Stereospecific elimination of deuterium as a method for determining the stereochemistry of a number of metabolites of the tetrahydrocannabinols.
The stereospecific elimination of the 3-deuterium atom from metabolites of [2H]-analogues of delta 1-tetrahydrocannabinol (delta 1-THC), delta 6-THC and delta 7-THC has been investigated as a possible method for determining the stereochemistry of metabolites substituted with hydroxy or acid groups in the terpene ring. Elimination of HCOOTMS was found to involve the 3-hydrogen of the axial but not the equatorial isomer of hexahydrocannabinol-7-oic acid, a metabolite of all three cannabinoids. Similar stereospecific eliminations were observed during the loss of TMSOH from the TMS derivatives of 5 alpha-hydroxy-delta 6-THC, 6 alpha-hydroxy-delta 1-THC and 1 alpha, 2 beta-dihydroxy-delta 1-THC. Loss of TMSOH from 1 alpha, 7- and 1 beta, 7-dihydroxy-HHC involved the 3-hydrogen in both cases but the isomers could be distinguished as their alkane-boronate derivatives; only the derivative of 1 alpha, 7-dihydroxy-HHC lost the boronate ring with stereospecific removal of the 3-hydrogen. The stereochemistry of the four isomers of 1,6-dihydroxy-HHC could not be determined in this way as the [M-TMSOH]+ ions from all four compounds had lost the 3-hydrogen, presumably as the result of 1,6-bond cleavage.
D000818:Animals; D001711:Biotransformation; D003903:Deuterium; D013759:Dronabinol / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007553:Isotope Labeling; D051379:Mice; D008968:Molecular Conformation; D013237:Stereoisomerism
D013759:Dronabinol; D003903:Deuterium