Epiandrosterone synthesis

The synthesis of derivatives of steroids dihydrotestosterone 160 and epiandrosterone 161, containing indole and phosphoryl fragments, is described in the patent [156],... 

Carboxylation of ketones. In the Robinson-Cornforth1 formal total synthesis of epiandrosterone two relays were utilized. The second was the Koster-Logemann2 ketone (1), available as a by-product of the oxidation of cholesteryl acetate dibromide. Based on model experiments with alicyclic ketones, (1) was converted... 

The First total syntheses of non-aromatic S., achieved almost simultaneously in 1951 by Woodward s group ( Harvard synthesis of cortisone) and Comforth and Robinson ( Oxford synthesis of 3-epiandrosterone) were milestones in the history of chemistry. In spite of new strategies to improve the yields, none of the total... 

A second total synthesis of epiandrosterone, noteworthy because of its stereochemical control and elegant simplicity, has recently been announced by Johnson, W. 8., Bannister, B., Bloom, B. M., Kemp, A. D., Pappo, R., Rogier, E. R., and Ssmuszkovicz, J. 1953. J. Am. Chem. Soc. 76, 2276-2276. 

Abiraterone acetate 117 is an androgen biosynthesis inhibitor, which was developed by the Institute of Cancer Research in the UK and further developed by Janssen for the oral treatment of patients with metastatic castration-resistant prostate cancer [75]. Its synthesis is relatively easy through a Suzuki coupling between the 17-enol triflate derived from the 3-acetate of dehydro-epiandrosterone (115) and 3-pyridyl-diethylborane (116) (Scheme 27) [76]. The reaction is catalysed by PdCl2(PPh3)2 and proceeds in good yield (84%). A similar Suzuki-based route in which the ketone starting material was converted into an alkenyliodide has also been published [77]. 

A synthesis of 17p-amino-5oi-androstan-3ot-ol from epiandrosterone has been performed [1236]. The intermediate 17y6-isocyano-5a-androstan-3j8-ol was formed from the corresponding formamide by dehydration with p-tosyl chloride [1236]. 

The above powerful methodology was applied to the synthesis of both steroid C20 (S ) and C20 (R) derivatives from the corresponding 1,3-dienes 8 and 9 derived from two prototypical steroids, estrone and 3-epiandrosterone. By the proper choice of ligands between Feringa s phosphoramidite ligand and another phosphoramidite ligand (S,S)-10, the authors showed that it was possible to install with complete stereoselectivity either the C20 (i ) or C20 (S) configuration. As shown in Scheme 5.12, the nickel-catalysed... 

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