Total synthesis of 6,8-dimethoxy-1,3-dimethylisoquinoline, a natural product and the heterocyclic core of bioactive naphthylisoquinoline alkaloids

GIRARDINI, JAVIER; CORTÉS IVAN; KAUFMAN TEODORO S.; BORINI ETICHETTI, CARLA M.; BRACCA A.

Conferencia; LatinXChem Twitter Conference; 2020

A facile and convenient approach toward the synthesis of 1,3-dimethyl-6,8-dimethoxyisoquinoline from phloroacetophenone is reported. The sequence entails the selective 2,4-di-O-methylation and further triflation of the phenolic starting material. This is followed by a Stille-type allylation, an allyl to propenyl isomerization, and the methoximation of the carbonyl moiety. A final microwaves-assisted 6π-azaelectrocylization completes the sequence. Functionalized derivatives on C-1 were also prepared. The heterocycles exhibited cytotoxic activity.