Total syntheses and initial evaluation of [Ψ[C(═S)NH]Tpg⁴]vancomycin, [Ψ[C(═NH)NH]Tpg⁴]vancomycin, [Ψ[CH₂NH]Tpg⁴]vancomycin, and their (4-chlorobiphenyl)methyl derivatives: synergistic binding pocket and peripheral modifications for the glycopeptide antibiotics.

ABSTRACT: Full details of studies are disclosed on the total syntheses of binding pocket analogues of vancomycin bearing the peripheral L-vancosaminyl-1,2-D-glucosyl disaccharide that contain changes to a key single atom in the residue-4 amide (residue-4 carbonyl O → S, NH, H2) designed to directly address the underlying molecular basis of resistance to vancomycin. Also disclosed are studies piloting the late-stage transformations conducted on the synthetically more accessible C-terminus hydroxymethyl aglycon derivatives and full details of the peripheral chlorobiphenyl functionalization of all of the binding-pocket-modified vancomycin analogues designed for dual D-Ala-D-Ala/D-Ala-D-Lac binding. Their collective assessment indicates that combined binding pocket and chlorobiphenyl peripherally modifi

SUBMITTER: Okano A 

PROVIDER: S-EPMC4376669 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature