Ma, NianchunJia, YanxingLiu, ZuoshengGonzalez-Zamora, EduardoBois-Choussy, MicheleMalabarba, AdrianoBrunati, CristinaZhu, Jieping2010-11-252010-11-252010-11-25200510.1016/j.bmcl.2004.11.014https://infoscience.epfl.ch/handle/20.500.14299/58461A modified vancomycin binding pocket (D-O-E ring) incorporating a CHNHCOR function at the AA4 position is designed and synthesized. Potent bioactivities against both sensitive- and resistant-strain are found for some of these compds. (MIC 4 micro g/mL against VREF). From this preliminary SAR studies, it was speculated that the D-Ala-D-Ala binding was required for this series of compds. since the corresponding des-leucine deriv. is inactive. The presence of long aliph. chain was important for the desired activities and such hydrophobic effect is specific as no beneficial effect is obsd. when the same aliph. chain was attached to the other part of the mol. [on SciFinder (R)]Chirality (axial; synthesis of macrocyclic glycopeptides with axial chirality via thermal atropoisomerization); Structure-activity relationship (bactericidal; synthesis via SNAr-based macrocyclization and glycosylation and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Etherification (cyclo; synthesis by glycosylation of parent 16-membered biaryl ether and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Reduction; Substitution reaction (synthesis by azide redn. followed by SNAr-based macrocyclization via biaryl ethers and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Glycosylation (synthesis by glycosylation of parent 16-membered biaryl ether and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Antibiotics; Staphylococcus aureus (synthesis via SNAr-based macrocyclization and glycosylation and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Heterocyclic compounds; Macrocyclic compounds Role: PAC (Pharmacological activity)RCT (Reactant)SPN (Synthetic preparation)BIOL (Biological study)PREP (Preparation)RACT (Reactant or reagent) (synthesis via SNAr-based macrocyclization and glycosylation and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Glycopeptides Role: PAC (Pharmacological activity)SPN (Synthetic preparation)BIOL (Biological study)PREP (Preparation) (synthesis via SNAr-based macrocyclization and glycosylation and structure-activity relationship against vancomycin-resistant enterococci of macrocyclic glycopeptides); Isomerization (thermalthermal atropoisomerization; synthesis of macrocyclic glycopeptides with axial chirality via thermal atropoisomerization)macrocyclic glycopeptide synthesis antibiotic vancomycin resistant enterococci; vancomycin glycopeptide structure activity antibiotic axial chirality; azide redn cycloetherification nucleophilic substitution thermal atropoisomerization glycosylationtext::journal::journal article::research article