Synthesis of glucose-templated lysine analogs and incorporation into the antimicrobial dipeptide sequence kW-OBn

The synthesis of two glucose-templated (GlcT) lysine analogs GlcTK and GlcTk in which the side chain of d- and l-lysine (k and K) is conformationally constrained via incorporation into a d-glucose scaffold is described. A key-step in the synthesis is a high yielding, reductive ring opening of an exocyclic glucose-derived epoxide to form a α-hydroxy ester that can be converted into GlcTK and GlcTk. To demonstrate the use of these building blocks in peptide synthesis, we replaced d-lysine in the antimicrobial dipeptide sequence kW-OBn (W = l-tryptophan) and determined the antibacterial activity against various gram-positive and gram-negative organisms. Our results show that the replacement of d-lysine by unprotected GlcTk in dipeptide kW-OBn results in reduced antibacterial activity.

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