The conformation in CDCl of the synthetic 4-epimer of the fatural synergimycin factor B (Virginiamacin S ) has been obtained from 2D H NMR spectroscopic data using NOE and differeht COSY techniques. The characteristics of the three NH protons have also been determined (temperature shift dependence, dilution and deuterium exchange).Conformations of the two diastereomeric depsipeptides are strikingly similar with respect to the backbone and cis/trans peptide bond configurations. This results for VS-epi4 in a rather unexpected type of p bend for the 13-61 sequence, reinforced by the same intramolecular hydrogen bridge bonding mechanism [Pro3C0 --f NHPhg"1 as for the natural isomer. The aromatic side chain of P-MePhe' however stacks over the preceding Pro3-residue instead of over the succeeding 4-0xo-Pec' as is the case in VS . The outer surface of the 2-5 region remains pronouncedly lipophilic. be reater in VS-epi4. Some other orientational differences may reside in the 95-11-region e.g . at NH(Thrl-) and the carbonyl grouping of the 4-0x0-Pec' residue.The conformational mobility of the cyclic residues seems to I " . Virginiamycin S (VS) constitutes the B factor of pairwise acting synergistic antibiotica of the synergimycin family produced by Stremtomyces Virgineae. Concomitantly with the A factor (VM), it irreversibly blocks the process of cell multiplication and protein synthesis (1, 2 ) and the mode of action at the ribosomic level is currently the subject of intense studies (3).The preparation of the MePhe' epimer ( 2 ) of the native VS1 (1) has recently been reported from these laboratories (4). VS-epi4 was obtained by re-cyclization of the opened linear peptide lactone called VS-seco (1) after strong activation of the latter (4, 5), whereby partial epimerization was inevitable (6). Bio assays have shown (7) that VS-epi4 does not bind to ribosomes. The present study was undertaken with the aim to unravel the conformational behaviour in solution in order to verify if dramatic changes in the spatial structurization had occured as to eventually explain its non-activity.
ChemInform Abstract Mutalomycin is a metal-complexing antibiotic. Two-dimensional NMR techniques are used for the complete assignment of the 1H spectrum of its sodium salt (I). The hydrogen bond between the carboxylate anion and the hydroxyl group at C-29 stabilizes the pseudo-cyclic arrangement of (I).
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