Hashish. I. The structure of cannabidiol.

Cannabidiol, one of the major components of hashish, has been shown to possess structure IIIa. HASHISH (marihuana), the psychotomimetically active resin of the female flowering tops of Cannabis satha L., is one of the most widely used drugs in the illicit market of narcotics in many parts of the world. The chemistry of the constituents of hashish has been the subject of numerous publications since the beginning of this century.2 Due mainly to the masterly investigations2 of Cahn, Adams and Todd, substantial progress has been made in this field. However up till now the structure of only one compound of the cannabis group,namely the physiologically inactive cannabinol (I), has been fully elucidated. We have initiated a program aimed at clarifying some of the remaining problems connected with the chemistry of the constituents of hashish. This paper deals with the structure and stereochemistry of cannabidiol, one of the major components of hashish. Cannabidiol was isolated by Adams3 and Todd4 from marihuana and Indian hemp resin, respectively. Structure II (without stereochemical assignments) was suggested for cannabidiol. hr*d The carbon skeleton and the position of the hydroxyl groups are undoubtly correctly represented by II, for cannabidiol has been convertedsb into cannabinol (I), whose structure has been proved by synthesis,6 The terminal position of the double bond has been adequately proved by chemical means.6c The position of the double bond in the alicyclic ring, 6c however, seemed to require additional corroboration. We now present evidence that cannabidiol in fact possesses structure IIIa. The UV spectral analysis of cannabidiol reported by Adarn&+pd unequivocally shows that the double bond in the terpene ring is conjugated neither to the terminal 1 A portion of this study has been reported at a Meeting of the Israeli Chemical Society, Jerusalem, April 1963 [R. Mechoulam, Bull. Research Council Israel IZA, 57 (1963)]. ’ For reviews on the subject see D. F. Downing, Quart. Rev. 16,133 (1962); A. R. Todd, Experientiu 2, 55 (1946); R. Adams, Harvey Lectures 37, 168 (1942); see also the series of papers by R. Adams, the latest one of which is R. Adams, M. Harfenist and S. Loewe,J. Amer. Chem. Sot. 71,1624 (1949). B R. Adams, M. Hunt and J. H. Clark, J. Amer. Gem. Sot. 62,196 (1940). ’ A. Jacob and A. R. Todd, J. Gem. Sot. 649 (1940). 6 R. Adams and co-workers, J. Amer. Gem. Sot. a 62,2566 (1940); b 62,2402 (1940); c 62,2215 (1940); d 63.2209 (1941); e 62.2194 (1940). a R. Adams, 3. R. Baker and R. B. Wearn, J. Amer. Chem. Sot. 62,2204 (1940); R. Ghosh, A. R. Todd and S. Wilkinson, J. Chem. Sot. 1121, 1393 (1940).