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.

We report a novel, very mild, highly stereoselective preparation of 2-arylvinylphosphonates at room temperature that involves the copper iodide-mediated cross-coupling of H-phosphonates with vinyliodonium tetrafluoroborates.

From diplopterol to tetrahymanone: A simple chemical transformation from the hopane series to the gammacerane series. Amongst all triterpenoids, the hopane and gammacerane series are closely related both from a biosynthetic as well as from a structural point of view. Substances from both classes are used by geochemists as specific biomarkers for organisms producing them. We present here a process allowing for the first time the transformation of diplopterol of the hopane series into tetrahymanone of the gammacerane series. Each step has been optimised and the characterisation of the main secondary products has been performed.

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We report a new flexible method for the synthesis of 2-functionalized benzo[b]furans and indoles from readily available o-(2,2-dibromovinyl)-phenol, -aniline or -acetanilide using a tandem Pd-assisted cyclization-coupling reaction. (C) 2003 Elsevier Ltd. All rights reserved.

Treatment of carbohydrate-derived γ-hydroxyphosphonic acids under usual acetylation conditions affords the corresponding phostones in good yield. The method could be used for the preparation of free phostones as well as α- and β-phosphonomethylarabinose.

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.

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.

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.

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.

[GRAPHICS]Stereoselective preparation of a new arabinose-derived aziridine and functionalization of the corresponding N-BH3 complex are described. Regio- and stereoselective aspects are discussed.

In addition to aminobacteriohopanetriol and adenosylhopane, three new hopanoids were isolated from the bacterium Nitrosomonas europaea: two N-acylaminobacteriohopanetriols, a hopanoid presenting a carboncarbon 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.

A short, stereoselective synthesis of three new azasugar-derived phosphonates is described. The new compounds are versatile intermediates for the synthesis of glycosyltransferase inhibitors. (C) 1998 Elsevier Science Ltd. All rights reserved.

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 1H-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.

Cells of the bacterium Acetobacter xylinum were analysed for their residual triterpenoid content after exhaustive lipid extraction using chloroform/methanol. Whereas the well known bacteriohopanetetrol mixture was present in the extract, the cells still contained a single bacteriohopanepentol cyclitol ether which could be detected either as the primary alcohol derivative after H5IO6 oxidation followed by NaBH4 reduction of the already extracted cells or as the octa-acetate by direct acetylation followed by solvent extraction. This is the first evidence of a probable selective complexation of a hopanoid via non-covalent linkages to other cell constituents.

In the presence of cuprous chloride, the representative biohopanoid 1a was smoothly converted by oxidation in pyridine into aldehydes, ketones and carboxylic acids with the same skeletons as those of molecular fossils ubiquitously found in the organic matter of sediments.

On heating in liquid sulphur, the unsaturated hopanoid hop-17(21)-ene 1 was converted to a major extent into the series of organo-sulphur products 5–9, all interest as potential sedimentary biomarkers.

Triterpenoids of the hopane series are frequently found as membrane stabilizers in Eubacteria. Owing to their usually high intracellular concentration and their stability, hopanoids are better suited for the elucidation of the isoprenoid biosynthetic routes in bacteria than the more wide-spread polyprenol derivatives (bactoprenol, ubiquinones and menaquinones) or carotenoids. Incorporations of C-13 labelled precursors (acetate, glucose, pyruvate and D-erythrose) into hopanoids and bacterial ubiquinones allowed the discovery and partial elucidation of a novel biosynthetic pathway for the early steps of isoprenoid biosynthesis leading to IPP in bacteria. The resulting hypothetical biogenetic scheme excludes HMG CoA and mevalonate as precursors and includes direct formation of the C-5 isoprenic skeleton i) by condensation of a C-2 subunit derived from pyruvate decarboxylation on the C-2 carbonyl group of a triose phosphate derivative and ii) a transposition step. This peculiar feature combined with other specific aspects linked to the formation of bacterial hopanoids (lack of specificity of squalene cyclase, formation of the amphiphilic C-35 bacteriohopane skeleton by a carbon/carbon linkage between a D-pentose and a triterpene, unusual methylations) points out the diversity of the routes employed by living organisms to obtain their membrane constituents.