14/3-Hydroxy steroids

The preparation of estranes via 19-hydroxy steroids has also been accompHshed microbially. 19-Hydroxycholesterol, prepared chemically (39), is incubated with JS icardia restrictus to provide estrone (20) direcdy (44). Similarly, 19-hydroxyandrost-4-en-3,17-dione is converted to estrone (20) (45). 

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

The 3-bromotetrahydropyranyl ether was prepared from a 17-hydroxy steroid and 2,3-dibromopyran (pyridine, benzene, 20°, 24 h) it was cleaved by zinc/ethanol. ... 

The tetrahydrothiopyranyl ether was prepared from a 3-hydroxy steroid and dihy-drothiopyran (CF3COOH, CHCI3, 35% yield) it can be cleaved under neutral conditions (AgN03, aq. acetone, 85% yield). ... 

A good example is the reduction of 11-keto steroids (69) which gives only the llJ -hydroxy derivatives (70) with metal deuterides. Generally, the 1 la-alcohols are obtained in good yield by reduction with lithium in liquid ammonia-methanol mixtures. By analogy, llj -dj-lla-alcohols (71) are expected when a deuterioammonia-methanol-OD system is used. (For an alternate preparation of an 11/5-dj-l la-hydroxy steroid, see section III-C). 

During the course of a mass spectrometric study of D-homo-14-hydroxy steroids, it was necessary to prepare the corresponding C-8 deuterium labeled analogs. The preparation of these uncommon steroid derivatives has been achieved by repeating the Torgov total synthesis [(257) (262)] with a deuterium-labeled bicyclic starting material (258). Both of the resulting 14-hydroxy epimers, (261) and (262), exhibited better than 90% isotopic purity. ... 

A 8 A solution of chromic acid is prepared by dissolving 26.72 g of chromium trioxide in a mixture of 23 ml of concentrated sulfuric acid and enough water to make the total volume of the solution 100 ml. Rapid dropwise addition of a slight excess of this reagent to an acetone solution (2 % or less) of the hydroxy steroid at room temperature or below with stirring usually results in complete conversion to ketone in less than 10 min. The product is isolated by dilution with water followed by filtration or extraction. 

Oxidation of 20-keto-21-hydroxy steroids with oxygen in aqueous methanol or in anhydrous methanol in the presence of cupric acetate has been reported to give good yields of the corresponding 21-aldehydes. 

SELECTIVE OXIDATIONS OF HYDROXY STEROIDS / 241 VIII. SILVER SALTS... 

If homolytic reaction conditions (heat and nonpolar solvents) can be avoided and if the reaction is conducted in the presence of a weak base, lead tetraacetate is an efficient oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones. The yield of product is in many cases better than that obtained by oxidation with chromium trioxide. The reaction in pyridine is moderately slow the intial red pyridine complex turns to a yellow solution as the reaction progresses, the color change thus serving as an indicator. The method is surprisingly mild and free of side reactions. Thus 17a-ethinyl-17jS-hydroxy steroids are not attacked and 5a-hydroxy-3-ket-ones are not dehydrated. 

A solution of bismuth trioxide in hot glacial acetic acid provides a specific method for the oxidation of acyloins. " The reaction rate is dependent on the steric accessibility of the ketol system. A 2,3-ketol requires less than one hour for completion but an 11,12-ketol is not yet fully oxidized in thirty hours." The reaction is highly selective as a-keto acids, hydrazines and phenols are not oxidized. In a direct comparison with cupric acetate, this procedure is somewhat superior for the preparation of a 2,3-diketone from a 2-keto-3-hydroxy steroid. ... 

Extension of this reaction to other substrates, however, revealed that it is more complex, and that side products are formed depending on (1) the nature of the substrate, (2) the reaction conditions, e.g. temperature and solvent,and (3) the method of work-up." Thus, in addition to the desired substitution products, primary and secondary hydroxy steroids generally yield esters and ethers and undergo simple dehydration as well as dehydration accompanied by rearrangement. 

Interesting results are obtained with the 19-hydroxy steroids (12) and (15). 19-Hydroxyandrost-4-ene-3,17-dione (12), when refluxed with the fluoro-... 

Reaction of Hydroxy Steroids with Diethyl(2-chloro- h h2-trifluoroethyl)amine... 

Fluorination of hydroxy steroids with diethyl (2-chlor o-1,1,2-trifluoroethyl) amine... 

A variety of conditions has been used to prepare oxiranes from trans-hxomo-hydrins. In general, bromohydrins are heated in a solution of 5-10% methanolic potassium hydroxide for 30 min to 8 hr. Longer reflux times are required for bromohydrins which are not anti-coplanar, e.g., diequatorial bromohydrins. A 5 % solution of potassium acetate in boiling ethanol can be used to cyclize steroidal bromohydrins containing base sensitive groups. The use of 1.1 equivalents of sodium methoxide per equivalent of steroid in methanol solution is especially recommended for 9a-bromo-l lj5-hydroxy steroids. 

The action of methylmagnesium iodide on 3-pyrrolidino-A -4-ketones (19) gives the 4a-methyl-4l -hydroxy steroids (20). ... 

High vacuum sublimation of the 3-monobenzoate of (32) or tosylchloride dehydration gives 3/ -benzoyloxy-7-methylenecholest-5-ene (33). The configuration of (32) is probably as shown since 7a-hydroxy steroids dehydrate readily to yield homoannular dienes. In an analogous reaction ethyl and iso-butyl Grignard reagents give alkylidene compounds as the only isolated products. 

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