| Summary: | 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-<i>O</i>-stearoylation of methyl α-<span style="font-variant: small-caps;">l</span>-rhamnopyranoside (<b>3</b>) produced a mixture of 2,3-di-<i>O</i>- (<b>4</b>) and 3,4-di-<i>O</i>-stearates (<b>5</b>) (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-<i>O</i>-stearates <b>4</b> and <b>5</b> were converted into six 4-<i>O</i>- and 2-<i>O</i>-esters <b>6</b>–<b>11</b>, which were fully characterized by FT-IR, <sup>1</sup>H, and <sup>13</sup>C NMR spectral techniques. In vitro antimicrobial assays revealed that fully esterified rhamnopyranosides <b>6</b>–<b>11</b> 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-<i>O</i>-stearate (compound <b>6</b>) showed better antifungal functionality against <i>F. equiseti</i> and <i>A. flavus</i>, which were found to be better than standard antibiotics. To validate the better antifungal results, molecular docking of the rhamnose esters <b>4</b>–<b>11</b> was performed with lanosterol 14α-demethylase (PDB ID: 3LD6), including the standard antifungal antibiotics ketoconazole and fluconazole. In this instance, the binding affinities of <b>10</b> (−7.6 kcal/mol), <b>9</b> (−7.5 kcal/mol), and <b>7</b> (−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.
|
|---|