B-homosteroids

B-Homosteroids were first reported by Ringold in the course of an investigation of the relationship of structural changes to biological activity of anabolic agents. The Tiffeneau rearrangement sequence described earlier for the preparation of A-homosteroids was used to synthesize 17/ -hydroxy-B-homo-5a-androstan-3-one (56a). 

In a study of the stereochemistry of the B-homosteroid ring system, Kohout, Fajkos and Sorm prepared 3 -hydroxy-B-homo-5a-cholestan-7-one acetate... 

B-Homosteroids have also been prepared by acid-catalyzed reaction of diazomethane with a,/5-unsaturated ketones. 3/ -Hydroxycholest-5-en-7-one acetate (57) reacts with diazomethane in the presence of concentrated fluoroboric acid, boron trifluoride etherate or aluminum chloride to give 3yS-hydroxy-B-homo-cholest-5-en-7a-one acetate (67). The 7a-keto group is reported to be chemically less reactive than an 11-keto group. 

For the preparation of 19-nor-B-homosteroids Tadanier s acetolysis procedure appears to be the method of choice. The mild reaction conditions employed with each of these procedures allows the maintainance of a variety of functional groups, e.g., double bonds, ethers, hydroxyls and the like during the homologation process. 

A-nor-5a-cholestan-2-one, 419 B-norcholestenone, 430 19-Norcholestenone, 281 B-norcholesterol acetate, 429, 430 D-nor-11-dehydrocorticosterone acetate, 441 D-nordesoxycorticosterone acetate, 441 A-nor-B-homosteroids, 395 C-nor-D-homo steroids, 400 C-nor-1U- (a-hydroxyethyl) -pregnane-... 

Spectral studies have shown the configuration of the major (377) and minor (378) A-nor-B-homosteroids formed in the acid-catalysed cyclisation of (376), to be as shown. ... 

Potent inhibition of maize A > -steroI A -reductase by novel 6-aza-B-homosteroids and other analogs of a presumptive carbocationic intermediate of the reduction reaction. 

Johnson has developed two linear approaches to synthesize the C-nor-D-homosteroid skeleton (Scheme 2.2). In his first approach [21], tetralone 19, obtained from reduction of 2,5-dimethoxynaphthalene, was used as the source of the C,D-rings. The B- and A-rings were constructed by sequential Robinson annulations (19 —> 20 —> 21). The Cl 1,12 olefin was then introduced to provide 22. Ozonolysis of 22 followed by an aldol reaction of the resulting dialdehyde gave 23. Subsequent deformylation and deoxygenation afforded the cyclopamine skeleton 24. 

A valuable extension of the diazomethane reaction for the preparation of A-homosteroids was discovered by Johnson, Neeman and Birkeland9 b who found that a, -unsaturated ketones are homologated by reaction with diazomethane in the presence of either fluoroboric acid or boron trifluoride. The main product is formed by the insertion of a methylene group between the carbonyl group and the unsaturated a-carbon to give a /, y-un saturated ketone. 

Heterocyclic Steroids - Much synthetic work continues to be published in this area. Two non-basic aza steroids, 13-aza-17-ketones, were prepared with the stated purpose of testing a hypothesis that the usual lack of hormonal activity of azasteroids is due to an Inability of basic steroids to penetrate cell membranes. However, no biological information was given.Some 15-aza-, 15,l6-diaza-, and 11,15,16-triazasterolds ° were synthesized. The former two types are reported to have anti-bacterial activity, whereas 17a-aza-0-homosteroids are inactive.The acetylation of one inactive 173-hydroxy-4-azasteroid was shown to confer anti-bacterial activity to the compound, but this effect was not general. The syntheses of a 5,10-diazasterold and of an A,B-indolo-steroid (14) were also reported. The successful preparations of 2-oxa,... 

A proof of the structure of the adduct (235) and all the intermediates in the synthesis of the D-homosteroid (237) was obtained by carrying out from (238) a stereospecific synthesis of 18-nor-D-homoandrostane-3/3, 17a/5-diol (242) [326]. The addition of h3q)obromous acid totheA )-bond of compound (238) led to the 9o -bromide (240) which was converted into the 11,15-diketone (241). The elimination of both 0x0 groups by the hydrogenolysis of the ethylene thioketals led to the diacetate (242) which, like the diol obtained from it, proved to be identical with the products synthesized by the CD—B— A route [356]. 

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