Semi-Syntheses of Estrone

An inherent problem in the transformation of plant steroids to nor-steroids (compounds lacking the C g methyl group) is the removal of the unactivated 19-methyl group and the formation of the required aromatic ring since this was always an absent stuctural feature in those natural product. Early work was concerned with the use of diosgenin (ref. 108) and the derivation of a dienone ring (ref. 109) which was then thermally aromatised (ref, 110). 

Subsequently readily available cholesterol has been degraded microbiologically to androst-1,4-diene-3,17-dione which is then ketalised with ethanediol to form regiospecifaically the 3-ketal, aromatisation of which occurs upon mild reaction with lithium in THF containing diphenyl/diphenylmethane Reaction takes place by way of the radical anion obtained from the lihium and diphenyl and diphenylmethane quenches the methyllithium arising from the leaving angular 

Thermal aromatisation has been applied to the androst-1,4-diene-3,17-dione to obtain estrone, as in the early diosgenin work, namely through the Inhoffen approach, by passage of the dienone in mineral oil through a hot tube at 560°C. 

Reagents (i) Ethane diol, 4-TSA, (ii) Li,biphenyl, THFreflux,(Ph)2CH2 H3O  

The microbial conversion of 19-hydroxycholesterol, obtained chemically in three steps from cholestery acetate, to estrone by incubation with the microorganism CSD-10 afforded estrone in a single step in 72% yield (ref. 112) following 

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