| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2029368 | Steroids | 2011 | 11 Pages |
3,17-Dicarboxamido-androst-3,5,16-triene, 3-carboxamido-androst-3,5-dien-17-one, 17-carboxamido-androst-4,16-dien-3-one and 11-carboxamido-androst-5,9(11)-dien-3,17-dione derivatives were synthesized in homogeneous carbonylation reactions from the corresponding 3,17-diiodo-androst-3,5,16-triene, 3-iodo-androst-3,5-diene-17-ethylene ketal, 17-iodo-androst-5,16-dien-3-ethylene ketal, 11-iodo-androst-5,9(11)-diene-3,17-bis(ethylene ketal) derivatives, respectively. A highly chemoselective palladium-catalyzed aminocarbonylation of the corresponding iodo-alkene, carried out under mild reaction conditions, can be considered as the key-step for the introduction of the carboxamide functionalities. The synthesis of the iodo-alkene substrate is based on the transformation of the corresponding keto derivative to hydrazone, which was treated with iodine in the presence of a base (1,1,3,3-tetramethyl guanidine). The aminocarbonylation reaction is highly tolerant towards the N-nucleophiles, i.e. various primary and secondary amines including amino acid methyl esters can also be used.
Graphical abstractAndrostane derivatives possessing iodo-alkenyl moiety(ies), obtained from 3-, 11- and/or 17-keto functionalities, were transformed into the corresponding carboxamides in palladium-catalyzed aminocarbonylation. The systematic synthesis of carboxamides with keto groups in various positions, providing a site for further functionalization, was carried out using ketals as protecting groups.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights▶ Androstane-based carboxamides which can be considered as close analogues of 5α-reductase inhibitors of pharmacological importance were synthesized. ▶ Palladium-catalyzed aminocarbonylation of iodoalkene moieties was used as a keyreaction which tolerates various functionalities as well as N-nucleophiles. ▶ The reactions are highly chemoselective and high-yielding, therefore are of direct synthetic interest.
