Syntheses of 11-hydroxy steroids

Syntheses of 11-Hydroxy Steroids. These syntheses include the preparation of cortisone, aldosterone, and the tricyclic intermediates corresponding to them. In all such syntheses, ring D was added to tricyclic C14-ketones also having oxygen substituents in positions C3 and Cii. The methods of obtaining these intermediates can be divided into two 

Isomers of ketone (67) have also been obtained, opening up the route to the synthesis of isomers of cortisone. The oxidation of (67) yielded the anti-trans-diketone (71) and its reduction the corresponding diol (70). The anti-c is-diketone (72) was obtained from the diol (64) by acelyl protection of the 14-hydroxy group, oxidation at C, deacelylation to the ketol (68), and oxidation of the latter at 0 4. By isomerizing compound (72), the anti-trans-diketone (71) was obtained. By isomerization at Cg and oxidation, the ketol (68) gave a third isomer, the syn-trans-diketone (69) [659]. An unsuccessful attempt has been made to obtain the last of the theoretically possible isomers, the syn-cis compound, by means of a diene synthesis [660]. 

Without the formation of an ethylene ketal protective grouping, the diol (70) was resolved into its optical isomers by crystallizing the brucine salts of the 14-hemisuccinates [661] or the strychnine salts of the 14-hemi- 

Another method of synthesis [673-675] differs from the preceding one by the preparation of the BC fragment (91), which was effected by the acylation, hydrogenolysis, and cyclization of the dimethyl ether of hydro- 

Reduction of the A -bond in compound (lOl) with alkali metals and alcohols formed the C14 center of asymmetry. It was found that the stereochemistry of this reaction depends fundamentally both on the reagents used and on the substituent at Cn. Thus, on reduction, lljS -hydroxy derivatives form only the 14/3 -epimers while 11-ketones form mixtures of the two possible epimers. The best results were achieved by the preliminary reduction of (101) to the corresponding llck -hydroxy derivative and the reaction of the latter with potassium and isopropanol in liquid ammonia. This led exclusively to the desired 14o -epimer (100) [93, 685-689]. 

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