Studies on proaporphine and aporphine alkaloids. Part VI. Synthesis of (±)-glaziovine by spiran ring construction on a cyclopent[ij]isoquinoline; stereochemistry of reduced proaporphines

Abstract

The Wittig reaction of methoxymethyltriphenylphosphonium chloride (11) with 2,3,8,8a-tetrahydro-6-hydroxy-5-methoxy-1-methylcyclopent[ij]isoquinolin-7(1H)-one (4), obtained from 1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline-1-acetic acid (6) and polyphosphoric acid, gave the Z-enol ether (17) and, by hydrolysis, the cyclopent[ij]isoquinoline-7-carbaldehyde (19); the latter afforded (±)-11,12-dihydroglaziovine (20), along with a small amount of the 8,9-dihydro-isomer (21), on ring formation with methyl vinyl ketone, catalysed by 1,5-diazabicyclo[5.4.0]undec-5-ene. Bromination of the O-acetate of (20), followed by dehydrobromination, yielded (±)-glaziovine (1). The relative configurations of the asymmetric centres of compounds (20) and (21), as derived from an X-ray crystallographic analysis of the hydrobromide of (20), provide a reference in the stereo-chemistry of reduced proaporphines, such as amuronine (16), to which a revised (6aS,7aS)-configuration has been assigned.