The widespread use of marijuana as a recreational drug has led to great interest in the organic, medicinal and biochemistry of the constitutents of cannabis sativa. Much of the interest in these compounds has centered around their synthesis, but no general, regioselective synthesis of cannabinoids has been described. The goal of this research is the development of a general synthesis and its application to the preparation of naturally occurring cannabinoids, their metabolites and analogues. This synthesis of cannabinoids is based on the conversion of a tricyclic ketone (R = C5H11) to delta-9-tetrahydrocannabinol (THC, R = C5H11R' = CH3) and its 11-oxygenated metabolites (R = C5H11,R' = CH2OH and CO2H). Kentone (R = H or C5H11) is prepared in good overall yield by reaction of an aryllithium with a derivative of cyclohexenone or a conversion product Beta-pinene. Metabolites of THC oxygenated on the alkyl side chain will be prepared from substituted ketones of general structure. These syntheses lead to racemic products, but the route employing the pinene derivative will be modified to produce the natural enantiomers. This approach will lead to new syntheses of nabilone (R = C9H19) and the ketone (R = C5H11) used in the EMIT analytical procedure.
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