Jacques Eustache

Inhibition of aryl acid adenylation domains involved in bacterial siderophore synthesis

Aryl acid adenylation domains are the initial enzymes for aryl‐capping of catecholic siderophores in a plethora of microorganisms. In order to overcome the problem of iron acquisition in host organisms, siderophore biosynthesis is decisive for virulence development in numerous important human and animal pathogens. Recently, it was shown that growth of Mycobacterium tuberculosis and Yersinia pestis can be inhibited in an iron‐dependent manner using the arylic acyl adenylate analogue 5′‐O‐[N‐(salicyl)‐sulfamoyl] adenosine that acts on the salicylate activating domains, MbtA and YbtE [Ferreras JA, Ryu JS, Di Lello F, Tan DS, Quadri LEN (2005) Nat Chem Biol1, 29–32]. The present study explores the behaviour of the 2,3‐dihydroxybenzoate activating domain DhbE (bacillibactin synthesis) and compares it to that of YbtE (yersiniabactin synthesis) upon enzymatic inhibition using a set of newly synthesized aryl sulfamoyl adenosine derivatives. The obtained results underline the highly specific mode of inhibition for both aryl acid activating domains in accordance with their natively accepted aryl moiety. These findings are discussed regarding the structure–function based aspect of aryl substrate binding to the DhbE and YbtE active sites.

Ring closing metathesis as an efficient approach to branched cyclitols and aminocyclitols: a short synthesis of valiolamine

Abstract Ring closing metathesis of sugar-derived 1,6 dienes is the key step for the construction of highly functionnalized cyclohexenes, precursors of branched cyclitols and aminocyclitols. The method has been used for a short synthesis of valiolamine.

A Diverted Total Synthesis of Mycolactone Analogues: An Insight into Buruli Ulcer Toxins

Mycolactones are complex macrolides responsible for a severe necrotizing skin disease called Buruli ulcer. Deciphering their functional interactions is of fundamental importance for the understanding, and ultimately, the control of this devastating mycobacterial infection. We report herein a diverted total synthesis approach of mycolactones analogues and provide the first insights into their structure-activity relationship based on cytopathic assays on L929 fibroblasts. The lowest concentration inducing a cytopathic effect was determined for selected analogues, allowing a clear picture to emerge by comparison with the natural toxins.

Stereoselective synthesis of arabinose-derived phosphonates

Abstract A short, stereoselective synthesis of three new azasugar-derived phosphonates is described. The new compounds are versatile intermediates for the synthesis of glycosyltransferase inhibitors.

Formation of dissymmetric eight-membered silalketals by ring-closing metathesis and their conversion to spiroketals

Eight-membered unsymmetrical silalketals are formed by RCM of mixed allyl/homoallyl silalketals. They are crucial intermediates in a short synthetic sequence to spiroketals illustrated in this paper by the synthesis of the C28–C38 portion of okadaic acid.

A new concise synthesis of nectrisine and its facile conversion to phosphonoazasugars

Abstract The synthesis of new sugar-derived phosphonic acids from protected nectrisine is described. The key step is a highly stereoselective addition of a phosphonate anion to a sugar-derived dihydropyrrole to provide a versatile synthetic intermediate which can be functionalised in multiple ways.

Ring closing metathesis of sterically hindered 1,6 - dienes: A new approach to 5-membered branched cyclitols

Abstract A sterically hindered 1,6-dienic system underwent clean ring-closing metathesis using Schrocks catalyst. The product was converted into new 5-membered branched cyclitols and is a potential precursor of other biologically relevant aminocyclitols.

Electrophilic selenocyclization in 2-ene-1,5-diol systems: unexpected oxetane vs. tetrahydrofuran formation

Electrophile-induced cyclization of (E)- and (Z)-2-ene-1,5-diols to tetrahydrofurans and oxetanes is described. Significant differences between the present report and previous work have been noted. A tentative model is proposed.

Cyclic phosphonomethylphosphinates: a new type of phosphorus-containing sugars

Abstract The first synthesis of arabino -configured cyclic phosphonomethylphosphinates is described. The key step is the condensation of the triethylester of H -phosphinylphosphonate 10 on an hydroxyaldehyde 11 derived from a d -arabinal derivative followed by a cyclization induced under acetylation conditions.

H-Phosphonylphosphonate triethylester: the first member of a novel family of stable bisphosphorylated compounds; its short synthesis and reactivity with aldehydes

Abstract A short preparation of the first member ( 1 ) of the novel H-phosphonylphosphonate family is described. Its reaction with aldehydes provides a straightforward access to the hitherto almost unprecedented class of α-hydroxyphosphinylphosphonates 3 of potential value in particular in medicinal chemistry.