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 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-orthophenylacethyl-resiniferonol. The meta or para positions of the phenylacetate moiety were substituted with electronegative groups for maximum activity. Compounds exhibiting substituted phenyl propionates at C20 were not irritants in the test used.