Androstanes rearrangement

The ready availability and low cost of A -20-keto steroids from the degradation of sapogenins has led to intensive study of methods for the preparation of androstanes via these intermediates. The simplest, most practical and most widely used method on a production scale is the Beckmann rearrangement of -20-oximinopregnenes ... 

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). 

Conversion of pregnanes to androstanes via the Schmidt Rearrangement 17/3-aminoandrost-5-en-3/3-ol, 145 Cyclobutanol formation by ketone irradiations... 

Favorskii rearrangement, 159, 176 Formation of hetero-radicals, 238 2-Formyl-A-nor-5a-androstan-l 7 -oI, 415 2-Formyl-A-nor-5 a-androst-1 -en-17 S-ol, 416 6/3-Formyl-B-nor-5 -cholestane-3, 5 -dioI 3-acetate, 432... 

This procedure appears to be general for the preparation, without rearrangement, of lesser substituted olefins. 2-Methyl-cyclohexanone tosylhydrazone gives 3-methylcyclohexene (98% yield by gas chromatography analysis).8 Cholestan-6-one tosylhydrazone gives A6-cholestene (95% isolated yield), androstan-... 

Evidence has been obtained467 for the involvement of a tertiary cyclopropylcarbinyl cationic intermediate in the rearrangement of presqualene diphosphate to squalene. 16-Oximino-17a-benzyl-17//-hydroxy derivatives in the androstane and estrane series have been converted into 16-oxo-17//-benzyl-17a-hydroxy derivatives with inversed configuration at C(17), on treatment with titanium trichloride. It has been suggested468 that the rearrangement occurs through the key intermediate (401) (see Scheme 97). 

Acetoxy-5-bromo-6/9,19-epoxy-5a -androstan-17-one undergoes rearrangement in acetic anhydride with BF3 diethyl etherate to give 3/2,19-diacetoxy-6o -bromo-5-hydroxy-5/l-androst-l 7-one after the addition of water, as shown schematically in Scheme 23.40... 

The abnormal Beckmann rearrangement displayed by the oxime of 17-oxo-5a-androstan-3/3-yl acetate (248) to yield the 13,17-seco-nitrile (249) has provided the key step in a synthetic route to 17-oxo-18-nor-5a,13/8-androstan-3/S-yl acetate and its 13a-epimer.114 The reaction sequence is shown in Scheme 12. The 17-ketone (248) was converted via its oxime into the seco-nitrile in a yield of 52%. Treatment of the oxime by the more conventional toluene-p-sulphonyl chloride reagent... 

Bromination of androstan-i6-ones is complicated by rearrangements and by dibromination, but appears to favour 17a (pseudo-axial) attack initially. Enolisation of the 16-0x0 group is slow and inefficient compared with a 17-ketone, at least when isopropenyl acetate is used [x i], although the same (A ) double bond is produced. The enol acetate bromi-nates selectively at the lya-position [152]. The alternative enol acetate (A ) is formed in minor amount, and gives the 15 -bromoketone. Both 17a- and i5) -attack correspond to pseudo-axial approach of the reagent as required by stereo-electronic factors. 

The preparation of some 16a,17a-methylene androstane (cyclopropane) derivatives, and their rearrangement to give D-homoandrostan-17a-ones, is described on p. 278. 

A similar result was observed, also in the androstane series, when the 3a-amine (404) rearranged in sulphuric acid to give an equilibrated mixture of the 10a- and 10jS-A -unsaturated compounds (405). ... 

It has been shown that 7j8-fluoro-B-homo-steroids are much more stable than their 7jS-chloro-analogues. Aromatization of ring a of such 7)S-fluoro-B-homo-androstanes and -pregnanes, under various conditions, occurred without rearrangement of the carbon skeleton and without loss of fluorine. Whereas... 

Aromatization of Rings.—A full account of the acid-catalysed aromatization (in ring a ) of 5,6-epoxyandrostan-7-ols includes an additional example in the formation of a l,4-dimethyloestra-l,3,5(10)-triene (275) from a 3a-methyl-5,6/8-epoxy-5j8-androstan-7 8-ol (274). This reaction clearly involves a skeletal rearrangement... 

Smith et at attempted to prepare a 1-fluorosteroid by the action of the reagent on lce-hydroxy-5 -androstane-3,17-dione but obtained instead three products of retropinacol rearrangement of the Ci -methyl group A -, A < >-, and A -lj8-methyl-estrene-3-ketones. 

This rearrangement can be conveniently combined with the addition of difluorocarbene to afford 3-fluorofurans directly from a, -unsaturated ketones. Treatment of 17 -benzoyloxy-2-benzylidene-5a-androstan-3-one (23) in refluxing triglyme with 30 equivalents of sodium chloro-difluoroacetate (see Section 1.A.1.2.1.4.) afforded, after column chromatography, the furan 24 in 52% yield. ... 

Steroidal amines with nitrogen at C-3 or C-20 can be converted into steroidal hormones." Beckmann rearrangement of the oxime (45) of funtumine gives 3a,17j3-diamino-5a-androstane (46). Ruschig deamination of the latter gives androstanedione In the same way, the alkaloids of H. floribunda,... 

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