Estrogens by Total Synthesis

The relative simplicity of the structure of estranes compared with those of other classes of steroids has made this structural class an attractive target for work aimed at total synthesis from so-called coal tar starting materials. About half a dozen syntheses have been developed, one of which, the Smith-Torgov synthesis, is probably stiU used commercially. 

The scheme that is likely still used to prepare derivatives of estrone and also some modified estranes on a commercial scale was developed independently by Smith in the USA and Torgov in the former USSR. 

The additional carbon atom required for building the five-membered ring D is then added by means of methyl-magnesium bromide (16-4). The ester at future C15 is reduced to a carbinol by reaction with lithium aluminum hydride. Swern oxidation (dimethyl sulfoxide and oxalyl chloride) next serves to oxidize each of the two resulting hydroxyl groups to carbonyl functions (16-5). Dieckmann-like base-catalyzed condensation then closes the five-membered ring 

Catalytic hydrogenation in this case reduces the extended polyene in a single step to afford estrone 3-methyl ether (13-2) as a single diastereomer. 

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