Synthesis of some condensed Hetrocyclic Compounds

1) We have made Improvements in the synthesis and puri¬fication of (-)-trans-delta-8-THC and (-)-trans-delta-9-THC on the procedures already reported 1n the literature.2) We deuterated (-)-trans-delta-8-, (-)-trans-delta-9-and (-)-trans-delta-9,ll-tetrahydrocannabinols at the 2 and 4 aromatic positions.3) We synthesized the 2H labeled analogs of delta-8-THC, delta-9-THCand delta-9, 11-THC with 2H at the 10-a position. Only the first one of these three had been reported previously.4) We synthesized delta-9-d3 with 2H labels in the H-8 and H-10 positions.5) We prepared the pure hydrochloride adduct from delta-8-, delta-9- and delta-9,11-THC’s and determined its structure. Although the adduct was reported previously, its stereochemistry was unassigned. Our tentative assignment in addition to establishing the stereochemistry of this impor¬tant cannabinoid intermediate should be a good contribution to cannabinoid chemistry since this is a common intermediate for the synthesis of these compounds.6) Assignment for these compounds were generally made using high resolution 1H NMR and mass spectrometry to a lesser extent.FUTURE APPLICATIONS FOR THE 2H-LABELED CANNABINOIDS.1) We have established methodology for the specific deuteration of three principal cannabinoid isomers ( delta-8-, delta-9-, and delta-9, 11- THC’s ). These deuterated analogs will be particularly for useful studying the interaction of cannabinoids with membranes using high resolution 1H and 2H as well as solid-state 2H NMR*methods.2) The 2H-labeled cannabinoids can be used to elucidate some of the chemical and stereochemical details of cannabi¬noid metabolism. Such studies will require the use of mass spectrometry methods or a combination of gas chromatograph¬ic and mass spectrometric methods.The above synthetic procedures can be used for the tritiation of cannabinoid analogs which can, in turn, be used to study their metabolism and biotransformation.