Rapid assembly of the polyhydroxylated b-amino acid constituents of microsclerodermins C, D et E.

A very short and efficient synthesis of protected derivatives of APTO and AETD, the complex polyhydroxylated -amino acid residues present in microsclerodermins C, D, and E, is described. The targets are obtained in only five steps, in 23% and 16% overall yields, respectively. The key transformation involves the completely diastereoselective two-carbon homologation of appropriately selected intermediate chiral sulfinimine

Effect of capping groups at the N- and C-termini on the conformational preference of α,β-peptoids

invitation, special theme issue on Foldamer ChemistryInternational audienc

Enzymatic basis of "hybridity" in thiomarinol biosynthesis

Thiomarinol is a naturally occurring double-headed antibiotic that is highly potent against methicillin-resistant Staphylococcus aureus. Its structure comprises two antimicrobial subcomponents, pseudomonic acid analogue and holothin, linked by an amide bond. TmlU was thought to be the sole enzyme responsible for this amide-bond formation. In contrast to this idea, we show that TmlU acts as a CoA ligase that activates pseudomonic acid as a thioester that is processed by the acetyltransferase HolE to catalyze the amidation. TmlU prefers complex acyl acids as substrates, whereas HolE is relatively promiscuous, accepting a range of acyl-CoA and amine substrates. Our results provide detailed biochemical information on thiomarinol biosynthesis, and evolutionary insight regarding how the pseudomonic acid and holothin pathways converge to generate this potent hybrid antibiotic. This work also demonstrates the potential of TmlU/HolE enzymes as engineering tools to generate new "hybrid" molecules. The biosynthetic mechanism responsible for generating the antibiotic thiomarinol was elucidated. In contrast to previous hypotheses, TmlU acts as a CoA-ligase and works in tandem with a second enzyme, acyltransferase HolE, to link two antimicrobial warheads pseudomonic acid and holothin, creating a hybrid antibiotic (see scheme)

Vers la synthèse totale de microsclerodermine D

Poste

Vers la synthèse totale de microsclerodermine D

Poste

Enantioselective synthesis of (+)-d-coniceine by reductive photocyclisation of a dienamide

Poste

alpha, beta peptoïdes : synthèse, étude et application

Communication oral

Greener peptoid synthesis in additive-free water-based media

International audienceHighly efficient procedures were developed for greener synthesis of sequence-defined peptoid oligomers. The optimised chain elongation procedure is carried out in water-based media in a unique N to C direction, and comprises a convenient one-pot two-step deprotection/coupling sequence for the installation of each new peptoid residue. The process is so efficient that the only work-up procedure required after each intermediate coupling step is aqueous extraction. In stark contrast to the traditional procedures, the only solvents apart from water used during the synthesis and workup processes are EtOH, MeOH or EtOAc. Furthermore, there is no requirement for specialised water-soluble protecting groups or inclusion of additives apart from the reagents in the reaction media