Vancomycin: Structure and Transformation to CDP-I

Article abstract of DOI:10.1021/ja00361a029

The structure of vancomycin is assigned as 7 in which aspartate is present as asparagine, rather than isoasparagine (i.e., 4) as had been proposed previously (Williamson, M.P.; Williams, D.H.J.Am.Chem.Soc. 1981, 103, 6580).The mechanism of rearrangement of vancomycin to CDP-I has been investigated.The pathway is deduced: vancomycin -> succinimide 11 -> CDP-I-m (3) <*> CDP-I-M (2).Succinimide 11 has been isolated and characterized by FT-IR and FAB-MS; these data are in agreement with an in-chain succinimide but not a seco structure.Treatment of 11 at pH 8 leads to immediate appearance of the minor form of CDP-I, which slowly yields an equilibrium mixture with the major form (ca. 64:36 of 2:3).No major change in the equilibrium ratio or rate of equilibration was found by changing solvent (H2O, Me2SO, or 0.1percent TFA/20percent 2-propanol) or pH (in the range 2.0-8.0).High-field 1H NMR studies of 2 and 3 indicate that they are atropisomers involving different orientations of the Cl-substituted aromatic ring of residue 2, in agreement with earlier assignments by Williamson and Williams.It is concluded that 2 and 3 can interconvert by simple reorientation of the aromatic ring rather than via a transient cleavage product.The cyclophane ring in which the Cl-substituted aromatic residue 2 is embedded is enlarged by one methylene unit in the conversion of vancomycin to CDP-I; rotation of ring 2 can occur in CDP-I but not in vancomycin.The additional methylene unit in the N-terminal cyclophane ring of CDP-I causes the ring to lie in a conformation that is significantly different from that of vancomycin.