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As part of our continuing effort to discover new potential anti-inflammatory agents, four new triterpenoids, chisopanins L-O (1-4), were isolated from the twigs of Chisocheton paniculatus. Their structures were established on the basis of detailed analysis of spectroscopic data, including IR, NMR (1D and 2D NMR), and HR-ESI-MS. Their inhibitory effects against nitric oxide (NO) production were evaluated in an in vitro model of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Compounds 1, 3, and 4 were found to exhibit moderate activity with [IC.sub.50] values less than 10 µmol/L. Key words: Chisocheton paniculatus, triterpenoids, anti-inflammatory activity. Dans le cadre de nos travaux effectues dans le but de decouvrir de nouveaux agents potentiellement anti-inflammatoires, on a isole quatre nouveaux triterpenoides, les chisopanines L-O (1-4) des brindilles de Chisocheton paniculatus. On a determine leurs structures en se basant sur une analyse detaillee de donnees spectroscopiques, dont l'infrarouge, la resonance magnetique nucleaire uni- (RMN 1D) et bi-dimensionnelle (RMN 2D) et la spectrometrie de masse avec ionisation par electronebulisation et a haute resolution (SM-IEN-HR). On a evalue leurs effets d'inhibition contre la production d'oxyde nitrique (NO) dans un modele in vitro de macrophages RAW264,7 stimules par un lipopolysaccharide (LPS). Les composes 1, 3 et 4 presentent une activite moderee avec des valeurs de [IC.sub.50] inferieures a 10 µmol/L. Mots-cles : Chisocheton paniculatus, triterpenoi'des, activite anti-inflammatoire. [Traduit par la Redaction], Introduction Chisocheton paniculatus Hiern (Meliaceae) is a rich source of protolimonoids and simple limonoids. (1,2) Several new C-seco-type tetranortriterpenoids and protolimonoids were isolated from this plant, showing significant anti-inflammatory activity [...]

We have investigated the mechanism of action of Aquifex aeolicus IspH [E-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) reductase], together with its inhibition, using a combination of site-directed mutagenesis ([K.sub.M], [V.sub.max]), EPR and [sup.1]H, [sup.2]H, [sup.13]C, [sup.31]P, and [sup.57]Fe-electron-nuclear double resonance (ENDOR) spectroscopy. On addition of HMBPP to an (unreactive) E126A IspH mutant, a reaction intermediate forms that has a very similar EPR spectrum to those seen previously with the HMBPP 'parent' molecules, ethylene and allyl alcohol, bound to a nitrogenase FeMo cofactor. The EPR spectrum is broadened on [sup.57]Fe labeling and there is no evidence for the formation of allyl radicals. When combined with ENDOR spectroscopy, the results indicate formation of an organometallic species with HMBPE a [pi]/[sigma] 'metallacycle' or [[eta].sup.2]-alkenyl complex. The complex is poised to interact with [H.sup.+] from E126 (and H124) in reduced wt IspH, resulting in loss of water and formation of an [[eta].sup.1]-allyl complex. After reduction, this forms an [[eta].sup.3]-allyl [pi]-complex (i.e. containing an allyl anion) that on protonation (at C2 or C4) results in product formation. We find that alkyne diphosphates (such as propargyl diphosphate) are potent IspH inhibitors and likewise form metallacycle complexes, as evidenced by [sup.1]H, [sup.2]H, and [sup.13]C ENDOR, where hyperfine couplings of approximately 6 MHz for [sup.13]C and 10 MHz for [sup.1]H, are observed. Overall, the results are of broad general interest because they provide new insights into IspH catalysis and inhibition, involving organometailic species, and may be applicable to other [Fe.sup.4][S.sup.4]-containing proteins, such as IspG. enzyme inhibition | iron-sulfur protein | isoprenoid biosynthesis | nonrnevalonate pathway www.pnas.org/cgi/doi/10.1073/pnas.0911087107

The convergent construction of the tetracyclic triterpenoids cucurbitacins B and C are presented. The diastereomer of the core of the cucurbitacins, epimeric at C8, C9 and C10 is prepared through a highly regio- and stereoselective Diels-Alder reaction of the diene and the novel dienophile.

A concise, biomimetic total synthesis of the terpenoid skeleton (+)-chabraol is achieved via 6 steps from the chiral epoxide, which has involved an intramolecular Prins double cyclization to produce the bicycle[2.2.1] core of the natural product as the major step. The absolute configuration of natural chabranol is designated through the first asymmetric total synthesis.

The X-ray crystal structure characterization of recombinant epi-isozizaene synthase (EIZS), a sesquiterpene cyclase from Streptomyces coelicolor A3(2) is described. Comparison of EIZS and D99N EIZS provides insight into the conformational changes required for the substrate binding and catalysis in a bacterial terpenoid cyclase and the binding interactions of benzyltriethylammonium cation (BTAC) which might imitate those of a carbocation intermediate in catalysis.

The article demonstrates the applicability of the IspG enzyme for the synthesis of the (E)-4-hydroxy-3-methylbut-2-enyl diphosphate intermediate. IspG is shown to act as an important enzyme in the isoprenoid biosynthesis observed in bacteria, parasites and plants.

[super 57]Fe Mossbauer spectroscopy is used for examining the LytB cluster in whole Escherichia coli cells and in the anaerobically purified enzyme. The studies have shown that in LytB [[4Fe-4S].sup.2+] cluster is attached to the protein by three conserved cysteines and contains a hexacoordinated iron linked to three sulfurs of the cluster and three additional oxygen or nitrogen ligands.

The total sythesis and structural revision of the neurotrophic diterpenoids, tricholomalides A and B which was originally misassigned is reported. The key transformation in the synthesis includes a ketene [2+2] cycloaddition and a Gridnard-type reaction.