A-Nor-B-Homosteroids

5-dione acetate (126a) via ketol (125) followed by dehydration.  

Velluz and co-workers named these compounds 19-nor-flfce )-steroids recognizing two possible types, i.e., 0 5A)abeo (127) and 5 0- )abeo (128).  

17jS-Hydroxy-10(5 4)a eo-estr-4(10)-ene-3,5-dione Acetate (126a) (/) 

A stream of ozone is passed into a solution of 17j5-hydroxyestr-5(10)-ene-3-one acetate (123a, 4.2 g) in methylene dichloride (17 ml) and methanol (20 ml) 

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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. ... 

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. 

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 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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