Assessing the Optimal Deoxygenation Pattern of Dodecyl Glycosides for Antimicrobial Activity Against Bacillus anthracis

The discovery of the bactericide dodecyl 2,6-dideoxypyranoside reorganizing membrane phospholipid matrix of Bacillus species into a hexagonal phase, encouraged further research on glycone deoxygenation/bioactivity relationship. We now describe expedient syntheses of new 2-, 3-, 4-deoxy, 2,3- and 3,4-dideoxy glycosides in moderate to good yields. Interestingly, Amberlyst 15 is a key protagonist, efficiently applied for the transacetalation of alkyl deoxy glycosides and for ring contraction to access regioselectively hexofuranosides. The 2-deoxy-d-arabino pyranoside affords the higher MIC values against two Bacillus spp. and Enterococcus faecalis, while a 4-fold decrease or higher was found by inversion of configuration or by deoxygenation at C-3. While 2,3- and 3,4-dideoxygenation do not improve bioactivity, the 4,6-dideoxy-α-d-xylo-hexopyranoside remains a promising glycoside, presenting low MIC values for all species tested, and low cytotoxicity in intestinal and liver cell models.