Synthesis and Antimicrobial Activity of Novel 3-Benzyloxy-4-Substituted-2- Azetidinones: Formation of a Hydrophobic Layer Via a Self-Organization Effect

Abstract

We report the synthesis of new persulfide-spacer N-substituted-2-azetidinone-D-glucosamine in an attempt to potentially provide new antibiotics. The Schiff base ligands considered for this study were derived from D-glucosamine and 2-hydroxybenzaldehyde, 4-methoxy-benzaldehyde, cinnamaldehyde, 4-chlorobenzaldehyde, and 4-hydroxy-3-methoxy-benzaldehyde. Staudinger [2+2] cycloaddition of benzyloxyacetyl chloride to the newly reported per-O-allyl-N-substituted benzylidene-2-deoxy-β-D-glucosamine provided the sugar-based monocyclic β-lactams in moderate yields. Radical addition of 2-mercaptoethanol catalyzed by azobisisobutyronitrile to the per-O-allyl-N-substituted-2-azetidinone-D-glucosamine led to the corresponding persulfide-spacers in good yields. All new compounds were characterized by spectroscopic and spectrometric methods. The scanning electron microscopy image of 1,3,4,6-tetra-O-[3-(hydroxythioethyl)-propyl]-2-deoxy-2-N-[(3-benzyloxy-4-(4-chloropenyl)-2-azetidinone]-β-D-glucopyranoside, as a representative example, demonstrated a super hydrophobic layer formed via highly organized thioether spacers on gold as the adsorbate system through the formation of sulfur–gold bonds. The reported glucosides showed a moderate antifungal activity against Candida albicans while being slightly to moderately active against gram-positive and gram-negative bacteria used in this investigation at a concentration of 1 mg/mL dissolved in dimethyl sulfoxide.Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.GRAPHICAL ABSTRACT