On the active principles of the spurge family (Euphorbiaceae). IV. Skin irritant and tumor promoting diterpene esters from Euphorbia ingens E.Mey.

The irritant and tumor-promoting principles of the latex of Euphorbia ingens E. Mey have been isolated together with several nonirritant compounds. The Euphorbia factors I1, I5, and I6 are esters of ingenane-type poly-functional diterpene alcohols. Euphorbia factor I1 is characterized as the 3-hexadecanoate of the polyfunctional parent alcohol ingenol and Euphorbia factor I6 as the 3-deca-2.4.6-trienoic acid ester of ingenol. Euphorbia factor I5 is the 16-angelate-3-deca-2.4.6-trienoate of 16-hydroxyingenol. Nonirritant diterpenes of the latex are I2, the ingenol-20-hexadecanoate - an isomer of Euphorbia factor I1 - and I4, the 3.7.12-triacetate-8-nicotinate of the macrocyclic lathyrane-type polyfunctional diterpene alcohol ingol. The diterpene alcohols ingenol and 16-hydroxyingenol are inactive as irritants and tumor promoters of mouse skin. Compared to croton oil factor A1 (TPA), the Euphorbia factor I1 exhibits about 1/10 of the irritant and tumor-promoting activity in mouse skin. I1 shows no reasonable tumorigenic activity. Compared with I1, Eupohorbia factors I5 and I6 are more potent irritants and less potent tumor promoters.