J Sci Food Agric. 2026 Aug 20. doi: 10.1002/jsfa.71008. Online ahead of print.

ABSTRACT

BACKGROUND: Phytosterols, particularly β-sitosterol, exhibit well-recognized cholesterol-lowering activity; however, their practical application is constrained by rigid molecular structures and limited structural tunability. Rational molecular modification combined with the introduction of flexible linkers may provide an effective approach to improve their physicochemical and functional properties.

RESULTS: In this study, a novel sitosteryl ethylene glycol succinate containing a flexible spacer was successfully synthesized via a chemo-enzymatic approach. Under the selected enzymatic conditions (55 °C, 84 h and a substrate molar ratio of 1:2), the esterification rate reached 91.54 ± 1.80%. The chemical structure of the synthesized ester was confirmed using multiple analytical techniques. Analysis of physicochemical properties suggested that the introduction of the flexible ethylene glycol segment altered the crystalline packing and solid-state organization of β-sitosterol. In vitro micellar assays indicated that the derivative enhanced cholesterol-lowering potential relative to β-sitosterol, as evidenced by reduced cholesterol incorporation into mixed micelles.

CONCLUSION: These results suggest that the incorporation of polar and flexible spacer segments may modulate the amphiphilic balance and structural characteristics of phytosterols, thereby improving their capacity to inhibit cholesterol solubilization. This study provides a potential strategy for the rational design of phytosterol derivatives with improved functional performance. © 2026 Society of Chemical Industry.

PMID:42625287 | DOI:10.1002/jsfa.71008