Studies on proaporphine and aporphine alkaloids. Part V. Synthesis of (±)-glaziovine by 8,1′-ring closure of 1-benzylisoquinoline derivatives

Abstract

A new, convenient synthesis of (±)-glaziovine (N-methylcrotsparine)(1) has been devised, involving as the key steps the nitration of (±)-4′-O-benzyl-N-methylcocclaurine (21), followed by catalytic hydrogenation to (±)-8-amino-N-methylcoclaurine (23), diazotization, and irradiation of the o-diazo-oxide (24). The synthesis of (±)-glaziovine by irradiation of (±)-8-bromo-N-methylcolaurine has been reinvestigated and improved. An attempted phenolic coupling reaction of (±)-N-trifluoroacetylcrotsparine (2) by vanadium oxide trichloride resulted in 8-chlorination and 4-hydroxylation [to give compounds (8) and (9)].