Naftali Lander

Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative

Abstract The individual enantiomers of the 1,1-dimethylheptyl homolog of 7-hydroxy- Δ 6 -tetrahydrocannabinol, (1) and (2a), which exhibit distinct pharmacological profiles, have beenobtained with very high e.e. by synthesis from the antipodes of myrtenol.

Cannabinoids and serotonin uptake by blood platelets: Evidence for multiple sites of action

Abstract The effect of cannabinoids on parameters of 5-hydroxytryptamine (5-HT) uptake by human platelets was examined. Natural and synthetic cannabinoids differing in the pyrene ring of the hydro-phobic side chain or in steric configuration, inhibited differentially the saturation level of 5-HT uptake, the active uptake and the passive transport of the neurotransmitter, indicating multiple sites of action of the drugs. The pattern of inhibition did not correlate with the psychomimetic specificity of the cannabinoids.

The ovulation blocking effect of cannabinoids: structure-activity relationships.

Abstract (1) Δ1-Tetrahydrocannabinol (Δ1-THC), the major psychoactive ingredient of cannabis, prevents ovulation when administered at 14:00 hr to pro-oestrous rats ( ed 50 = 0.98 mg/kg) . Δ6-Tetrahydrocannabinol (Δ6-THC), a psychoactive isomer of Δ1-THC, was a less potent inhibitor of ovulation ( ed 50 = 3.76 mg/kg) . However, the potent psychoactive 5′-(1″,2″ dimethylheptyl) (DMH) homologue of Δ6-THC (Δ6-THC-DMH) had a 60-fold higher ovulation-blocking potency ( ed 50 = 0.064 mg/kg) than the parent compound and about 15 times higher potency than Δ1-THC. Moreover, the action of Δ6-THC-DMH was more prolonged than that of Δ1-THC, being expressed even when the compound was administered at 08:00 hr on the day of pro-oestrus, i.e. 6 hr before the critical period for neural triggering of ovulation. (2) (+) Cannabidiol [(+)CBD] was only weakly active as an ovulation blocker and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl equatorial) (compound 2a) and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl axial) (compound 3a) were inactive, but substitution of a DMH side chain for the amyl side chain of these three compounds resulted in significant enhancement of ovulation-inhibiting activity. (−)CBD and its DMH homologue did not affect ovulation in pro-oestrous rats. (3) (+) CBD-DMH (which showed ovulation inhibiting activity in the rat) has been found to be devoid of psychotropic activity when tested in rhesus monkeys (10 mg/kg). Apparently a separation between psychotropic and hormonal activity in the cannabinoids is possible.

Spectral effects in cyclobutane derivatives : The bathochromic-hypochromic shifts in compounds related to verbenone

Abstract The bathochromic-hypochromic spectral shifts, observed in bicyclic enones that contain a 4- or a 3-membered ring, are discussed in molecular-mechanical and molecular-orbital terms. It is proposed that the effect, not only by the cyclopropane but also by the cyclobutane ring, is due to extension of the CCCO chromophore, and not to its mere distortion from “normal” geometry. The high-energy absorption of umbellulone ( 3 ), 220 nm in ethanol, is characterized as a second π-π * . 2-Methylbicyclo[3.2.1]oct-2-en-4-one ( 7 ) has been synthesized, and its preparation and spectrum are described.