Studies on the syntheses of heterocyclic compounds. Part 766. A total stereoselective synthesis of emetine and (±)-dihydroprotoemetine

Abstract
Reaction of 3,4-dihydro-6,7-dimethoxy-1 -methylisoquinoline (3) with diethyl αγ-diethoxycarbonylglutaconate (2) in ethanol, followed by silica gel chromatography, formed 3-ethoxycarbonyl-6,7-dihydro-9.10-dimethoxybenzo[a]quinolizin-4-one (6). The same reaction of (3) with (2), followed by reduction with sodium borohydride, afforded 3-ethoxycarbonyl-2-diethoxycarbonylmethyl-1,2,3,6,7,11b-hexahydro-9,10-dimethoxybenzo[a]quinolizin-4-one(10). Condensation of (3) with dimethyl 3-methoxyallylidenemalonate (11) gave 2,3,6,7-tetrahydro-9,10-dimethoxy-3-methoxycarbonyl-2-(ββ-dimethoxyethyl)benzo[a]quinolizin-4-one (13), which was converted to (±)-emetine (1) in seven steps and (±)-dihydroprotoemetine (2) in six steps. Decarboxylation of the enamide form (22) furnished mainly the cis-substituted compound (23).

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