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.

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GRAPHICAL ABSTRACT

Keywords:

• D-Glucosamine
• sulfide spacer
• antibiotics