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The petroleum ether extract of Iris domestica (Belamcanda chinensis) has been evaluated for activity against Trypanosoma brucei. Bioassay-guided fractionation led to the isolation of four known iridals as the active components. Chemical modification of these isolates afforded novel stable derivatives that maintained bioactivity. This is the first known report of the antitrypanosomal activity of these compounds.

Stereoselective cyclopropanation of a series of amino acid-derived enones to afford cyclopropyl keto-esters is reported, using a Michael-induced ring closure. The use of quinine and quinidine ether catalysts in the cyclopropanation step afforded the cyclopropyl keto-esters with high stereoselectivity. Results follow a consistent pattern, with the pseudoenantiomeric catalysts leading to opposite stereoselectivity, allowing for synthesis of either the syn or anti diastereomers.

SUMMARY Karenia brevis is a harmful marine dinoflagellate that forms yearly blooms in the Gulf of Mexico. Under normal growth conditions, K. brevis forms two predominant sterols (24R)-4α-methyl-5α-ergosta-8(14),22-dien-3β-ol (gymnodinosterol) and its 27-nor isomer (brevesterol). At the current time, there are no published studies concerning the biosynthesis of these two sterols. We have therefore undertaken experiments in which K. brevis was exposed to the fungicide fenpropidine, an inhibitor of the Δ14-reductase and the Δ87-isomerase that operate in sterol biosynthesis in both fungal and plant systems. Such exposure to fenpropidine has produced two, tri-unsaturated intermediates. The identifications of these two K. brevis sterol biosynthesis intermediates, via gas chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy techniques, were 4α-methyl-5α-ergosta-8,14,22-trien-3β-ol and 5α-ergosta-8,14,22-trien-3β-ol.

Etoposide is a widely prescribed anticancer agent that stabilizes topoisomerase II-mediated DNA strand breaks. The drug contains a polycyclic ring system (rings A-D), a glycosidic moiety at C4, and a pendant ring (E-ring) at C1. A recent study that focused on yeast topoisomerase II demonstrated that the H15 geminal protons of the etoposide A-ring, the H5 and H8 protons of the B-ring, and the H2', H6', 3'-methoxyl, and 5'-methoxyl protons of the E-ring contact topoisomerase II in the binary enzyme-drug complex [ Wilstermann et al. (2007) Biochemistry 46, 8217-8225 ]. No interactions with the C4 sugar were observed. The present study used DNA cleavage assays, saturation transfer difference [ (1)H] NMR spectroscopy, and enzyme-drug binding studies to further define interactions between etoposide and human topoisomerase IIalpha. Etoposide and three derivatives that lacked the C4 sugar were analyzed. Except for the sugar, 4'-demethyl epipodophyllotoxin is identical to etoposide, epipodophyllotoxin contains a 4'-methoxyl group on the E-ring, and 6,7- O, O-demethylenepipodophyllotoxin replaces the A-ring with a diol. Results suggest that etoposide-topoisomerase IIalpha binding is driven by interactions with the A- and B-rings and potentially by stacking interactions with the E-ring. We propose that the E-ring pocket on the enzyme is confined, because the addition of bulk to this ring adversely affects drug function. The A- and E-rings do not appear to contact DNA in the enzyme-drug-DNA complex. Conversely, the sugar moiety subtly alters DNA interactions. The identification of etoposide substituents that contact topoisomerase IIalpha in the binary complex has predictive value for drug behavior in the enzyme-etoposide-DNA complex.

Nitrocyclopropanation of amino-acid derived enones has led to a series of cyclopropyl peptidomimetics suitable for further elaboration to compounds with the potential for biological activity.

An efficient approach to novel cyclopropyl peptidomimetics has been developed. The synthetic route involves a cyclopropanation using ethyl (dimethylsulfuranylidene)acetate (EDSA) as the key step and affords a cyclopropyl peptidomimetic core in three steps from protected amino acid Weinreb amides.

Components previously reported from Cyclocarya paliurus include the oleananes cyclocaric acids A and B, with cyclocaric acid A possessing an oxetane ring. Isolation of cyclocaric acid A from the plant extract and comparison to the literature report show that the compound originally reported as cyclocaric acid A is, in fact, hederagenin. This was confirmed by independent synthesis of the oxetane and indicates that cyclocaric acid A may not actually be a natural product.

