Bioorganic and Medicinal Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Chittagong, Chittagong 4331, Bangladesh.
Wazed Miah Science Research Centre (WMSRC), Jahangirnagar University, Savar, Dhaka 1342, Bangladesh.
Molecules. 2023 Jan 18;28(3):986. doi: 10.3390/molecules28030986.
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.
最常用和易获得的单糖具有许多手性中心，这些手性中心已被羟化，难以通过化学方法分离。因此，对这些结构进行区域选择性衍生化的任务特别困难。考虑到这一事实，并获得新型鼠李吡喃糖苷基酯，在 DMAP 催化下，对甲基 α-L-鼠李吡喃糖苷（）进行二--硬脂酰化反应，生成 2,3-二--（）和 3,4-二--硬脂酸酯（）（比例 2:3）混合物，表明鼠李吡喃糖苷中羟化手性中心的反应性为 3-OH > 4-OH > 2-OH。为获得新型具有生物活性的鼠李糖酯，二--硬脂酸酯和通过酯化反应转化为六个 4--和 2--酯 - ，并用 FT-IR、H 和 C NMR 光谱技术对其进行了全面表征。体外抗菌试验表明，完全酯化的鼠李吡喃糖苷 - 具有最大的亲脂性，显示出比抗菌活性更好的抗真菌敏感性。这些实验结果与 PASS 分析数据的结果相似。此外，2,3-二--硬脂酸酯的戊酰衍生物（化合物）对和具有更好的抗真菌功能，比标准抗生素更好。为了验证更好的抗真菌结果，对鼠李糖酯 - 进行了分子对接，对接蛋白为羊毛甾醇 14α-去甲基酶（PDB ID：3LD6），包括标准抗真菌抗生素酮康唑和氟康唑。在这种情况下，-7.6 kcal/mol）、-7.5 kcal/mol）和-6.9 kcal/mol）的结合亲和力更好，与氟康唑（-7.3 kcal/mol）相当，表明它们未来有可能作为非唑类抗真菌药物使用。
