SYNTHESIS OF ALKALOID THALACTAMINE AND A NEW SYNTHESIS FOR ALKALOID N-METHYL-6,7-DIMETHOXY-1(2H) ISOQUINOLONE

The alkaloid thalactamine (N‐methyl‐5,6,7‐trimethoxy‐1(2H)isoquinolone) was synthesised in two steps from 4,5,6‐trimethoxyhomophthalic acid (1a). Heating la with DMF/POCI3 at 100° furnished thalactamine‐4‐earhoxylic acid which was easily decarboxylated to give the alkaloid thalactamine. By the same two steps, the alkaloid N‐methyl‐6,7‐dimethoxy‐1(2H)‐isoquinolone is obtained from 4,5‐dimethoxyhomophthalic acid. Synthesis for la from 2‐bromogallic acid trimethyl ether was modified to give excellent yield. 5,6,7‐Trimethoxy and 6,7‐dimethoxyisocoumarin‐4‐carboxylic acid esters were synthesised from the homophthalic acids 1a and b by interacting them with DMF/phosphoryl chloride at 0°, to give corresponding 4‐(N,N‐dimethylaminoformylidene)isochroman‐1,3‐dione derivatives Vla and b and treating their alcoholic solutions with dry hydrogen chloride gas. The isocoumarins were converted into N‐methyl‐1(2H)isoquinolonesby treating them with aqueous methylamine. The isochromandione Vla slowly changed into 3‐chloro‐4‐formyl‐5,6,7‐trimethoxyisocoumarin during the working up of the reaction. Copyright © 1978 Journal of Heterocyclic Chemistry