Department of Chemical Sciences, University of Naples Federico II, Via Cintia, 80126 Naples, Italy.
Department of Pharmacy, University of Naples Federico II, Via Domenico Montesano, 49, 80131 Napoli, Italy.
Mar Drugs. 2020 Nov 19;18(11):572. doi: 10.3390/md18110572.
In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars - and - based on the one-pot conjugation of both enantiomeric forms of -butyldeoxynojirimycin (NBDNJ) and -nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I/ImH activating system, which provided the desired compounds in high yields (94-96%) by a one-pot procedure. The substantial increase in the lipophilicity of - and - is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.
为了提高亚氨基糖的抗菌活性，我们报告了脂溶性亚氨基糖的合成-和-基于-NBDNJ 和-NPDNJ 两种对映体与胆固醇和琥珀酸模型连接物的一锅接枝反应。该连接反应使用已建立的 PS-TPP/I/ImH 激活系统进行了调整，该系统通过一锅法以高收率（94-96%）提供了所需的化合物。-和-的亲脂性的显著增加，预计将改善细菌细胞内的内化，从而可能导致抗菌性能增强。然而，目前由于溶解度问题，检测受到阻碍；因此，需要设计替代给药策略。
