STUDIES DIRECTED TOWARD THE SYNTHESIS OF GLYCOPEPTIDE ANTIBIOTIC TEICOPLANIN - 1ST SYNTHESIS OF THE N-TERMINAL 14-MEMBERED RING

The N-terminal 14-membered ring formed by an ether linkage between the phenyl moieties of amino acids 1 and 3 of glycopeptide antibiotic teicoplanin 1 plays a crucial role in binding of C-terminal D-Ala-D-Ala residues of the peptidoglycan precursor, thereby inhibiting bacterial cell wall biosynthesis. Herein, the first stereocontrolled synthesis of this very important cyclic peptide 2 is described. The two alpha-arylglycines present in this segment are constructed in optically pure form by diastereoselective Strecker synthesis using alpha-phenylglycinol as chiral auxiliary. Finally, the coupling between the acid function of amino acid 1 and the amino function of amino acid 2 leads to the desired macrocyclization. Optical purity of the synthetic product is determined by NMR studies.