Route-selective enzymatic synthesis and structural elucidation of monooctanoylgalloylglycerols as amphiphilic...

Monooctanoylgalloylglycerols (MOGGs) are monoacylated galloyl structured lipids that combine the phenolic hydroxyl groups of gallic acid with a medium fatty-acyl chain. Their lipase-catalyzed preparation is limited by competing acyl transfer, hydrolysis, and secondary acylation reactions. This work compared several Candida antarctica lipase B-catalyzed routes using Lipozyme® 435, including transesterification of propyl gallate with mono/diacylglycerols, hydrolysis/alcoholysis of dioctanoylgalloylglycerols (DOGG), one-pot conversion of propyl gallate, glycerol, and octanoic acid (OA), and direct esterification of 1-o-galloylglycerol (GG) with OA. Only GG direct esterification gave substantial MOGG formation. Optimization using response surface methodology (RSM) identified 65 °C, an OA/GG molar ratio of 3:1, 72 h, and 30 g/L enzyme as suitable conditions, giving 62.7 ± 2.1% MOGG yield and 13.4 ± 0.3% DOGG formation. The purified MOGG fraction was characterized by FT-IR, Raman spectroscopy, NMR spectroscopy, and ESI-HRMS/MS. FT-IR and Raman spectra showed retention of galloyl features together with the introduction of octanoyl-chain signatures, while NMR and ESI-HRMS/MS confirmed the formation of two positional MOGG isomers. Docking was used to compare substrate accommodation within the lipase active site. These results identify GG direct esterification as the preferred route for controlled monoacylation of galloyl structured lipids and define the main reaction constraints affecting MOGG production.