Stigmasterol-Acylglycerol Conjugates: Chemoenzymatic Synthesis as a Shorter Alternative to Chemical Routes and the Impact of Fatty Acid Chain Length on the Physicochemical Parameters of Liposomes.

In this study, a two-step chemoenzymatic route was developed for the synthesis of symmetrical acylglycerol-stigmasterol conjugates bearing a stigmasterol moiety at the sn-2 position and saturated acyl chains (decanoyl, C10, or stearoyl, C18) at the sn-1,3 positions. The use of Candida antarctica lipase B (CALB) under mild conditions (0-5 °C) ensured high regioselectivity, successfully preventing acyl migration and eliminating the need for complex protection/deprotection steps. The impact of the synthesized conjugates on DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) model lipid membranes was evaluated using dynamic light scattering (DLS), differential scanning calorimetry (DSC), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and fluorescence spectroscopy. Incorporation of the conjugates broadened the main phase transition of DPPC, reduced membrane fluidity in the liquid-crystalline phase, and limited interfacial hydration in a concentration- and chain-length-dependent manner. The short-chain derivative (C10) maintained smaller, homogeneous liposomes and disrupted lipid packing in the gel phase, whereas the longer-chain derivative (C18) promoted stronger hydrophobic interactions within the bilayer core. These findings highlight the potential of chemoenzymatically derived lipid-phytosterol conjugates for the precise tailoring of nanocarriers in functional food and nutraceutical delivery systems.