Premium
Synthesis of 1‐ C ‐Glycoside‐Linked Lipid II Analogues Toward Bacterial Transglycosylase Inhibition
Author(s) -
Lin ChengKun,
Chen KuoTing,
Hu ChiaMing,
Yun WenYi,
Cheng WeiChieh
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406629
Subject(s) - moiety , disaccharide , lipid ii , chemistry , phosphonate , stereochemistry , glycoside , lipid a , pyrophosphate , glycosyltransferase , biochemistry , biosynthesis , enzyme , bacteria , biology , genetics
Preparation of Lipid II analogues containing an enzymatically uncleavable 1‐ C ‐glycoside linkage between the disaccharide moiety and the pyrophosphate‐ or pyrophosphonate‐lipid moiety is described. The synthesis of a common 1‐ C ‐vinyl disaccharide intermediate has been developed that allows easy preparation of both an elongated sugar‐phosphate bond and a sugar‐phosphonate moiety, which are coupled with the polyprenyl phosphate to give the desired molecules. Inhibition studies show how a subtle structural modification results in dramatically different potency toward bacterial transglycosylase (TGase), and the results identify Lipid II‐C‐O‐PP (IC 50 =25 μ M ) as a potential TGase inhibitor.