Synthesis of S-Linked Glycoconjugates of Monosaccharides and Levoglucosenone Derivatives Through Photoinduced Thiol–Ene Reaction Mediated by 4CzIPN and Its Water Soluble Analog

Herein, we report a photoinduced thiol–ene reaction for the synthesis of S-linked glycoconjugates derived from levoglucosenone and related renewable glycosyl scaffolds (cyrene, levoglucosenone, and aminocyrene). They were converted into the corresponding thiol derivatives through novel synthetic routes inspired by standard sugar chemistry. Thus, the resulting thiols were efficiently engaged in photocatalyzed hydrothiolation reactions using the TADF (thermally activated delayed fluorescence) compound 4CzIPN under mild visible-light irradiation, affording a library of S-linked glycomimetic products in high to quantitative yields with the allyl alcohol, tetraethyl ethene-1,1-diylbis(phosphonate), and Fmoc-protected allyl glycine derivative as acceptors. The protocol was further translated to aqueous conditions by employing a water-soluble 4CzIPN analog, enabling the direct functionalization of deprotected thiol derivatives with acrylamide in water. Finally, the methodology was successfully extended to conventional gluco-, galacto-, and manno thiosugar analogs, demonstrating broad applicability, excellent functional group tolerance, and compatibility with both protected and unprotected carbohydrate substrates.