Diazo Transfer−Click Reaction Route to New, Lipophilic Teicoplanin and Ristocetin Aglycon Derivatives with High Antibacterial and Anti-influenza Virus Activity: An Aggregation and Receptor Binding Study

Abstract

Semisynthetic, lipophilic ristocetin and teicoplanin derivatives were prepared starting from ristocetin aglycon and teicoplanin psi-aglycon (N-acetyl-D-glucosaminyl aglycoteicoplanin). The terminal amino functions of the aglycons were converted into azido form by triflic azide. Copper catalyzed 1,3-dipolar cycloaddition reaction with lipophilic alkynes resulted in the title compounds. Two of the teicoplanin derivatives showed very good MIC and MBC values against various Gram-positive bacteria, including vanA enterococci. The aggregation and interaction of a n-decyl derivative with bacterial cell wall components was studied. One of the lipophilic ristocetin derivatives displayed favorable anti-influenza virus activity.