Tris-oxygenated pregnanes

Many of the reactions already discussed for the preparation of bis-oxygenated pregnanes can also be used for the synthesis of 17,20,21-tris-oxygenated pregnanes by proper choice of substrate. Thus, reaction of a 17-vinyl-17-hydroxy steroid or a A -21-hydroxypregnene with osmium tetroxide will give the 17,20,21-triol, and the Stork reaction can be applied to 17a-hydroxy-20-keto steroids. 

One reaction touched upon briefly in an earlier discussion is the hydroxyla-tion of a A -20-cyano steroid with osmium tetroxide. When a 21-acetoxyl group is also present, the important dihydroxyacetone side-chain is obtained  

The requisite starting cyanohydrin is readily prepared from a 20-keto-pregnane substitution at C-21 has no effect on the success of this step. However, the stability of the cyanohydrin is markedly dependent on other features of the molecule thus a 3-acetate confers greater stability than the free alcohol, and a 3-ketone is so unstable that subsequent dehydration with phosphorus oxychloride gives poor yields of the A -unsaturated nitrile. 

3-Hydroxy-20-cyanohydrins can be oxidized to 3-ketones in good yield with chromic acid, and the osmate ester of the unsaturated nitrile is also stable to this oxidant. After hydrolysis of the osmate ester, the new 17-hydroxy-20-cyanohydrin which is presumably formed cannot be isolated, but loses hydrogen cyanide during the hydrolysis, and only the 17a-hydroxy-20-ketone is obtained. 

Because the unsaturated nitrile does not react with osmium tetroxide as rapidly as a simple A holefin, selectivity between other unsaturated centers is difficult to achieve. 

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