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 α,β-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

New Steroidal Selenides as Proapoptotic Factors

Cytostatic and pro-apoptotic effects of selenium steroid derivatives against HeLa cells were determined. The highest cytostatic activity was shown by derivative 4 (GI50 25.0 µM, almost complete growth inhibition after three days of culture, and over 97% of apoptotic and dead cells at 200 µM). The results of our study (cell number measurements, apoptosis profile, relative expression of apoptosis-related APAF1, BID, and mevalonate pathway-involved HMGCR, SQLE, CYP51A1, and PDHB genes, and computational chemistry data) support the hypothesis that tested selenosteroids induce the extrinsic pathway of apoptosis by affecting the cell membrane as cholesterol antimetabolites. An additional mechanism of action is possible through a direct action of derivative 4 to inhibit PDHB expression in a way similar to steroid hormones

PhSeZnCl in the Synthesis of Steroidal β-Hydroxy-Phenylselenides Having Antibacterial Activity

We report here the reaction of in situ prepared PhSeZnCl with steroid derivatives having an epoxide as an electrophilic functionalization. The corresponding ring-opening reaction resulted to be regio- and stereoselective affording to novel phenylselenium-substituted steroids. Assessment of their antibacterial properties against multidrug-resistant bacteria, such as Pseudomonas aeruginosa Xen 5 strain, indicates an interesting bactericidal activity and their ability to prevent bacterial biofilm formation

Synthesis, Structure, and Local Molecular Dynamics for Crystalline Rotors Based on Hecogenin/Botogenin Steroidal Frameworks

The synthesis and solid-state characterization of a series of cyclic/acyclic molecular rotors derived from naturally occurring steroidal 12-oxosapogenins are described. The bridged molecular rotors with rigid steroidal frameworks were obtained by employing ring-closing metathesis (RCM) as a key step. The X-ray diffraction technique was employed for determination and refinement of the crystal and molecular structure of selected models giving good quality single crystals. In the case of the bridged hecogenin molecular rotor <b>11</b><i><b>E</b></i> for which poor quality crystals were obtained, an NMR crystallography approach was used for fine refinement of the structure. Solid state NMR spectroscopic techniques were applied for the study of local molecular dynamics of the featured acyclic/cyclic molecular rotors. Analysis of ¹³C principal components of chemical shift tensors and chemical shift anisotropy (CSA) as well as heteronuclear ¹H–¹³C dipolar couplings (DC) unambiguously proved that aromatic rings located in the space within the rigid steroidal framework both for cyclic and acyclic rotors are under kHz exchange regime. Experimental results were confirmed by theoretical calculations of rotation barrier on the density functional theory level. Small distinctions in the values of CSA and DC for the rotors under investigation are explained on the basis of differences in their molecular structures