Syntheses via diacids

In all cases, the starting material has been the bromide (3). The first method of synthesis via the diester (156) was originally developed on the basis of the 3-desmethoxy analog of the bromide (3) as early as 1934 [275, 276] and was improved in 1951 [195]. The ketodiester (156) was formed by the alkylation of the bromide (3) with the diester of )S-oxoadipic acid its cyclization and hydrolysis led to the diacid (157). Pyrolysis of the latter over lead carbonate enabled the 18-nor derivative (158) to be obtained.  

Wolff—Kizhner methods led to the corresponding isomer of dehydro-doiS5molic acid (178) [284, 285], An attempt at the direct synthesis of (178) by the condensation of the diene (169) with oj-methyl-/ -acrylic acid was unsuccessful because of the undesirable structural directivity [286]. A repetition of the Arndt—Eistert reaction with (175) and Dieckmann cy-clization of the diester obtained (176) yielded the cis-C/D isomer of 8(9)-dehydroestrone (179) [287]. Dehydrogenation of the adduct (173) led to a naphthalene derivative (174), opening of the anhydride ring in which gave the semiester (177). The methyl ether of cis-equilenin (37) was obtained from the latter by two extensions of the side chain by the Arndt—Eistert reaction and by cyclization [283]. 

Condensation of the diene (169) with diacetylethylene led to the adduct (166), which is a mixture of the and -isomers. Hydrogenation 

The second type of total synthesis of steroids from AB fragments comprises the simultaneous introduction of rings C and D into the molecule by the diene condensation of vinylbicyclenes with cyclic dienophiles (Table 6). This synthetic route is, at first sight, extremely simple, since all or almost all the required carbon atoms are introduced in a single stage and only the problem of ensuring the required stereochemistry and structure remains. However, because of the fundamental properties of the diene synthesis this problem becomes the stumbling block and its solution has not been effected in by any means all cases. 

Condensations of Aromatic Dienes. Here we consider the condensations with cyclic dienophiles of dienes of the type of 1-vinyl- 

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Syntheses via Diacids. Several variants of the total synthesis of equilenin derivatives are known in which the intermediate products are tricyclic diacids formed, in their turn, by the cyclization of oj-naphthyl-substituted long-chain keto acids (Scheme 15 see also Schemes 6 and 7). 

Syntheses via Diacids. The reduction of methyl m-metho y-cinnamate (536) with amalgamated aluminum leads to a mixture of diesters of the meso- and adipic acid in a ratio of 4 3 (Scheme 52) [605-607]. The configuration of the latter was shown by its resolution into antipodes via the brucine salts [605]. The cyclization of the acid chlorides of each of the isomers with subsequent hydrogenolysis of the 6- and 12-oxo groups led to hexahydrochrysene. In this process, the meso-form gave the trans-B/C derivative (540) and the dlAormthe cis-B/C derivative (541) [605],... 

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