Structure-activity relationships in allergic contact dermatitis (I). Studies on the influence of side-chain length with derivatives of primin.

Primin (2-methoxy-6-pentyl-1,4-benzoquinone) is a naturally-occurring strong sensitizer from Primula obconica (Primulacease). To determine the effect of side-chain length on sensitizing potency, 15 analogues with linear side chains from C1 to C15 and 4 C6-analogues with branched side chains were prepared synthetically and devoted to experimental sensitization in guinea pigs. The results showed an increase of the sensitizing capacity with increasing length of the alkyl side chain from C1 to C10, reaching a maximum at C11 and C12. On further elongation, the sensitizing potency decreased beyond C13, reaching values which finally were as low as those of the C1 and C3 derivatives. The results mirror findings which formerly have been obtained with other non-quinonoid compounds like catechols, phenols, hydroquinones and gallates. In the plant kingdom, compounds approximating an "ideal allergen" consisting of a quinonoid ring with a 10 or 11 carbon-membered side chain have been identified only once: 2,3-dimethoxy-geranyl-1,4-benzoquinone, a remarkably strong sensitizer found in Wigandia caracasana (Hydrophyllaceae).