SYNTHETIC APPROACHES TO THE NAPHTHYL-ISOQUINOLINE ALKALOIDS .2. THE TOTAL SYNTHESIS OF (-)-O-METHYLANCISTROCLADINE AND (+)-O-METHYLHAMATINE AND THEIR ENANTIOMERS

An asymmetric total synthesis of the naphthyl-isoquinoline alkaloids (-)-O-methylancistrocladine 39 is described; the synthetic method also provides routes to the atropisomer (+)-O-methylhamatine 43 and the enantiomers of these alkaloids. The asymmetric construction of the biaryl linkage involved the reaction of the Grignard reagent derived from 2-(2-bromo-3,5-dimethoxyphenyl)-1,3-dioxane 7 with (+)-(4S,5S)-4-(methoxymethyl)-5-phenyl-2-(1,4,5-trimethoxy-2-naphthyl)-4,5-dihydrooxazole 5.