Betulinic acid (BA) is a kind of naturally occurring lupane pentacyclic triterpenoid, possessing various biological activities including antiviral, anti-inflammatory and antitumor activity. Covalent inhibitors, characterized by electrophilic warheads that form covalent bonds with specific amino acid residues of target proteins, have garnered enormous attention in anticancer agent discovery over the past decade owing to their exceptional selectivity and efficacy. In this study, BA was structurally modified with electrophilic groups, and 23 derivatives of BA were synthesized. Most of these BA derivatives exhibited improved antiproliferative activity against MCF-7, HeLa, MDA-MB-231 cells in MTT assay, especially the compound 15b (IC