Chemo-enzymatic synthesis of G1-monoacrylate and derived amphiphiles with β-thiopropionate ester linker for drug delivery applications.

pH-labile linkers have garnered significant attention in biomedical applications, particularly in designing the stimuli-responsive carriers for targeted drug delivery systems. In the present work, we have synthesized G1-monoacrylate from G1-diacrylate using a chemoenzymatic approach, followed by the synthesis of glycerol-based β-thiopropionate esters containing an acid-labile β-thiopropionate linker. The β-thiopropionate esters were obtained via a solvent-free Michael addition reaction between hydrophobic thiol and hydrophilic G1-monoacrylate. The reaction conditions and purification by simple solvent extraction, without the need for sophisticated chromatographic techniques, provide a significant advantage for potential biomedical and other applications. The resulting β-thiopropionate esters hold significant potential for biomedical applications, particularly in the encapsulation and controlled release of hydrophobic therapeutics in acidic microenvironments.