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.