A review of methods to synthesise 4'-substituted nucleosides.

Modified nucleosides have received a great deal of attention from the scientific community, either for use as therapeutic agents, diagnostic tools, or as molecular probes. Perhaps the most difficult position of a nucleoside to modify is the 4'-position. Chemists have developed innovative methods to achieve this in a stereoselective manner to allow incorporation of a variety of functional groups.

Synthesis of spiropiperidine lactam acetyl-CoA carboxylase inhibitors.

The synthesis of 4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one-based acetyl-CoA carboxylase inhibitors is reported. The hitherto unknown N-2 tert-butyl pyrazolospirolactam core was synthesized from ethyl 3-amino-1H-pyrazole-4-carboxylate in a streamlined 10-step synthesis requiring only one chromatography procedure. The described synthetic strategy provides pyrazolo-fused spirolactams from halogenated benzylic arenes and cyclic carboxylates.

Inhibitors of phosphopantetheine adenylyltransferase.

Phosphopantetheine adenylyltransferase (PPAT) is an essential enzyme in Coenzyme A biosynthesis. Because bacterial PPAT and mammalian PPAT are dissimilar, this enzyme is an attractive antibacterial target. Based on the structure of the substrate, 4-phosphopantetheine, a dipeptide library was designed, synthesised and tested against Escherichia coli PPAT.

A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3[2H]-ones as inhibitors of chorismate synthase.

A series of 2(Z)-2-benzylidene-6,7-dihydroxybenzofuran-3[2H]-ones was identified as potent inhibitors of bacterial chorismate synthase. The 2'-hydroxy-4'-pentoxy analogue 33 is a potent inhibitor of Streptococcus pneumoniae chorismate synthase.

Antibacterial activity of synthetic analogues based on the disaccharide structure of moenomycin, an inhibitor of bacterial transglycosylase.

Moenomycin is a natural product glycolipid that inhibits the growth of a broad spectrum of Gram-positive bacteria. In Escherichia coli, moenomycin inhibits peptidoglycan synthesis at the transglycosylation stage, causes accumulation of cell-wall intermediates, and leads to lysis and cell death. However, unlike Esc.