesiswith 4-phenyl-1-butene and the simultaneous reduction of olefin andnitro groups. The final step, a Martinet cyclocondensation of thekey aniline with diethyl 2-ketomalonate, provided the natural productwith 68% yield.

Automated summary

An efficient and straightforward route to synthesize the isatin-type natural product melosatin A was reported. A trisubstituted aniline was used as a key intermediate, which was synthesized in 4 steps and yielded 60% overall. The final step involved the Martinet cyclocondensation of the key aniline with diethyl 2-ketomalonate, resulting in a 68% yield of the natural product.