Synthesis and conformational study of triazole-linked bis-spirostanic conjugates

Abstract

A general approach based on the CuI-catalyzed azide–alkyne 1,3-dipolar cycloaddition reaction was implemented for the conjugation of two spirostanic steroids. This process provides rapid access to a small library of triazole-based bis-spirostanic conjugates with varied functionalization patterns as well as different stereochemistry of the linkage. The approach proved high efficiency even with the use of sterically hindered 3α-azido-spirostanes. A molecular modeling study was performed to determine the conformational characteristics of the bis-spirostanic conjugates as well as to address the structural resemblance with the potent anticancer bis-spirostanic conjugates cephalostatins and ritterazines. Considering its efficiency and versatility, this approach shows promise for the discovery of novel bis-steroidal conjugates with applications in medicinal chemistry.