Synthesis of the alkaloid thalactamine and a new synthesis for the 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.