A new route to polyoxygenate C and D rings of steroids by oxidation of a Δ8,14-diene steroid with the methyltrioxorhenium–H2O2–urea system

Abstract

In order to find new ways of introducing oxygenated functions in the 15-, 9- and 11-position on steroid rings and at the same time test the reactivity of a conjugated diene steroid toward methyltrioxorhenium (MTO)-catalyzed oxidation with the urea–hydrogen peroxide adduct (UHP), the reactions of 5α-cholesta-8,14-dien-3β-yl acetate 1 with the MTO–UHP system are performed in aprotic solvents. These oxidations are performed both at 0 °C and 25 °C in CHCl₃ or diethyl ether as solvent and in the presence of pyridine ligand. From the reaction of diene 1 in CHCl₃ we isolate two new sterols, 9β-hydroxy-15-oxo-5α-cholest-8(14)-en-3β-yl acetate 3 and 9α,11α,15α-trihydroxy-5α-cholest-8(14)-en-3β-yl acetate 7, while oxidation in Et₂O in the presence of pyridine ligand allows us to isolate the new epoxysteroid 9α,11α-epoxy-15α-hydroxy-5α-cholest-8(14)-en-3β-yl acetate 13. The structure of all new steroids is secured on the basis of chemical evidence and interpretation of spectral data, which include H–H COSY, HMBC and NOESY experiments. These results represent a new and mild method for the functionalization of C and D rings from an 8,14-diene steroid, to give 15-oxygenated sterols, a class of compounds remarkable for their inhibitory action on sterol synthesis in animal cell culture systems.