Synthesis of the alkaloids escholamine and takatonine via a modified pomeranz–fritsch reaction

Abstract

Treatment of the Schiff's base formed from piperonal and aminoacetaldehyde dimethyl acetal with benzylmagnesium chloride gave 1-(3,4-methylenedioxyphenyl)-2-phenylethylaminoacetaldehyde dimethyl acetal (4; R¹= R²= H), the tosylate of which was cyclised under acidic conditions to 1-benzyl-1,2-dihydro-6,7-methylenedioxy-2-tosyliquinoline (5; R = H) and trans-3,4-methylenedioxystilbene (6). Further acid treatment of (5; R = H) gave 1-benzyl-6,7-methylenedioxyisoquinoline (7; R = H) and 6,7-methylenedioxyisoquinoline. Similar results were obtained using p-methoxybenzylmagnesium chloride with the same Schiff's base (from piperonal). 6,7-Methylenedioxy-1-(3,4-methylenedioxybenzyl)isoquinoline (10)(escholamine free base) was prepared from 6,7-methylenedioxyisoquinoline and 3,4-methylenedioxybenzyl chloride via a Reissert compound in 60% yield. Similarly 5,6,7-trimethoxyisoquinoline and p-methoxybenzyl chloride gave 5,6,7-trimethoxy-1-(4-methoxybenzyl)isoquinoline (11)(takatonine free base) in 75% yield.