Skin irritants of Euphorbia fortissima

By means of a combination of partition and chromatographic methods six irritant constituents were isolated from the fresh latex of Euphorbia fortissima. Compounds A-D were di-esters of the common parent diterpene 12-deoxyphorbol, and compounds E and F were mono-esters of the same diterpene. The fresh latex had an irritant dose 50% (ID50) on mice of 0-64 mug mul- minus 1. Compounds A-D are short-acting irritants reaching a maximum activity within 4 h of application to the skin, whilst the monoesters maintained potent irritant effects for up to 24 h. Selective hydrolysis of the di-esters at the C-20 primary ester group also produced mono-esters of greater potency after 24 h. An increase in the length of the fatty acid located at C-13 produced greater biological activity in both the mono- and di-ester groups.