Structural modifications of the active site in teicoplanin and related glycopeptides. 2. Deglucoteicoplanin-derived tetrapeptide

Article abstract of DOI:10.1021/jo9506746

The deglucoteicoplanin-derived tetrapeptide (TDTP), a key synthon suitable 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 deglucoteicoplanin (TD) upon selective oxidation of the newly formed hydroxymethyl group and following simultaneous removal of amino acids 1 and 3 by double Edman degradation. The oxidation of the alcohol function of residue 2 in RH-TD was accomplished (Jones reagent) after protection of the two free amino groups as tert-butyl BOC carbamates and of most of phenolic hydroxy groups as benzyl CBZ carbonates. Esterification of the C-terminal carboxy group of intermediate di-BOC-RH-TD allowed the formation at the end of the process of the tetrapeptide (TDTP-Me) protected at one carboxy group as methyl ester. Selective protection of the primary N⁴- and N²-amino groups of TDTP-Me as BOC and CBZ carbamates, respectively, followed by removal of the BOC function, afforded a more suitable intermediate (N²-CBZ-TDTP-Me) for the synthesis of new glycopeptides.