377
X0,ms
A Steroidal Analog of a Tetrahydrocannabinol
Olivctol (IV) was coiidenscd with 10-mcthyl-lcarboniethoxy-t,.a7fs-2-decalone (1‘)‘jin the presence of
It. K. RAZDAN, 13. G. P A R S , F. E. GRANCHELLI, Organic and Medicinal Chemistry Laboratories, .Irlhur D . Little, Inc., Cambridge, Massachusetts 02140 AND
L.S. HARRIS
Department of Pharmacology, University of North Cuiolinu, Chapel Hill, North Carolzna 27516 Eeceived October 20, 1967
‘I’hc recent interest in the active conbtituents of hashish, A1- and A6-3,4-t,.ans-tetrahydrocannabinols prompts u5 to record our findings on related compounds.* Another tetrahydrocannabinol, 11, with the double bond in the 3,4 position and in conjugation with the aromatic ring mas synthesized by both -4dams and Baker3 arid Todd, et aLJ4and was shown to possess a
I11
pharmacological profile similar to I, particularly in its effects on the central nervous system (CXS). We now wish to report the synthesis and biological act’ivity of a steroidal analog (111) of tetrahydrocannabinol IT. This has been achieved by utilizing a different route from that used by Smith et u Z . , ~ to synthesize 6-oxa steroids. Recently Stork and his coworkers6 have shown that alkylation and carbonation of ketones by trapping the enolates from the reduction of a#-unsaturated ketones can give synthetically useful materials, e.g., V. This suggested t’o us an entre6 into oxa steroids of type I11 by Utilizing the Pechmarin condensation and thus allowing one to vary substituents in the aromatic ring, which is otherwise difficult. We had hoped that the steroidal analog I11 would retain the CNS activity possessed by tetrahydrocannabinols I and 11. (1) (a) R . Mechoulam and 1’. Shvo. Tetrahedron, 19, 2073 (1963); (b) T. Gaoni and R. 3Iechoulam, J . B m . Chem. Soc., 86, 1646 (1964): (e) R. Mechoulam and Y . Gaoni. ibid., 87, 3273 (1965): (d) E. C. Taylor, I
