Synthesis of β-aminoacrylated betulin derivatives by a spontaneous amino–yne reaction for antifungal applications

Abstract

Betulin, a lupane-based pentacyclic triterpenoid, is renowned for its sustainability and potent antifungal properties. By leveraging a spontaneous amino–yne reaction in conjunction with betulin, novel biomolecules representing a diverse library of triterpenoid derivatives are designed and synthesized for potential antifungal development. In this work, betulin was initially transformed into 28-propynoylbetulin via a traditional DCC coupling reaction. Subsequently, mono- and di-β-aminoacrylated betulin derivatives were synthesized by reacting betulin with various secondary (di)amines via an amino–yne chemistry. All the compounds were identified by ¹H, ¹³C NMR, HR-MS, and FT-IR analyses, and their antifungal properties were evaluated. The versatility of these betulin derivatives in accommodating a wide range of N-substituents has identified them as promising antifungal agents. These findings illustrate an innovative approach for enhancing the antifungal properties of betulin through β-aminoacrylation, thereby enriching its utility in biomedical applications and promoting the sustainable utilization of bioresources. This study demonstrates that combining an amino–yne reaction with biocompounds facilitates the development of novel biomolecules, indicating their potential for application in the biomedical field and advancing the sustainable development of antimicrobial compounds.