Four-Component Construction of Coumarin-Fused Pyrrolo[2,1-a]isoquinoline: Expedient Synthesis of Lamellarins and Their Regioselective Demethylation

Construction of the coumarin-fused pyrrolo[2,1-a]isolquinoline skeleton was realized through a four-component reaction between isoquinoline, ethyl bromoacetate, o-hydroxybenzaldehyde and nitromethane. This methodology was further extended to the synthesis of lamellarin D trimethyl ether and a formal synthesis of lamellarin D. The controlled demethylation of lamellarin D trimethyl ether yielded dihydroxy and tetrahydroxy lamellarin analogues regioselectively.

Automated summary

A novel synthetic method was developed for the synthesis of lamellarin D and its analogues, using a four-component reaction. Controlled demethylation of lamellarin D trimethyl ether yielded lamellarin analogues with different functional group positions.