Semisynthesis of Bruceine-A Derivatives via Acylation Reaction and Its Mechanism of Reaction Potential as Antiplasmodial

AbstractBruceine A is a major quassinoid isolated from the seeds of Brucea javanica and has been reported to exhibit significant anticancer and antiplasmodial activities. Structural modification of Bruceine-A through semisynthesis is a rational approach to improve its biological potential. This study aimed to design and evaluate semisynthesized pathways for Bruceine-A derivatives and to elucidate the reaction mechanism. Two semisynthesis routes were evaluated: (i) a protection–deprotection strategy involving tert-butyldimethylsilyl chloride (TBDMS-Cl), and (ii) a direct acylation approach. Due to limitations in material availability and reaction complexity, the second pathway was selected. Direct acylation of Bruceine A in N,N-dimethylformamide (DMF) using imidazole as a base catalyst successfully yielded 3-O-chlorobenzoylbruceine (P1). Structural elucidation was performed using UV, IR, ^1H-NMR, ^13C-NMR, and LC–MS. The results demonstrate that direct acylation at the C-3 hydroxyl group is an efficient and selective strategy for the semisynthesis of Bruceine A derivatives.Keywords: Bruceine A, quassinoid, semisynthesis, acylation, Brucea javanica, 3-O-chlorobenzoylbruceine