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A vinylogous cephalosporine bearing a dihydroxythiophene moiety as a potential catechol surrogate has been synthesised ( I-e Download : Download high-res image (58KB) Download : Download full-size image Figure 1 . -β). Even if the anti staphylococcus spectrum displayed by this compound is of interest, its activity against Pseudomonas species, expected for such a structure, remains disappointing.

As part of an effort to discover novel antibacterial agents, a new and efficient synthesis was established in order to provide a large amount of UDP-N-acetylmuramic acid (UDP-MurNAc).

The O -β- d -ribofuranosyl nucleoside I is the minimal structural entity of liposidomycins maintaining enzyme inhibitory activity. Modifications performed on both the primary amine and the uracil moieties clearly demonstrate their major contribution to the inhibition of the bacterial translocase (MraY).

O-beta-D-ribofuranosyl nucleoside I is the minimal structural entity of liposidomycins that maintains enzyme inhibitory activity on MraY. A set of compounds with hydroxyl patterns different from I has been synthesized. The presence of a hydroxyl group in the 3" position is essential for the activity. The 3'-deoxy derivative (IV), however, shows a 5-fold improved potency.

The synthesis and inhibitory activity against MraY of a series of simplified analogues of liposidomycins are described. These compounds were mainly obtained by performing parallel synthesis in the 6′-position of a scaffold that gathers key features found necessary for the binding to MraY. Thus, inhibitory activity was improved from 5300 to 140 nM. This improvement was correlated with the length and lipophilicity of substituents, but was found to be independent of the nature of the chemical bond generated. In addition, some of these inhibitors presented encouraging antibacterial activities.

Enantioselective synthesis of the isocephem synthon 2 has been carried out by assembling 3 building blocks. Cycloaddition of phthalimido acetyl chloride with a chiral imine gave the β-lactam nucleus in 80% diastereoisomeric excess (d.e.). The elaboration of the thiazine ring was carried out using a highly functionalised epoxy ester 12 and P2I4 mediated water elimination.