Steroid strong acids

An extensive study of the A" -3-keto steroid system reveals a number of selective exchange reactions. For example, under controlled conditions in the presence of a strong acid catalyst such as deuterium chloride, it is... 

In the early days of steroid chemistry, dehydrations were usually carried out under rather drastic conditions, frequently in the presence of strong acids (see, for example, ref. 176, 181, 182). Such conditions have been replaced by milder and more selective methods, except in those instances when either the product is stable e.g. ref. 183, 184) or rearrangement is desired. The importance of stereochemical factors in rearrangements is widely recognized for instance, the Westphalen rearrangement of 5a-alcohols (92) cf. ref. 185,... 

The sequence (81 84) has been proposed - to account for this process which involves decomposition of the aci-nitro anion by strong acid. The a-carbonyl group presumably stabilizes the aci-salt and thus could be responsible for inhibiting the normal Nef reaction. A similar transformation has been observed in the case of a 16-nitro-17-0X0 steroid. 

Kober reaction of phenolic steroids with strong acids leading to polymethyne ( [18, 19],... 

Silicic acid (silica gel) Strong Steroids, amino acids, lipids... 

When dissolved in superacidic media, complex molecules such as steroids or alkaloids undergo polyprotonation of reasonably distant functions. This prevents the degradation generally observed under usual strong acidic conditions. Moreover, the lack of basic or nucleophilic entities in the medium avoids further processes... 

The hydride transfer reaction catalyzed by strong acids has also been successfully adapted in the natural product chemistry. Jacquesy et al.870 have found that protonated dienones and enones of steroid nucleus can be conveniently reduced in HF—SbF5 medium under hydrogen pressure. The reaction has also been carried out with added hydrocarbons (methylcyclopentane, cyclohexane) as hydride donors.871 The proposed mechanism is depicted in Scheme 5.89. 

There have been known many examples that the hydrogenation of 3p-substituted A5-steroids yields mainly or exclusively saturated steroids of 5a series.166 Lewis and Shoppee studied the influence of various 3 a substituents on the stereochemical course of the hydrogenation of A5-steroids, and found that the 3a substituents lead to the preferential and sometimes exclusive formation of 5P-cholestane derivatives.166 The hydrogenations over platinum oxide were effectuated in methanol or ethyl acetate in the presence of traces of strong acids such as perchloric acid, sulfuric acid or hydrobromic acid. The results summarized by Lewis and Shoppee (eq. 3.34), which also include those by Haworth et al.,167 suggest that the bulkier the axial 3a substituent, the larger is the proportion of 5P steroid formed. The hydrogenation of A4-steroids usually leads to a mixture of 5a and 5P compounds and the stereochemical influence of 3a and 3P substituents is less marked than in the cases of A5-steroids.168... 

ANALGESICS, NON-STEROIDAL ANTIINFLAMMATORY DRUGS, AND OTHER STRONGLY ACIDIC DRUGS... 

In an attempt to identify the chromophoric systems resulting from reactions of steroids with strong acids ( colour reactions Kober, Allen, Oertel, Talbot, Salkowski, and Liebermann-Burchard reactions) a detailed study has been made, with use of all the usual spectroscopic techniques. Visible colours are attributed generally to charge-transfer between the steroid, as donor, and a delocalized carbonium ion, generated from the steroid in acidic media, acting as acceptor. The structures of the steroidal carbonium ions are discussed. 

Oxiranes yield oxazolines with nitriles in the presence of strong acids. The reaction proceeds with inversion, with complete stereospecificity. A new application of the Ritter reaction has been reported the opening of epimeric steroid-16,17-oxiranes in acidic medium with acetonitrile. The reactions of unsaturated hydroxynitriles formed from a-ethylenic oxiranes have been investigated. Numerous publications have appeared on the kinetics of reactions with carboxylic acids and their derivatives. ° ... 

Technically, acid hydrolysis is often preferred (except for acid-labile hormones), because the process offers simplicity and speed and usually results in complete hydrolysis regardless of the nature of conjugates. Enzymatic hydrolysis requires special attention to factors such as optimal concentration and type of enzyme, pH, temperature, and duration of incubation. In addition, the possible presence of enzyme inhibitors, which vary in amount and nature with different specimens, may affect the completeness of hydrolysis. In spite of potential problems, enzymatic hydrolysis is used for plasma analysis of steroids that are labile in strong acid solution (e.g., pregnanetriol and corticosteroids), and because it prevents interference from substances that are produced by acid hydrolysis. Enzymatic hydrolysis, for example, has been used successfully to determme the urine concentration of estrone and the plasma concentration of estrone sulfate in postmenopausal women. 

Enamines [after citation of ref. 4], Gadsby and Leeming43 used eniminium salts for protection of a A4-3-keto grouping of steroids. The enamine (2) is formed as usual from pyrrolidine and treated with a strong acid such as hydrochloric or perchloric acid to form the eniminium salt (3). Various electrophilic reactions at C 7 or... 

Hydrogenolysis to acids occurs also when R is tertiary, in the presence of strong acids or in bromo esters like steroid 1 [equation (f)] . Both reactions proceed via an alkene intermediate. 

The A5 double bond in steroids is relatively inert towards hydrogenation under neutral conditions, but can be activated by addition of acids. The catalytic effect is determined by the strength of the acid. Thus weak acids (pKa > 3) are ineffective, while strong acids (pA < 3) are efficient catalysts16. This allows regioselective hydrogenation of other double bonds which can be reduced under neutral conditions. Over platinum, the A3 double bond is hydrogenated nearly exclusively from the ot-face. The 5/1-product is only formed in the presence of 3a-substituents. 

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