Rhamnopyranoside-Based Fatty Acid Esters as Antimicrobials: Synthesis, Spectral Characterization, PASS, Antimicrobial, and Molecular Docking Studies.

The most widely used and accessible monosaccharides have a number of stereogenic centers that have been hydroxylated and are challenging to chemically separate. As a result, the task of regioselective derivatization of such structures is particularly difficult. Considering this fact and to get novel rhamnopyranoside-based esters, DMAP-catalyzed di- O -stearoylation of methyl α-l-rhamnopyranoside ( 3 ) produced a mixture of 2,3-di- O - ( 4 ) and 3,4-di- O -stearates ( 5 ) (ratio 2:3) indicating the reactivity of the hydroxylated stereogenic centers of rhamnopyranoside as 3-OH > 4-OH > 2-OH. To get novel biologically active rhamnose esters, di- O -stearates 4 and 5 were converted into six 4- O - and 2- O -esters 6 - 11 , which were fully characterized by FT-IR, 1 H, and 13 C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides 6 - 11 with maximum lipophilic character showed better antifungal susceptibility than antibacterial activity. These experimental findings are similar to the results found from PASS analysis data. Furthermore, the pentanoyl derivative of 2,3-di- O -stearate (compound 6 ) showed better antifungal functionality against F. equiseti and A. flavus , which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters 4 - 11 was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of 10 (-7.6 kcal/mol), 9 (-7.5 kcal/mol), and 7 (-6.9 kcal/mol) were better and comparable to fluconazole (-7.3 kcal/mol), indicating the likelihood of their use as non-azole type antifungal drugs in the future.