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--stearoylation of methyl α-l-rhamnopyranoside () produced a mixture of 2,3-di-- () and 3,4-di--stearates () (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--stearates and were converted into six 4-- and 2--esters -, which were fully characterized by FT-IR, H, and C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides - 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--stearate (compound ) showed better antifungal functionality against and , which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters - was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of (-7.6 kcal/mol), (-7.5 kcal/mol), and (-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.