Steroids backbone rearrangement

By analogy with what has gone before, you might now expect a tame hydration or reduction of this cation. Nothing of the sort A rearrangement occurs in which five consecutive 1,2-shifts are followed by an elimination. Since this reaction organizes the backbone of the steroids, it is often called the steroid backbone rearrangement. 

Complex rearrangements involving both the steroid backbone and the cholestane side chain were observed when either the Westphalen diacetate (252) or 5a-cholestane-2a,5-diol (253) was treated with HF at —60 °C. The 25-fluoro-product (254) was isolated in low yield from the 2,5-diol, and an analogous product resulted from the Westphalen diacetate. Inversion of the configuration at C-20 to give the unnatural (20S)-isomer is thought to involve stereospecific hydride transfer from C-25 to a C-20 carbocation subsequent nucleophilic attack at C-25 gives the 25-fluoro-compound. A hydride transfer from C-20 to C-13 is postulated to account for... 

Snatzke [102] has shown that the 3,5,6-triacetate (10), though resistent to mild reaction conditions, can be forced to react via a C<5>-carbonium ion species by heating in acetic anhydride containing an acidic catalyst. A major product, apart from Westphalen s diacetate , was another olefinic compound identified by Blunt, Hartshorn and Kirk [103] as the A 2h7) olefin (ii) resulting from a backbone rearrangement of the steroid skeleton cf. p. 292). 

The study of backbone rearrangements continues unabated (pp. 299—304), some novel routes to D-homosteroids have been explored, and there are several reports of partial aromatizations in steroids (pp. 307—311). 

A survey has appeared of the differences between in vivo and in vitro backbone rearrangements in the polycyclic systems related to steroids and triterpenoids. 

Contraction and Expansion of Steroid Rings The Westphalen and Backbone Rearrangements Epoxide Rearrangements Aromatization... 

The stereochemical requirements for backbone rearrangement of the steroid framework have been well established From deuterium-labelling experiments, the energetics and conformational dynamics of intermediate tertiary cations for model decyl systems compared with the rate of adjacent proton loss and the role and mobility of counter ion in the reaction are knownThe mechanism for formation of the rearranged isomers 87, 88, 89 and 90 with both configurations at C(20) was not investigated, but epimerization at C(20) in the total backbone rearrangement of the steroid nucleus has been previously reported . 

The 5a-configuration of the 5-chlorocholestane which results from hydrochlorination of cholest-5-ene has been confirmed by X-ray analysis. The residue from hydrochlorination of cholest-5-ene appeared to contain another compound which could not be isolated or identified as the unknown 5/8-isomer. Perhaps the possibility of its being a backbone-rearranged isomer (p. 273) should be investigated. The stereochemistry of electrophilic attack upon a A -steroid may depend critically upon subtle conformational features. Cholest-5-en-3-one, for example, reacts with bromine chloride to give products of both a- and /8-attack, whereas cholesterol is attacked almost wholly from the a-face. Discussion centres on... 

It appears that these latter results constitute the first example of such an equilibrium during an acid-catalysed isomerisation reaction in the steroid series. Isomerisation of a double bond in a steroid system is equally possible from C-10 towards C-14, as well as from C-14 towards C-10. This confirms that it is impossible to predict the outcome of a backbone rearrangement without taking into account the nature, the position, and the configuration of the groups present in the molecule. 

Peakman T.M., Jervoise A., Wolff G.A., Maxwell J.R. (1992) Acid-catalyzed rearrangements of steroid alkenes. Part 4.An initial reinvestigation of the backbone rearrangement of 4-methylcholest-4-ene. In Biological Markers in Sediments and Petroleum (ed. Moldowan J.M., Albrecht P., Philp R.P.), 58-74. Englewood Cliffs, NJ Prentice Hall. 

Two possible mechanisms have been invoked to explain backbone rearrangements in the steroid and triterpene series... 

Backbone rearrangements of various steroidal amines have been carried out in order to study the mechanism and to elucidate the stereochemistry of the rearranged products. The two 3 -dimethylamino-A -androsten-17-ones epi-meric at position 14, (33) and (34), when treated with concentrated sulphuric... 

The isomerization of some 3j8-dimethylaminosteroids, namely conessine (4), 3/3-dimethylamino-A -pregnen-20-one (49), and 3 -dimethylamino-A -andro-sten-17-one (50), in a sulphuric acid-acetic acid medium, gave 1(10- 5)-aheo-steroids and A -steroids, as well as backbone-rearranged products (Scheme 5). It was shown that A -derivatives could be eventual intermediates in the formation of 1(10 — 5)-o6eo-steroids. On the other hand, 3a-dimethylamino-steroids do not afford 1(10—> 5)-aheo-steroids under these experimental conditions an explanation is proposed. 

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