Steroids aromatization rearrangement

Steroid aromatic rearrangement.1 When (1), derived from cholic acid, is dissolved in methanol, and hydrogen chloride is passed in for 4 hr., the aromatic steroid (2) is obtained in high yield. 

The photolysis of nitrosopregnone steroid (117) afforded the 18,20-benzo-fused compound (118) as the major product (24%) along with the diol (119) (6%), whilst the expected C(18) rearranged product (120) is not isolated (Scheme 17).277 Reaction proceeds via the C(18) alkyl radical (121), formed in accordance with the accepted C(ll) O—NO bond homolysis and H-abstraction pathway, before either addition of C(11) radical (121) to the aromatic ring to afford (118) or H abstraction to give (119). 

Acid-catalysed rearrangement/hydrolysis of the 3a,20a-disulphate (168) gave the 17/3-methyl-18-nor-compound (169). Rearrangement of the 17a-hydroxy-3-oxo-A -triene (170) to the c-ring aromatic compound (171) occurred in formic acid as did the rearrangement of 17a-ethynyloestradiol to the chrysene derivative (172). The 9,ll-epoxy-17-hydroxy-steroids (173) and (174) were converted with BF3-Et20 into the C-ring aromatic compounds (175) and (176) respectively. " Normal acetonide formation in the reaction of... 

A novel route to the ring b aromatic anthrasteroids (49) from S,7-dienes (50) proceeds in two steps and uses 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) as the oxidant, as is shown in equation (47)7 Addition of PTAD to the steroidal S,7-diene gives an adduct which, when treated with boron trifluoride etherate, rearranges to the anthrasteroid in generally greater than 90% yield. This reaction presumably proceeds through a spirocyclohexa-1,4-diene. 

A further route to compounds with an aromatic ring A lies in an unusual acid-catalysed rearrangement of steroidal A -3-ketones. Testosterone (35) is reported to give the 4-methyl aromatic compound (36) with trichloroacetic anhydride in the presence of toluene- -sulphonic acid [178]. The mechanism of this reaction is not clear. 

Ring C aromatization of steroids Treatment of 17a-methyl-A - " "-testosterone (1) with 90%, formic acid under rdlux for 15 hr. results in formation of the rearranged 17,17 -dimethylandrosta-4,8,ll,13-tetraene-3-one (2) in 45% yield. 

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). 

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... 

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

Hydrolytic cleavage of the C-O bond of bicyclic, tetracyclic, and steroidal enolates with HF-SbFs induces their isomerization to the corresponding ketones (Scheme 14.41) [104]. Rearrangement of dienones to aromatic compounds is also promoted by HF-SbFs (Scheme 14.42) [105]. Ring expansion of methyl penicilli-nates is achieved by SbCls to give thiazepine derivatives [106]. 1,3-Dithianes derived from ketones and aldehydes are deprotected with SbCls by means of a single-electron-transfer mechanism [107]. 

The latter effect can especially be seen for the shifted residue Tyr , which is part of the newly formed helix in loop l, and for altered side chain conformations of Phe and Trp at the bottom of the hgand pocket. These two conserved residues have rotated their aromatic side chains by approximately 120° compared with BBP, thus enabling accommodation of the new bulky steroid hgand. Their conformation appears to be similar in aU three DigA16 structures, even in the absence of the hgand. Apparently, the side chain rotation of Trp is in concert with the extensive rearrangement in the upper part of the binding cleft, particularly within loop l due to the mutated residues. 

As Cope substrates derived from 5 are highly reactive, aromatic double bonds can also be involved in the rearrangement. Thus, steroid analogs can be prepared from a-naphthyl derivatives 291060, and the benzofuran derivative 31 is used in the synthesis of coronafacic acid 638, 1066. 

The venerable dienone-phenol rearrangement (3-1 3-2) offers another way for preparing steroids with an aromatic A-ring (Scheme 3.3). The simplest case of this method illustrates a serious drawback to this approach one of the geminal methyl groups shifts onto the adjacent position. 

---