119879-79-7Relevant academic research and scientific papers
Synthesis of modified peptidoglycan precursor analogues for the inhibition of glycosyltransferase
Dumbre, Shrinivas,Derouaux, Adeline,Lescrinier, Eveline,Piette, Andre,Joris, Bernard,Terrak, Mohammed,Herdewijn, Piet
supporting information; experimental part, p. 9343 - 9351 (2012/07/14)
The peptidoglycan glycosyltransferases (GTs) are essential enzymes that catalyze the polymerization of glycan chains of the bacterial cell wall from lipid II and thus constitute a validated antibacterial target. Their enzymatic cavity is composed of a donor site for the growing glycan chain (where the inhibitor moenomycin binds) and an acceptor site for lipid II substrate. In order to find lead inhibitors able to fill this large active site, we have synthesized a series of substrate analogues of lipid I and lipid II with variations in the lipid, the pyrophosphate, and the peptide moieties and evaluated their biological effect on the GT activity of E. coli PBP1b and their antibacterial potential. We found several compounds able to inhibit the GT activity in vitro and cause growth defect in Bacillus subtilis. The more active was C16-phosphoglycerate-MurNAc-(l-Ala-d-Glu)-GlcNAc, which also showed antibacterial activity. These molecules are promising leads for the design of new antibacterial GT inhibitors.
Regiospecific Opening of Glycidyl Derivatives Mediated by Boron Trifluoride. Asymmetric Synthesis of Ether-Linked Phospholipids
Guivisdalsky, Pedro N.,Bittman, Robert
, p. 4637 - 4642 (2007/10/02)
A short, chiral synthesis of unnatural, cytotoxic ether-linked phospholipids is reported in which the key step is the very high regio- and stereospecific nucleophilic opening of the p-toluenesulfonate (1a, 1b) or tert-butyldiphenylsilyl ether (6a, 6b) derivatives of (R)- or (S)-glycidol with 1-hexadecanol using boron trifluoride etherate as catalyst.The enantiomeric excess of the ring-opened products was >94percent, as judged by 1H NMR and chiral HPLC analysis of the Mosher ester derivatives, indicating that ring opening of 1 and 6 proceeds without significant loss of optical purity.The synthetic strategy of using optically active glycidyl derivatives as the precursor of the glycerol backbone permits the desired enantiomers of 1(3)-O-2-O-methylphosphocholines (5a, 5b) to be generated in good yield and high optical purity from the ring-opened intermediates (2, 7) in three steps without the use of protecting groups.
