ON THE CHEMISTRY OF RESINIFERONOL .2. PREPARATION AND BIOACTIVITIES OF 15,16-DIHYDROSIMPLEXIN AND METHODS FOR ITS TRITIUM LABELING

Excoecaria factor O1 - the daphnane type polyfunctional diterpene este r 5 beta-hydroxy-6a, 7 yresiniferonol-9,13,14-ortho-(2,4,6-decatrienoa te) - may be obtained in reasonable amounts from the latex of Excoecar ia oppositifolia from South East Asia. O1 was partially hydrogenated w ith H-2-Pd/C to yield, by saturation of the three double bonds in the orthoester, and of triangle(15,16) in the diterpene moiety, the new 15 ,16-dihydro derivative of simplexin. The latter is the well known daph nane prototype of polyfunctional diterpene esters occurring in Euphorb iaceae and Thymelaeaceae, 15,16-Dihydrosimplexin (DHS) showed pronounc ed irritant and tumor promoting activities. By analogous hydrogenation of O1 with a mixture of H-1(2)/H-3(2), a selectively labeled [H-3]DHS was obtained that exhibited a particularly high specific activity of 30 Ci/mmole. Thus it is considered most appropriate for use to study t he toxicokinetics and -dynamics of daphnane type diterpene esters. To device an alternative of H-3-labeling of DHS or simplexin (SIM) in pos ition 20 of the diterpene moiety DHS-5-benzoate was oxidized by pyridi nium chlorochromate. The resultant 20-aldehyde was reduced by sodium b orohydride to reconstitute DHS-5-benzoate and, after deprotection, DHS . This route appears appropriate to prepare similarly [20-H-3]DHS as w ell as [20-H-3]SIM using sodium [3H]borohydride.