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Addition and elimination of HCl to tetrahydrocannabinol isomers. A method for the preparation of stereospecifically 2 H‐labeled cannabinoids
Author(s) -
Banijamali Ali R.,
Van Der Schyf Cornelis J.,
Makriyannis Alexandros
Publication year - 1998
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/(sici)1099-1344(199802)41:2<121::aid-jlcr55>3.0.co;2-s
Subject(s) - chemistry , protonation , double bond , tetrahydrocannabinol , stereochemistry , hydrogen chloride , medicinal chemistry , stereospecificity , cannabinoid , organic chemistry , ion , catalysis , biochemistry , receptor
Addition of HCl gas to (−)Δ 8 ‐, (−)Δ 9 ‐, or (−)Δ 9,11 ‐THC solutions at −60°C results in the formation of 9α‐ and 9β‐chlorohexahydrocannabinol (Cl‐HHC). The addition appears to involve initial protonation of the double bond in the form of a bridged hydrogen cation followed by attack of the chloride anion at the most substituted 9‐position. For both steps in the addition reaction the stereochemistry is dependent on the double bond position in the THC isomer. Elimination of HCl from each of the two addition products using potassium‐ tert ‐amylate leads exclusively to Δ 9 ‐THC in the case of 9β‐Cl‐HHC and to Δ 9,11 ‐THC in the case of 9α‐Cl‐HHC. The individual addition products can be separated and used to obtain regio‐ and stereochemically 2 H‐isotopically labeled tetrahydrocannabinols which can be used in biophysical and biochemical studies. © 1998 John Wiley & Sons, Ltd.