Guanidine-Based Azines from N-Heterocyclic Carbene (NHC)-Derived Selenoureas and Diazo Compounds: Synthesis, Structural Diversification, and Biological Evaluation

Abstract

Guanidine-based azines combine two functional groups in their structure, both of which are widely encountered in medicinal chemistry. Such molecules are accessible, among others, via the versatile reaction of N-heterocyclic carbene (NHC)-derived selenoureas with diazo compounds. Our present work introduces a highly efficient version of this transformation, simultaneously expanding its structural scope beyond the currently known ester-containing analogues. By utilizing a broad scope of diazo compounds, bearing amide, ketone, or heteroatom rich functionalities, we access various azine derivatives of biological significance. Key innovations of this new synthetic protocol include the use of polystyrene-supported triphenylphosphine as a recyclable reagent, enabling a streamlined purification process, eliminating the need for column chromatography, and allowing its repeated use under ambient conditions. Post-synthetic functionalization strategies further expand the structural diversity of the azine scaffold, and preliminary biological evaluation identifies several compounds with in vitro anti-cancer activity. The findings highlight guanidine-based azines as a promising scaffold for further chemical and biological exploration.