摘要:

20 CHEMICAL COMMUNICATIONS Cannabichromene, a New Active Principle in Hashish1 By Y . GAONI and R. MECHOULAM (Institute of Organic Chemistry, Weizmann Institute of Science, Rehovoth, Israel) IT is generally assumed that the active principles of hashish are double bond or stereochemical isomers of tetrahydrocannabinol.2 Recently we were indeed able to isolate, elucidate the structure of, and synthesize the active A1-tetrahydrocanna- binol (I).3 However we have been unable to detect the presence of any additional tetrahydro- cannabinols in ha~hish.~ We now report the isolation of a second active constituent which is of a different structural type. For this new component we suggest the name cannabichromene and assign structure (11). Chromatography of a hexane extract of hashish on Florisil yielded the following identified com- pounds (in order of increasing polarity) : canna- bidiol,5 Al-tetrahydr~cannabinol,~ cannabinol, cannabichromene (1.5% of the total extract) and cannabigerol.6 The fractions containing canna- bichromene were re-chromatographed twice and distilled.Purity was established by thin-layer chromatography. Cannabichromene (11), C21H3002, Xmax(Et0H) 228, 280 mp ( E , 25.100, 8900) ; [aID(CHCl3) - 9" ; mol. weight (mass spectrum) 314; two double bonds] gives a crystal- line 3,5-dinitrophenylurethane [m.p. 106-107° ; [a],(CHCl,) - 1.5"]. The ultraviolet spectrum of (11) indicates conjugation of one of the double bonds with the ring and is compatible with the spectra of similar chromenes derived from re- sorcinol derivatives.' The n.m.r.spectrum indi- cates that ( a ) the two aromatic protons are magnetic- ally nonequivalent (8, 5.97, 6.15) and that one of the methyl groups on the terpene moiety is a to an oxygen atom (6, 1.32 singlet), thus determining the point of attachment of the ether-oxygen atom, the other oxygen atom being in a free phenolic group ; (b) two of the olefinic protons are not flanked by any hydrogen atoms (sharp AB pattern; 6, 5-44, 6.60; JAB, 10 c./sec.) ; (c) the second double bond is in an isopropylidene grouping (two methyl groups, 6, 1.58, 1.62; one olefinic proton; 6, 5.05). The findings are compatible only with structure (11). Corroboration of structure (11) was obtained by catalytic hydrogenation of cannabichromene to ( - )-tetrahydrocannabichromene (111) [Amax (EtOH) 281, 275 mp (6, 1250, 1230); [aID(CHC1,) -2-3"; 8, 1.20 (methyl group a to an oxygen atom), 5-98, 6- 10 (two nonequivalent aromatic protons), no olefinic protons or olefinic methyl groups; 3.5- dinitrophenylurethane of (111), m.p.125-128'1. ( f )-Tetrahydrocannabichromene (111) was syn- thesized as follows: cannabigeroP (IV) on boilingNUMBER 1, 1966 with toluene-p-sulphonic acid in benzene gave (V) , which is isomeric with the starting material. The chromane (V) [a, 1.25 (one methyl group a to an oxygen atom), 1-60, 1.65 (two olefinic methyl groups), 6.00, 6.12 (two nonequivalent aromatic protons) ] on catalytic hydrogenation yielded (f)-(111) (3,5-dinitrophenylurethane, m.p. 125- 128’). The n.m.r., ultraviolet, and infrared spectra of (A)-(111) and (-)-(111) are identical.21 In Nature cannabichromene is probably formed from cannabigerol (IV) through 8-hydroxycanna- bigerol (VII) . This hypothetical biogenetic inter- mediate has been postulated by us3b in the forma- tion of cannabidiol and A1-tetrahydrocannabinol (I) via a different cyclisation path. When administered to a dog cannabichromene caused sedation and ataxia. (IV) 1 biosynthesis (OH w5H11 OH (Received, November 23rd, 1965; Corn. 732.) 1 Hashish, Part VIII. 2 Inter alia, (a) F. Korte and H. Sieper in “Hashish, Its Chemistry and Pharmacology,” Ciba Foundation Study Group, No. 21, Churchill, London, 1965, p. 15; (b) L. S. Goodman and A. Gilman, New York, 1955, p. 171; (c) A. R. Todd, Experientia, 1946, 2, 55. 3 (a) Y. Gaoni, and R. Mechoulam, J . Amer. Chem. Soc., 1964,86,1646; (b) R. Mechoulam, and Y. Gaoni, J . Amer. Chem. Soc., 1965, 87, 3273. 4 In view of the easy conversion of A’-tetrahydrocannabinol into the A1(s)-isomerl the presence of the latter in hashish should be expected. 5 R. Mechoulam and Y. Shvo, Tetrahedron, 1963, 19, 2073. Y. Gaoni, and R. Mechoulam, Proc. Chem. SOL, 1964, 82. 7 H. Fukami, M. Nakayama, and M. Nakajima, Agric. and B i d . Chem. (Japan), 1961, 25, 247; R. Ghosh, A. R. For Part VII see: Y. Gaoni and R. Mechoulam, Tetrahedron, in the press. In our samples however i t is absent. Todd, and S. Wilkinson, J . Chem. Soc., 1940, 1124; H. Asahina, Bull. Narcotics, 1957, 9 (No. 4), 17.

ISSN:0009-241X    

DOI:10.1039/C19660000020

出版商:RSC    

年代:1966

数据来源: RSC