Novel <span style="font-variant: small-caps">d</span>-Annulated Pentacyclic Steroids: Regioselective Synthesis and Biological Evaluation in Breast Cancer Cells

Abstract

The acid-catalyzed cyclization of benzylidenes based on 16-dehydropregnenolone acetate (16-DPA) was studied. It was found that these compounds readily undergo regioselective interrupted Nazarov cyclization with trapping chloride ion and an efficient method of the synthesis of d-annulated pentacyclic steroids based on this reaction was proposed. The structures of the synthesized pentacyclic steroids were determined by NMR and X-ray diffraction. It was found that the reaction affords a single diastereomer, but the latter can crystallize as two conformers depending on the structure. Antiproliferative activity of synthesized compounds was evaluated against two breast cancer cell lines: MCF-7 and MDA-MB-231. All tested compounds showed relatively high antiproliferative activity. The synthetic potential of the protocol developed was illustrated by the gram-scale experiment.

Keywords

• interrupted Nazarov cyclization
• pentacyclic steroids
• antiproliferative activity
• d-annulated steroids%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <span style="font-variant: small-caps">d</span>-annulated steroids
• Lewis acid