Tetrahydrocannabinol yield

The reaction of dehydrolinalool acetate (274) with the homocuprate of olivetol bis(tetrahydropyranyl ether) (273) was expected to yield cannabichromene by analogy with the reaction with 3-acetoxy-3-methylbut-l-yne (79JCS(Pl)20l). However, the major product was 3,4-m-A1,2-tetrahydrocannabinol (275), which could readily be purified, thereby providing a valuable route to this substance. Its formation is thought to involve the generation of an allene which proceeds to the chroman via an allylic cation and trans addition to the isopropylidene group (Scheme 69). 

Resorcinols. Condensation of this diene with the ketal of a fi- keto acid derivative results in a resorcinol with complete regiocontrol. Thus, the TiCl4-catalyzed reaction of 1 with ketal ester 2 results in the resorcinol 3 in 72% yield. However, use of the acid chloride 4 corresponding to 2 in the same reaction results in the isomeric resorcinol, methyl olivetolate (5). The regiocontrol is based on the reactiv ity order acid chloride > ketal > ester. The resorcinol 5 was used in a biomimetic synthesis of the chromene A1 -tetrahydrocannabinol (6), a component of marijuana. 

Fellermeier, M. and Zenk, M.H. (1998) Prenylation of olivetolateby a hemp transferase yields cannabigerolic acid, the precursor of tetrahydrocannabinol. FEES Lett., 427, 283-85. 

Deuteration and trittation.7 Labeled trifluoroacetic acid has some advantages for deuteration and tritiation. It is obtained in quantitative yield by mixing trifluoroacetic acid and labeled water. It has excellent solvent properties and also functions as the acid catalyst. The uptake of label can be followed by nuclear magnetic resonance the reagent is readily removed by evaporation in vacuo. In the case of olefins, addition to form the trifluoroacetate occurs simultaneously. It lias been used for the labeling of A8- and A9-tetrahydrocannabinol. 

Hallucinogenic agents - Several investigators reported the identification and synthesis of active metabolites of (A )-tetrahydrocannabinol (THC). Incubation of the latter with preparations of rat or rabbit liver, yielded 7(ll)-hydroxy-A (A )-THC. Another report described the synthesis of 7-hydroxy-A W THC, an active metabolite, originally isolated from the urine of rabbits . 

A simple one-step synthesis of (-)-A -tetrahydrocannabinol from chrysanthenol and olevitol has been reported. The anodic oxidation of the enol acetate of iso-pinocamphone (613), obtained in three steps by standard methods from l-oc-pinene, provides a novel synthesis of /-carvone (614 34% overall) in essentially quantitative optical yield. The choice of solvent (CH2CI2-ACOH) and supporting electrolyte (Et4NOTs) is important. Treatment of a-pinene with Bu OK/Bu"Li gave (615) which... 

Significant advances in the chemistry of the cannabinoids have been made in recent years and several syntheses were reported in 1967. Of particular interest was the elegant method of Mechouiam t al.1 involving condensation of (—)-verbenol with olivetol to give the psychoactive (—)-a1(°) -3,4-trans-tetrahydrocannabinol (THC)(31) which in turn was converted to (-)-A THC( ) the overall yield of 32 was 21%. Using a similar approach. 

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