INVESTIGATIONS INTO THE SKIN-IRRITANT PROPERTIES OF RESINIFERONOL ORTHO ESTERS

A series of esters were produced by partial synthesis from 9,13,14-orthophenylacetyl-resiniferonol. These compounds were tested for irritant effects by means of a mouse ear assay. All of the derivatives, including the parent compound, produced short-term inflammation of mice ears within 1-2 h and the effects did not persist for 24 h. This is in contrast to esters of structurally related tigliane diterpenes which produce a longer-term effect on mice ears. Highly potent irritants were synthesized which exhibited irritant doses 50% in the 0.0012-0.00021 nmol range. These esters were all substituted phenylacetates of the C-20 position of 9,13,14-orthophenylacetyl-resiniferonol. The meta or para positions of the phenylacetate moiety were substituted with electronegative groups for maximum activity. Compounds exhibiting substituted phenyl propionates at C-20 were not irritants in the test used. © 1979 Plenum Publishing Corporation.