Abstract
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.