Radical relayed remote functuinalization of corticosteroid intermediate

Abstract

Δ9,11-5α-16α, 17α- epoxypregnene-3α-o1-20-one(V), an important intermediate for the preparation of anti-inflammatory agents such as betamethasone, dexamethasone, and triamcinolone, was synthesized from commercially available Δ5-16α, 17α-epoxypregnene-3β-o1-20-one(I) in several steps by utilizing m-iodobenzoate template. The compound(I) was hydrogenated under 50 psi. H_2 pressure in ethanol or isopropanol, then esterified with m-iodobenzoic acid, triphenylphospine and diethyl azodicarboxylate by esterification-inversion method in 80% and 76% yields respectively. m-Iodobenzoate(III) underwent radical relayed remote chlorination under photolysis with 300W sun lamp or reflux condition then directly saponified and dehydrohalogenated by methanolic potassium hydroxide to yield the 9(11)- unsaturated compound(V) in 66% and 60% yields respectively. The compound(V) was then deepoxydated to corresponding enone(VI) and compared to conversion product of Δ9,11-3-epi-tigogenine by Dauben-Fonken method. The spectral data of the intermediate products were analyzed and found them identical with the literature data.