Department of Chemistry, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago.
Department of Life Sciences, The University of the West Indies, St. Augustine Campus, Trinidad and Tobago.
Carbohydr Res. 2021 Feb;500:108216. doi: 10.1016/j.carres.2020.108216. Epub 2020 Dec 5.
Phosphoramidates are becoming increasingly recognized as molecular targets for therapeutic development. Their biological functions are significantly influenced by their inherent properties such as reactivity, as well as the P-N backbone which allows for structural diversity. In this study we report the synthesis of novel carbohydrate-based phosphoramidate derivatives via the Staudinger-phosphite reaction; along with an evaluation of their adjuvant activity in combination with popular antibiotics. Our targets involved variation in both the sugar residue as well as the identity of the phosphoramidate. Moderate to excellent yields of these derivatives were obtained. Notable adjuvant activity was observed with the halogenated phosphoramidates. For the fluorinated glucose derivative in particular, a remarkable 32-fold decrease in the MIC of Ampicillin was obtained against Methicillin-resistant S. aureus.
膦酰胺酯类化合物作为治疗靶点越来越受到重视。其生物学功能受固有性质（如反应活性）和允许结构多样性的 P-N 骨架的显著影响。在这项研究中，我们通过 Staudinger-亚磷酸酯反应报告了新型基于碳水化合物的膦酰胺酯衍生物的合成；并评估了它们与常用抗生素联合使用的佐剂活性。我们的目标涉及糖残基和膦酰胺酯的身份的变化。这些衍生物的产量适中到优异。卤代膦酰胺酯表现出显著的佐剂活性。特别是对于氟化葡萄糖衍生物，获得了抗耐甲氧西林金黄色葡萄球菌的氨苄青霉素 MIC 值降低了 32 倍。
