Oxidations of 12-Deoxy-, 12-Hydroxy-, 12-Methoxy-, and 12-Hydroxy-13-methoxy-podocarpa-8,11,13-triene Derivatives

Abstract

Methods for the oxidation of the aryl ring of derivatives of podocarpic acid have been examined. Oxidation of methyl 12-hydroxypodocarpa-8,11,13-trien-19-oate (2) with phenyliodonium diacetate in various solvents gives 8β-substituted dienones. An 8β-chloro dienone is formed during oxidation of the phenol (2) with t-butyl hypochlorite. Oxidation of (2) with dimethyldioxiran gives mainly the 7-ketone (13) but also affords the novel ε-lactone (26), while treatment with ruthenium tetraoxide also affords products of benzylic oxidation. Oxidation of methyl podocarpa-8,11,13-trien-19-oate (4) with m-chloroperbenzoic acid affords a B-ring lactone (29) and, unexpectedly, a 6α-chloro 7-ketone (30). The action of cerium(IV) ammonium nitrate on (2) gives nitro derivatives rather than oxidation products. Oxidation of methyl 12-hydroxy-13-methoxypodocarpa-8,11,13-trien-19-oate (22) with m-chloroperbenzoic acid gives a low yield of a 7-oxo derivative (17) while treatment with ozone gives an unusual α,β-unsaturated γ-lactone (31), the hydroxy lactone (33), the unsaturated keto ester (34), and the substituted furan (35). Oxidation of (22) with Fremy"s salt gives products of ring B oxidation. The structure of (31) has been confirmed by X-ray crystallography.