On the Chemistry of Resiniferonol, II [1] Preparation and Bioactivities of 15,16-Dihydrosimplexin and Methods for its Tritium Labeling

T. Schäfer3, B. Sorg, C. Karalaib, E. Hecker* Deutsches Krebsforschungszentrum, Division Mechanisms of Tumorigenesis, Research Program 3, Risk Factors of Cancer and Cancer Prevention, Im Neuenheimer Feld 280, D-69009 Heidelberg, Germany Z. Naturforsch. 49b, 128-134 (1994); received September 6,1993 Daphnane Derivatives, Diterpene Esters, Simplexin, Skin Irritant Activity, Skin Tumor Promoting Activity Excoecaria factor 0 1 the daphnane type polyfunctional diterpene ester 5 /S-hydroxy6 a,7 a-epoxyresiniferonol-9,13,14-orf/i0-(2,4,6-decatrienoate) may be obtained in reason­ able amounts from the latex of Excoecaria oppositifolia from South East Asia. 0 1 was par­ tially hydrogenated with H2-Pd/C to yield, by saturation of the three double bonds in the orthoester, and of J 1516 in the diterpene moiety, the new 15,16-dihydro derivative of simple­ xin. The latter is the well known daphnane prototype of polyfunctional diterpene esters occurring in Euphorbiaceae and Thymelaeaceae. 15,16-Dihydrosimplexin (DHS) showed pro­ nounced irritant and tumor promoting activities. By analogous hydrogenation of 0 1 with a mixture of 1H2/3H2 a selectively labeled [3H]DHS was obtained that exhibited a particularly high specific activity of 30 Ci/mmole. Thus it is considered most appropriate for use to study the toxicokinetics and -dynamics of daphnane type diterpene esters. To device an alternative of 3H-labeling of DHS or simplexin (SIM) in position 20 of the diterpene moiety DHS-5-benzoate was oxidized by pyridinium chlorochromate. The resultant 20-aldehyde was reduced by sodium borohydride to reconstitute DHS-5-benzoate and, after deprotection, DHS. This route appears appropriate to prepare similarly [20-3H]DHS as well as [20-3H]SIM using sodium [3H]borohydride.