Structural Modifications of the Active Site in Teicoplanin and Related Glycopeptides. 2. Deglucoteicoplanin-Derived Tetrapeptide

• Published in: Journal of organic chemistry 1996-03, Vol.61 (6), p.2151-2157
• Main Authors: Malabarba, Adriano, Ciabatti, Romeo, Maggini, Michele, Ferrari, Pietro, Colombo, Luigi, Denaro, Maurizio
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• 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 N 4- and N 2-amino groups of TDTP-Me as BOC and CBZ carbamates, respectively, followed by removal of the BOC function, afforded a more suitable intermediate ( N 2 -CBZ-TDTP-Me) for the synthesis of new glycopeptides.