Philippe Bisseret

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.

Novel bacterial triterpenoids of the hopane series from Nitrosomonas europaea and their significance for the formation of the C35 bacteriohopane skeleton

Abstract In addition to aminobacteriohopanetriol and adenosylhopane, three new hopanoids were isolated from the bacterium Nitrosomonas europaea: two N-acylaminobacteriohopanetriols, a hopanoid presenting a carbon carbon bond between ribonolactone and hopane and related to a putative intermediate involved in the formation of the C35 bacteriohopane skeleton and finally a condensation product between aminobacteriohopanetriol and trinorbacteriohopan-32-al, an artifact resulting from the autoxidation of the aminotriol.

Abiotic and biological hopanoid transformation : towards the formation of molecular fossils of the hopane series

Abstract Tritium labeled hopane and bacteriohopane were incubated in the presence of the bacterium Arthrobacter simplex . In both experiments, the corresponding 17(21)-olefins and 17,21-epoxides were formed from the saturated hydrocarbon. In addition, hop-17(21)-en-20-one, 17,21-secohopane-17,21-dione and trinorhopan-21-one were found in the case of the hopane incubation. Control experiments were performed in the absence of the bacteria either with the culture medium alone or with the culture medium containing the non-ionic surfactant Emulphogene®. Tritium labeled hop-17(21)-ene and 17,21-epoxyhopane were incubated under the same conditions. Only the 17(21)-olefins and probably to some extent the 17,21-epoxides, resulted from the bioconversion of the corresponding saturated hopanoids. The other hopanoids were formed by the abiotic oxidation of hop-17(21)-ene. Their formation was however favored by the presence of the bacteria or of the non-ionic surfactant Emulphogene®, suggesting that dispersion of the hydrophobic hopanoid in the aqueous phase was essential for the oxidative degradation. Surprisingly, no degradation of the n -alkyl chain of bacteriohopane was observed.

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.

Relative configurations of carbapseudopentose moieties of hopanoids of the bacterium Zymomonas mobilis and the cyanobacterium ‘Anacystis montana’

Abstract A bacteriohopanetetrol cyclitol ether with a new configuration of its carbapseudopentose moiety has been isolated from the cyanobacteriu, ‘ Anacystis montana ’ and compared to a similar hopanoid previously isolated from Zymomonas mobilis . As shown by two dimensional 1 H-NMR spectroscopy using Nuclear Overhauser Effect correlations, both compounds were diastereomers and differed from a third stereomer found in the biphytanyl lipids of the thermoacidophilic archaebacterium Sulfolobus sp.

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.

Inverse Electron-Demand [4 + 2]-Cycloadditions of Ynamides: Access to Novel Pyridine Scaffolds

Functionalized polycyclic aminopyridines are central to the chemical sciences, but their syntheses are still hampered by a number of shortcomings. These nitrogenated heterocycles can be efficiently prepared by an intramolecular inverse electron demand hetero Diels-Alder (ihDA) cycloaddition of ynamides to pyrimidines. This ihDA/rDA sequence is general in scope and affords expedient access to novel types of aminopyridinyl scaffolds that hold great promise in terms of exit vector patterns.

Stereodivergent Hydrogermylations of α‑Trifluoromethylated Alkynes and Their Applications in Cross-Coupling Reactions

The hydrometalation of alkynes with group 14 elements such as tin- or silyl hydrides is a classical transformation in organic synthesis. Strangely, among the group 14 elements, the use of germanium hydrides is rarely seen. Two efficient, stereodivergent, and broadly applicable routes to (Z)- and (E)-α-CF3-vinylgermanes by regio- and stereoselective hydrogermylation of α-trifluoromethylated alkynes under radical or transition-metal-catalyzed conditions are reported. Furthermore, we demonstrate that the resulting stereodefined fluorinated building blocks are remarkable cross-coupling partners, provided that the vinylgermane is appropriately tuned electronically, as demonstrated by the synthesis of trisubstituted (Z)- and (E)-α-trifluoromethylated alkenes.

Bromine, N-bromosuccinimide and sulphur induced isomerizations in the hopane series

Abstract When reacted with bromine, N-bromosuccinimide or molten sulphur, triterpenoids of the 17β(H),21β(H)-hopane series were converted into their 17α(H),21β(H) and 17β(H),21α(H) isomers of geochemical significance.

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.