Novel Tetrahydrocannabinol Type Compounds

Stoss et al, Chemical Abstracts, vol. 115 (No. 17) p. 183602h (1991). Tetrahedron Letters No. 8, pp. 681-684 (1979) Hendrick et al., Hashish Synthesis of.. . Source Stoss 1993 Reference Stoss 1992 

Photoreaction on (-i-) limonene (orange oil) produces mixed isomers, first couple of fractions canbe used to create active CBl agonists see Schenck 1964. cfs-p-Menth-2-ene-l,8,-diol and mixed isomers from a culture of Penicillium italicum andP digitatum (moldy oranges) see Bowen (1975). 

The main psychotropically active compounds present in Cannabis saliva or in its preparations (marijuana, hashish, etc.) is (3R,4R)-(-)-Al -THC (I). Occasionally small quantities of the compound (3R,4R)-(-)-A6 -THC (II) are found. Both compounds have a pronounced activity on mammals and on humans, producing the typical cannabis effect. This effect can be measured in animals in a quantitative manner by various tests, two of these being the monkey test, Grunfeld et al., Psychopharmacol. 14, 200 (1969) and by the ring test, Pertwee, Brit. J. Pharmacol. 46, 753 (1972). In the monkey test the minimum giving an effect is 50ug./kg of the (3R,4R)-(-)-Al-THC while that of (3R,4R)-(-)-A6 -THC is 0.1 to 0.25 mg/kg. 

In the ring test the above compounds are active at less than 1 mg/kg. There have been prepared various derivatives of the above compounds, having various different side-chains, see Marijuana, 

Chemistry, Pharmacology, Metabolism and Clinical Effects, R. Mechoulam (ed.), Academic Press, New York, 1973. Many of these possess the activity of the natural compounds, frequently at lower dosages and of longer duration, such as in the monkey test, 24 hours instead of 4 hours with the 1 , 2 -(dimethylheptyl) homologue of (3R,4R)-(-)Al-THC (III). The corresponding A6 -THC compound (IV) acts at 0.5 mg/kg for 30 hours. 

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Mechoulam, R. Beuer, A. Hanus, L. Devane, W.A. Fatty Acid Derivatives and Pharmaceutical Compositions Containing Same 1997 US 5,618,955 Mechoulam, R. Lander, N. Dikstein, S. Shalita, B. Novel Tetrahydrocannabinol Type Compounds 1979 US 4,179,517... 

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