Hashish. 16. Unsaturated side-chain analogs of .DELTA.8-tetrahydrocannabinol with potent biological activity

Abstract

Two delta8-THC derivatives, 4a and 4b, with functionalized side chains were synthesized. Treatment of (+)-trans-p-mentha-2,8-dien-1-ol with the resorcinal 2b followed by removal of the dithiol group with HgO--BF3-Et2O gave the aldehyde 3b. A Wittig reaction of dimethyl (2-oxoheptyl)phosphate with 3b furnished 4a, which was reduced to 4b. Compounds 4a and 4b showed potent cannabinoid-like activity in mice.

Pharmacophoric Requirements for the Cannabinoid Side Chain. Probing the Cannabinoid Receptor Subsite at C1‘

“…The synthesis was carried out analogous to the preparation of 4a using 13 (0.64 g, 2.64 mmol) and boron tribromide (0.56 mL, 5.81 mmol) in anhydrous CH 2 Cl 2 (66 mL). The reaction was completed in 48 h at −78 °C to 0 °C; yield: 87% (0.49 g); yellow gum; (lit …”

“…This was followed by demethylation under boron tribromide conditions affording resorcinol 4b in 84% yield. Similarly, 3,5-dimethoxybenzaldehyde 12 upon treatment with 1,2-ethanedithiol and boron trifluoride etherate gave thioketal 13 (87% yield) which was converted to the corresponding resorcinol 4c 28 in 87% yield, by demethylation using boron tribromide at 0 °C for 48 h.…”

“…Following a well-established protocol, ,, Friedel−Crafts allylation (Scheme ) of resorcinol derivatives 4a , 4b , and 4c with (+)- cis/ trans-p -mentha-2,8-dien-1-ol catalyzed by p -toluenesulfonic acid afforded cannabidiols 3a , 3b , and 3c in 85%, 43%, and 30% yield, respectively. These intermediates were readily cyclized in the presence of boron trifluoride etherate to give the corresponding tetrahydrocannabinol analogues 2a , 2b , and 2c (Table ) in 79%, 69%, and 50% yield.

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Molecular Targets of the Phytocannabinoids: A Complex Picture

“…Δ 8 -THC also displays psychoactivity and is chemically more stable than Δ 9 -THC [32, 33]. Δ 8 -THC shows moderate partial agonistic effects on CB 1 and CB 2 receptors [34, 35].…”

Pentacyclic steroids. 5. Total synthesis of 4,6.beta.-ethano-3-methoxy-8.alpha.-estra-1,3,5(10)-trien-17.beta.-ol and 4,6.alpha.-ethano-3-methoxyestra-1,3,5(10),8,14-pentaen-17-one

“…Caled for C 13 403 (mol wt 202): C, 77.20; H. 6.98. Found: C, 77.27; H, 6.9. 8-Methoxy-2a,3,4,5-tetrahydro-5-vinyl-5-acenaphthenol (15). A solution of 4.6 g (0.023 mol) of the ketone 14 in tetrahydrofuran (10 mL) and ether (15 mL) was added dropwise under nitrogen over 30 min to a stirred and cooled (NaCl, ice bath) solution of vinylmagnesium bromide prepared from 1.2 g (0.05 mol) of magnesium and 6.4 g (0.06 mol) of vinyl bromide in tetrahydrofuran-ether (10 + 10 mL).…”