SYNTHESIS OF AN ISOMER OF TETRAHYDROCANNABINOL

Structure of tetrahydrocannabinol derived from natural sources is known except for the position of the isolated alicyclic double bond and the configuration about the 6 0d 10a-carbon atoms. The final resolution of the structure of natural tetrahydrocannabinol depends on the synthesis of the several possible isomers. An attempt to find a method for the preparation of the two pairs of diastereomeric cis- and trans-1-hydroxy-3-n-amyl 6, 6, 9-trimethyl-6a, 7, 10, 10a-tetrahydro-6 dibenzopyrans by a Diels-Alder condensation of isoprene with an appropriately substituted cou marin is reported. Results of the condensation of isoprene with 3-carboxycoumarin, 3-acetylcoumarin, 3-carboxy-5-hydroxy-7-amylcoumarin, and 3-carboxy 5-hydroxy-6-carbethoxy-7-amylcoumarin and the pre paration of trans-1-hydroxy-3-n-amyl-6, 6, 9 trimethyl-6a,7,10,10a-tetrahydro-6-dibenzopyran are described. Trans-1-hydroxy-3-n-amyl-6,6,9 trimethyl-6a,7,10,10a-tetrahydro-6-dibenzopyran is not identical with a tetrahydrocannabinol iso lated from hashish. Work is in progress on the synthesis and optical resolution of the cis- and trans-1-hydroxy-3-n-amyl-6,6,9-trimethyl-6a,7,10, 10a-tetrahydro-6-dibenzopyrans. (Author) Work started Jan 61 and completed Mar 62.