Drugs derived from cannabinoids. Part 8. The synthesis of side-chain analogues of Δ6a,10a-tetrahydrocannabinol

Abstract

The continuation of studies on the synthesis of side-chain analogues of Δ^6a,10a-tetrahydrocannabinol as potential therapeutic agents has led to the syntheses of a possible metabolite 1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyran-3-ylacetic acid (1) and 2-(1-hydroxy-6,6,9-trimethyl-7,8,9,10-tetrahydro-6H-dibenzo[b,d]pyran-3-yl)pent-4-ynioc acid (17c). The Pechmann condensation of ethyl 4-methyl-2-oxocyclo-hexane-1-carboxylate with methyl 3,5-dihydroxyphenylacetate (11), followed by Grignard reaction, was utilized to produce the pyran (1). The key step in the synthesis of the propargylacetic acid (17c) was propargylation of the malonate (15) under phase-transfer catalysis.