Cryptic and Free Skin Irritants of the Daphnane and Tigliane Types in Latex of Excoecaria agallocha ¹

Abstract

In the extremely skin irritant and caustic latex of Excoecaria agallocha the major part of the polyfunctional diterpene esters (DTE) (group I) are aliphatic polyunsaturated 9,13,14-orthoesters of the daphnane-type parent alcohol 5β-hydroxyresiniferonol-6α,7α-epoxide, esterified simultaneously in their 20-positions with aliphatic saturated homologous n-carboxylic acids (even numbered, C₂₂-C₃₀). The minor part of DTE is composed of analogous structures of 5β,12β-dihydroxyresiniferonol-6α,7α-epoxide (group II) and of aliphatic 13-polyunsaturated, 20-saturated diesters of the tigliane-type parent alcohol 12-deoxyphorbol (group III). All three groups of DTE exhibit practically no irritant activity on the mouse ear. By alkaline transesterification of groups I-III, the corresponding highly irritant multicomponent mixtures of Excoecaria factors A (OH-20 deacylated) are released. They comprise a mixture of the known Excoecaria factors A1/A2/A3 and three mixtures of hitherto unknown Excoecaria factors A4/A5, A6/A7 and A8/A9. The groups I-III are typical structures of “cryptic irritants”. By an alternative, extremely mild separation procedure the highly irritant mixture A1/A2/A3 was obtained directly. It represents the “free” Excoecaria factors, the natural constituents of the latex responsible for its bioactivity.

Key words

Daphnane-type orthoesters - 12-deoxyphorbol esters - Euphorbiaceae - Excoecaria agallocha - skin irritants