Synthesis of alpha-methylene-gamma-butyrolactones: a structure-activity relationship study of their allergenic power.

Thirty-five alpha-methylene-gamma-butyrolactones have been prepared and their allergenic properties tested on the skin of guinea pigs experimentally sensitized to (a) alantolactone (1), (b) isoalantolactone (2), and (c) alpha-methylene-gamma-butyrolactone (3). The two first groups of animals cross-react to lactones containing 9 to 18 carbon atoms but not to smaller alpha-methylene-gamma-butyrolactones. Conversely, animals sensitized to alpha-methylene-gamma-butyrolactone react only with alpha-methylene-gamma-butyrolactones containing 6 and 7 carbon atoms. These results are discussed in relation with the allergic contact dermatitis mechanism.

Allergenic alpha-methylene-gamma-butyrolactones. Stereospecific syntheses of (+)- and (-)-gamma-methyl-alpha-methylene-gamma-butyrolactones. A study of the specificity of (+) and (-) enantiomers in inducing allergic contact dermatitis.

The enantiomers of gamma-methyl-alpha-methylene-gamma-butyrolactone have been prepared stereospecifically from (R)- and (S)-glutamic acid. Three groups of guinea pigs have been sensitized (Feund complete adjuvant technique) to the (+) isomer, the (-) isomer, and the (+/-) mixture. The animals have been tested with each of the enantiomers and with a mixture of the compounds. Only the (-) enantiomer showed some specificity: guinea pigs sensitized to this enantiomer react weakly to the other compound; in turn, animals sensitized to the (+) enantiomer react similarly to both antipodes. Interestingly, reaction to the (+/-) mixture in each group of guinea pigs was the sum of skin responses to the individual enantiomer. These results should be contrasted with sensitization to (+)- and (-)-frullanolides, sesquiterpene lactones for which strong stereospecificity was observed.