Claude Taillefumier

The click triazolium peptoid side chain: a strong cis-amide inducer enabling chemical diversity.

Access to homogeneous and discrete folded peptoid structures primarily depends on control of the cis/trans isomerism of backbone tertiary amides. This can be achieved by designing specific side chains capable of forming local interactions with the backbone. This is often undertaken at the expense of side-chain diversity, which is a key advantage of peptoids over other families of peptidomimetics. We report for the first time a positively charged triazolium-type side chain that does not compromise diversity and exhibits the best ability reported to date for inducing the cis conformation. The cis-directing effect was studied in N-acetamide dipeptoid model systems and evaluated in terms of K(cis/trans) using NMR spectroscopy in aprotic and protic solvents. Computational geometry optimization and natural bond orbital analysis in combination with NOESY experiments were consistent with a model in which n → π*(Ar) electronic delocalization [from carbonyl (O(i-1)) to the antibonding orbital (π*) of the triazolium motif on residue i] may be operative. In the computational model (gas-phase) and experimentally in CDCl(3), H-bonding between the triazolium C-H proton and the C(i)═O(i) oxygen was also identified and may act cooperatively with the n → π*(Ar) delocalization, resulting in the absence of the trans rotamers in CDCl(3).

Convenient Solution-Phase Synthesis and Conformational Studies of Novel Linear and Cyclic α,β-Alternating Peptoids

The synthesis of a novel family of peptidomimetics composed of linear and cyclic alpha,beta-alternating peptoids is described. Oligomers consisting of up to six peptoid residues (n = 1-3) were synthesized on large scale with use of an efficient iterative solution-phase method and longer oligomers (n = 4, 5) were obtained by the coupling of appropriately protected shorter oligomers. Preliminary conformational studies of these hybrid peptoids are reported.

The tert-butyl side chain: a powerful means to lock peptoid amide bonds in the cis conformation.

The very simple sterically hindered tert-butyl side chain exerts complete control over the peptoid amide geometry which only exists in the cis conformation. It is exemplified in NtBu glycine homo-oligomers and in linear oligopeptoids designed with an alternating cis-trans backbone amide pattern.

Efficient conditions for the synthesis of C-glycosylidene derivatives: a direct and stereoselective route to C-glycosyl compounds

Abstract Efficient conditions for the synthesis of C -glycosylidene compounds from lactones based on Wittig reactions of cyanomethyl triphenylphosphoranylidene involving microwave heating are described: subsequent stereoselective reduction of the anomeric olefins gave the corresponding C -glycosides in good yields with high stereocontrol.

Synthesis and Solution Conformation of Homo-β-peptides Consisting of N-Mannofuranosyl-3-ulosonic acids

The synthesis and solution conformation of homo-oligomers of beta-aminoacids, beta-N-mannofuranosyl-3-ulosonic acids, have been studied by NMR, MD simulation, and circular dichroism. These oligomers feature a spirocyclic disubstitution and a N,O-acetal functionality at the beta-carbon of the backbone, an unprecedented situation in the realm of beta-peptides. Our study shows that tetramer 10 and hexamer 11 adopt a characteristic secondary structure. In the hexamer 11, NMR investigations coupled with MD simulations suggest the preference for a double C(8) turn forming conformation.

Facile synthesis of fused furanosyl β-amino acids from protected sugar lactones: incorporation into a peptide chain

Abstract The synthesis of fused furanosyl β-amino esters from protected sugar lactones is described, using the combination of a Wittig type reaction and 1,4-addition of benzylamine on the resulting glycosylidenes. This sequence of reactions afford either N-glycosyl-3-ulosonic acid esters, which are the β-analogues of anomeric sugar α-amino esters, or open-chain sugar β-enamino esters, when a retro-Michael reaction takes place after addition of benzylamine. Incorporation of the fused furanosyl β-amino ester 2a into a peptide chain is also described.

Synthesis and biological testings as inhibitors of HMGCoA reductase of the seco-acid of tuckolide and its C-7 epimer

The seco-acid of the natural macrolactone, tuckolide (decarestrictin D) and the C-7 epimer have been prepared in enantiomerically pure form from D-gluconolactone and poly(3-hydroxy butyric acid). The key steps are Horner Emmons olefination and stereoselective reduction of the resulting enone to provide both epimers at C-7. None of the seco-acids inhibit microsomal HMGCoA reductase of pea or rat liver. It may be concluded that the cholesterol biosynthesis inhibiting effect of tuckolide is unlikely to proceed via HMGCoA reductase inhibition.

An efficient route to acyclic C-nucleosides and fused-ring analogues of uridine from exo-glycals.

Beta-amino esters prepared from activated exo-glycals are transformed into acyclic C-nucleoside with a C-4-substituted uracil derivative that can be cyclized under Mitsunobu conditions to provide a new family of fused-ring analogues of uridine nucleoside in which the N-1 nitrogen atom is embedded in an imino sugar ring. An analogue of uridine of D-ribo configuration is prepared.

Facile dibromoolefination of lactones using bromomethylenetriphenylphosphorane

Dibromoolefination of lactones was achieved in high yields using bromomethylenetriphenylphosphorane in refluxing tetrahydrofuran. This reaction is believed to proceed via bromination of the monobromophosphorane from the corresponding bromomethyltriphenylphosphonium bromide with concomitant formation of methylenetriphenylphosphorane as shown by 31P NMR. Transylidation should occur to afford the reactive dibromomethylenetriphenylphosphorane.

Immobilization of proteases on chitosan for the development of films with anti-biofilm properties

Bacterial resistance due to biofilm formation-particularly Staphylococci biofilms-is associated with multiple problems in medical settings where biofilms can colonize medical indwelling devices and cause nosocomial infections. It was against this backdrop that we explored the anti-biofilm activities of a set of proteases against biofilm formation by Staphylococcus aureus, Listeria monocytogenes and Pseudomonas aeruginosa. The selected screened enzymes were immobilized on chitosan to obtain films with anti-biofilm activities. Immobilization efficiency was about 94% for protease from Bacillus licheniformis and reached up to 96% for Neutrase. In vitro assays performed in brain heart infusion (BHI) broth using the Biofilm Ring Test highlighted that immobilized enzymes were efficient against biofilms of Staphylococci cultures, especially protease from B. licheniformis and Neutrase from Bacillus amyloliquefaciens.