Temperature-controlled, chromatography-free synthesis of allobetulin derivatives via trifluoroacetic acid-mediated Wagner-Meerwein rearrangement

Allobetulin derivatives are bioactive lupane-type triterpenoids with promising antiviral, anticancer and anti-inflammatory activities. Conventional synthetic routes rely on harsh acidic conditions and tedious column chromatography purification, leading to low scalability and significant product loss. This study describes a streamlined, one-pot protocol for the synthesis of five allobetulin derivatives from readily available betulin, betulinic acid or betulonic acid, using trifluoroacetic acid (TFA) as a dual-function catalyst and reaction medium. Product selectivity is precisely controlled by reaction temperature, eliminating the need for modifying the reagent system. The method delivers 90-95% isolated yield without chromatographic purification, and the crude product purity exceeds 95% by NMR analysis.•Temperature-dependent selectivity enables access to either C3 free alcohols or C3 trifluoroacetate esters without altering the reaction formulation•Chromatography-free workup minimizes product loss and simplifies isolation for preparative-scale synthesis•Broad substrate scope covering three representative lupane-type triterpenoid scaffolds.