STRUCTURAL MODIFICATIONS OF THE ACTIVE-SITE IN TEICOPLANIN AND RELATED GLYCOPEPTIDES .2. DEGLUCOTEICOPLANIN-DERIVED TETRAPEPTIDE

The deglucoteicoplanin-derived tetrapeptide (TDTP), a key synthon suit able for the synthesis of modified glycopeptide antibiotics differing in the structure of the active site, was prepared from the product (RH -TD) of reductive hydrolysis of the 2,3-peptide bond of deglucoteicopl anin (TD) upon selective oxidation of the newly formed hydroxymethyl g roup and following simultaneous removal of amino acids 1 and 3 by doub le Edman degradation. The oxidation of the alcohol function of residue 2 in RH-TD was accomplished (Jones reagent) after protection of the t wo free amino groups as tert-butyl BOC carbamates and of most of pheno lic hydroxy groups as benzyl CBZ carbonates. Esterification of the C-t erminal carboxy group of intermediate di-BOC-RH-TD allowed the formati on at the end of the process of the tetrapeptide (TDTP-Me) protected a t one carboxy group as methyl ester. Selective protection of the prima ry N-4- and N-2-amino groups of TDTP-Me as BOC and CBZ carbamates, res pectively, followed by removal of the BOC function, afforded a more su itable intermediate (N-2-CBZ-TDTP-Me) for the synthesis of new glycope ptides.