Sugar based surfactants are gaining increasing attention due to their medicinal applications. These molecular entities are also known for their biocompatibility and low toxicity, which make them very attractive for pharmacological applications. The active site of many biologically active amphiphilic molecules is frequently the plasma membrane and the interaction with this first barrier may determine their activity by either blocking permeation, inducing solubilization or modifying the membrane structure. Our previous studies on alkyl deoxy hexopyranosides of the d and l series in their α- and β-anomeric configurations have shown that high surface activity is a pre-requisite for their antimicrobial properties, but the specificity appeared to be linked to the anomeric configuration of the sugar and to the deoxygenation pattern. Synthesis of 2-deoxy glycosides was based on a simple but efficient methodology comprising the reaction of glycals with alcohols catalysed by triphenylphosphane hydrobromide. Chemical approaches toward further glycon deoxygenation and aglycon construction will also be presented. Glycons from d and l series and aglycons based on alkyl chains of different size, their fluorinated or branched chain analogues, and those exhibiting chains with internal amide or terminal amine functionalities as well as thioglycosides were synthesized. Their bioactivity toward Bacillus anthracis will be disclosed and surface-active properties in terms of adsorption and aggregation parameters discussed. Acute cytotoxicity studies using the MTT method have shown that some of these glycosides exhibit low toxicity when compared to chloramphenicol. An overview of the key structural features regarding glycon and aglycon chemical composition and glycon configuration for this new and non-toxic family of antibiotics will be presented, highlighting the correlation of their aggregation and adsorption physical data with the exhibited antibacterial activity.
