Analogues of poison ivy urushiol. Synthesis and biological activity of disubstituted n-alkylbenzenes.

The total synthesis of different isomers and analogues of poison ivy urushiol is described. These include the positional isomers 1-5 and the nitrogen-containing analogues 6 and 8 and their mesylamino derivatives 7 and 9. 3,4-Dimethoxybenzaldehyde, m-dimethoxybenzene, resorcinol, and p-dimethoxybenzene were used as starting materials for compounds 1, 2, 3, and 4, respectively. Compound 5 is prepared by catalytic hydrogenation of bilobol isolated from Ginkgo biloba. Compounds 6 and 7 were prepared from anacardic acid as the starting material while compounds 8 and 9 were prepared from phenol as the starting material. Compounds 1-9 were tested for their ability to cross-react with poison ivy urushiol in sensitized guinea pigs. Compounds 6 and 8 were reactive at the 10-microgram dose level when applied topically, while compound 1 was a skin irritant at that dose. On the other hand, compounds 2-5, 7, and 9 showed no cross-reactivity up to the 30-micrograms dose level. Structural requirements for cross allergenicity are discussed.

1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil. A highly selective antiherpes simplex agent.

The protected nucleoside 1-(2-deoxy-2-fluoro-3,5-di-O-benzoyl-beta-D-arabinofuranosyl)-5-ethylura cil (10) was prepared by condensation of 3,5-dibenzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (9) with 2,4-bis-O-(trimethylsilyl)-5-ethyluracil (8). The ratio in this coupling reaction has been raised to 17:1 in favor of the desired beta-anomer. Deprotection by aminolysis gave 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-ethyluracil (FEAU, 1) in 67% isolated yield from the bromo sugar 9. In vitro data show that FEAU has activity against herpes simplex virus types 1 and 2 comparable to that of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU, 2), 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU, 3), and acyclovir (ACV, 12). The cellular toxicity of FEAU was found to be much lower than that of the other nucleoside analogues. Biochemical experiments indicate that FEAU has similar affinity toward thymidine kinases encoded by HSV 1 and 2 and a much lower affinity for cellular thymidine kinase than thymidine. The in vivo antiviral effects of FEAU, FMAU, FIAU, and ACV were evaluated against herpes infection in a systemic mouse encephalitis model and a cutaneous guinea pig model. While FEAU showed activity comparable to that of ACV in the systemic infection model, it was superior in the cutaneous herpes infection model.

Synthesis and antiallergenic properties of 3-n-pentadecyl- and 3-n-heptadecylcatechol esters.

A synthetic procedure is described for the preparation of 3-n-pentadecyl- and 3-n-heptadecylcatechols and their acetate and alaninate esters. The Wittig reagent prepared from 2,3-dimethoxybenzyltriphenylphosphonium bromide (III) was coupled with 1-tetradecanal or 1-hexadecanal to give the olefins IV and V, respectively. Catalytic reduction of IV and V followed by demethylation with boron tribromide afforded VIII and IX. The acetates were prepared using acetic anhydride and pyridine, while the alaninates were prepared using N-(tert-butoxycarbonyl)-L-alanine and dicyclohexylcarbodiimide followed by removal of the tert-butoxycarbonyl group with hydrogen chloride gas. The esters were active in guinea pigs in the production of tolerance and desensitization or hyposensitization to poison ivy-type contact dermatitis.

Cannabinoids in glaucoma II: the effect of different cannabinoids on intraocular pressure of the rabbit.

Thirty-two different cannabinoids were tested for their ability to reduce intraocular pressure (IOP) in the rabbit. These included many of delta 9- and delta 8-THC derivatives and metabolites along with other natural and synthetic cannabinoids. In addition, some non-cannabinoid constituents of Cannabis were screened using the same model. All compounds were administered intravenously, while only a few were tested topically in mineral oil. Water soluble derivatives of delta 9- and delta 8-THC were prepared and tested topically in aqueous solution. The data revealed that certain derivatives of delta 9-and delta 8-THC were more active in lowering IOP than the parent cannabinoids. In addition, compounds other than delta 9- and delta 8-THC and their derivatives were shown to have activity.