Simple Zn-Mediated Seleno- and Thio-Functionalization of Steroids at C-1 Position

Here we report the reaction in the biphasic system of the in situ prepared selenols and thiols with 1,4-androstadiene-3,17-dione (1) or prednisone acetate (2) having alpha,beta-unsaturated ketone as an electrophilic functionalization. The Michael-type addition reaction resulted to be chemo- and stereoselective, affording a series of novel steroidal selenides and sulfides. This is an example of a one-step, eco-friendly process that bypasses some of the main concerns connected with the bad smell and the toxicity of these seleno- and thio-reagents. Furthermore, we demonstrated that the proposed methodology offers the possibility to prepare libraries of steroids variously and selectively decorated with different organochalcogen moieties at the C1 position starting from 1,4-androstadienic skeletons and leaving unaltered the C4-C5 unsaturation. Based on the data reported in the literature the introduction of an organoselenium or an organosulfur moiety in a steroid could provide new interesting pharmaceutically active entities exerting anticancer and antimicrobial activities. In this optic, new synthetic strategies to efficiently prepare this class of compounds could be strongly desirable.

Automated summary

The study describes a chemoselective and stereoselective Michael-type addition reaction in a biphasic system to synthesize novel steroidal selenides and sulfides, demonstrating an eco-friendly one-step process that allows for the preparation of variously decorated steroids starting from 1,4-androstadiene skeletons. This methodology could potentially lead to the development of new pharmaceutically active compounds with anticancer and antimicrobial properties.