5P-Steroid

The synthetic value of this reaction should be mentioned. Thus, current production of 5p-steroids from As-3(i-ols, readily available and cheap starting materials, requires a preliminary Oppenauer oxidation or fermentation to the A4-3-keto derivative followed by catalytic hydrogenation under alkaline conditions, as direct catalytic hydrogenation with both heterogeneous and homogeneous systems gives only the 5a isomer. 

Another steric factor becomes important when working with bile acids or other A/B cis-(5p)-steroids 14. Despite the fact that the C9 —H bond is the most electronically favored for electrophilic substitution, ring A which is perpendicular to the steroidal plane blocks the access to it. The fluorine, which has to approach with a solvent molecule, attacks the other tertiary sites at C5, Cl 4 and C17.42... 

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... 

While no data on the role of 3a-reduced neuroactive steroids in PTSD or its treatment in panic disorder patients have been pubhshed to date, opposite changes to those seen in major depression have emerged. At baseline, patients with panic disorder had significantly increased concentrations of the positive allosteric modulators 3a,5a-THP and 3a,5P-THP, together with sig-... 

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

It is well known that some functional groups, such as an oxo or a hydroxyl, which are located far from the 4,5-double bond e.g., at Cl 1, Cl7, or C20, may have a marked effect on the stereochemistry of hydrogenation of 3-oxo-A4-steroids. In some cases 5a-ketones are formed predominantly.268 A typical example is the hydrogenation of cortisone acetate (116) over 5% Pd-C in ethyl acetate (eq. 3.78).269 No evidence was obtained for the presence of 5p derivative in the product. 

TABLE 3.18 The Ratio of 5p K Kp to 5a Ketone from Hydrogenation of 3-Oxo-4-ene Steroids over Palladium Catalyst0 ... 

Compared to the hydrogenation to 5P-ketones, the hydrogenation of 3-oxo-A4 steroids to 5a-ketones is much more difficult over usual heterogeneous catalysts, except in the special cases where the presence of oxo groups may favor the formation of 5a compounds as described above. Dauben, Jr. et al. obtained 5a-cholestan-3-one from cholest-4-en-3-one via transformation into 3-ethylenedioxy A5-derivative 117 by exchange dioxolanation, followed by hydrogenation with palladium catalyst to give exclusively 3-ethylenedioxy-5a-cholestane (eq. 3.79).274 The ethylenedioxy compound may be hydrolyzed quantitatively to the 5a-ketone in the presence of acid. 

Babcock and Fieser obtained 3P-methoxy steroids by hydrogenation of methyl 3-oxo-A-91-11 1 -cholenate (5), methyl dehydrolithocholate (6), and 5a-cholestan-3-one (7) over Adams platinum oxide in methanol in the presence of hydrobromic acid (eq. 5.31 ).98 It is noted that the P-methoxy isomers were produced from the ketones of both 5p (5 and 6) and 5a series (7). 

Kitigenin (= (257 )-5(3-Spirostane-l(3,3(3,4p,5P-tetrol (steroidal saponin) Reineckia carnea (Liliaceae) [ bulb, root] cAMP PDE (179)... 

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