The p-aminobenzoate moiety has been demonstrated as a potent substructure in medicinal chemistry. Several derivatives have been synthesized and their antibacterial and anticancer activities have been analyzed, yielding promising results.
In glycodrugs, the specific biological activity cannot be exclusively attributed to the aglycone moiety. It has been well demonstrated that the sugar residue may play a crucial role in therapeutic efficiency by modifying transport through various biological barriers or interacting with receptors or lectins on the cell surface.
In the present work, we investigate the synthesis and structural analysis of novel benzocaine and procaine glyco derivatives. The molecule design incorporates two principles: the attachment of the bioactive aglycone at a non-anomeric position and through a nitrogen atom; these structural features generate novel compounds that differ from classical O-glycosides, thereby creating molecular diversity to achieve more accurate structure-activity relationships.
We synthesized 6-N-galactosyl derivatives of p-aminobenzoate using a four-step methodology in good yields. The oxidation of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose with DMSO/DCC yielded the corresponding galactosyl aldehyde. This aldehyde subsequently reacted with arylamines (benzocaine or procaine) in dichloromethane, forming the Schiff bases. The imine functional group was then reduced with NaBH4 in isopropanol. The resulting galactosyl derivatives of procaine and benzocaine were fully characterized using NMR spectroscopy. A comprehensive conformational analysis was also conducted, analyzing 1H NMR coupling constants and comparing the results with previously reported 6-deoxy-6-N-aryl-D-galactosides.
