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

ABSTRACT

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.