A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human topoisomerase IIα.

Two triterpenes were isolated using bioassay guided fractionation from the ethanol extract of Cyclocarya paliurus. Comparison to NMR spectra from a prior isolation reported in literature showed these two compounds to be previously reported Cyclocaric Acids A and B. However, after additional research into the oleanolic class of compounds, an independent synthesis of the reported Cyclocaric Acid A from hederagenin was completed. The conclusion is that the previously reported structures were incorrect. Updated structure and NMR spectral data will be presented.

Nitrocyclopropanation of amino-acid derived enones has led to a series of cyclopropyl peptidomimetics suitable for further elaboration to compounds with the potential for biological activity.

Oxidative cleavage of a series of glycols using NaIO4 on silica gel in the presence of a series of stabilized ylides provides access to a number of synthetically useful alkenes. The ease and general utility of this reaction is demonstrated here using several carbohydrates and amino acid derived glycols.

Synthesis of the 1,1-dicyanomethylene-1-dethiacephalosporin 1a is described. Substitution of the dicyanomethylene moiety for sulfur at position 1 of the cephem nucleus resulted in a highly reactive β-lactam antibacterial.

Formula chem.A very efficient synthesis of (2R,3S) and (25,3R)-4-aminobutane-1,2,3-triol has been developed using either D- or L-glucose as the starting material. A key step is the one-pot conversion of an aldehyde to an amide, the scope of which has been extended to include other carbohydrate-derived aldehydes.

[2251-65-2] C8H4ClF3O (MW 208.56) InChI = 1S/C8H4ClF3O/c9-7(13)5-2-1-3-6(4-5)8(10,11)12/h1-4H InChIKey = RUJYJCANMOTJMO-UHFFFAOYSA-N (forms ester derivatives of alcohols which can be deoxygenated under photolytic conditions using N-methylcarbazole:1-13 reagent for acylation of amines to afford amides14-27) Physical Data: bp 184–186 °C/750 mm Hg; fp 235 °F; d 1.383 g mL−1. Solubility: soluble in CH2Cl2, CHCl3, 1,2-dichoroethane, and THF; reacts with water, alcohols, and other nucleophilic solvents. Form Supplied in: clear liquid. Handing, Storage, and Precautions: corrosive, respiratory irritant, causes burns, moisture sensitive.

Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety. Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action.

The oxidation of α,β-unsaturated ketones with manganese (III) triacetate in benzene furnishes α'-acetoxyenones in good yields.

L'acetylene reagit avec differents chlorures d'acides en presence d'AlCl 3 pour donner des cyclopentenones substituees en 4 et 5. Le chlorure de l'acide methacrylique reagit ainsi avec la butyne-2 pour donner la chloro-5 trimethyl-2,3,5 cyclopentene-2one puis l'addition de AgClO 4 /Et 3 N permet d'obtenir la methylenomycine B

The total synthesis of (+)-mikrolin ( 1a ), a novel fungal metabolite derived from Gilmaniella humicola Barron, has been achieved. The key step entailed a stereoselective hydroxyldirected cis -hydrogenation to set the requisite stereogenic center at C(9).

The total synthesis of dechloromikrolin ( 2Z ), a minor fungal metabolite derived from Gilmaniella humicola Barron, has been achieved. The synthesis resulted in a reassignment of the stereochemistry of the C(2, 3)-disubstituted olefinic bond from E to Z . The biosynthetic implications of this reassignment are discussed.

A benzilic acid rearrangement of a substituted 19-nor-7α,12α-epoxy-12β-hydroxy-9β-podocar-pan-11-one led to a ring contraction in the C ring to furnish the carbocyclic skeleton of the quassinoid, shinjudilactone.

A cyclization of δ-(iodoacetoxy)-α,β-unsaturated ketones using iodotrimethylsilane involved a selective 1,4-addition of the acetate subunit to the enone and furnished δ-lactones in good yield.

L'addition de Diels Alder du butadiene-1,3 avec un naphtalene carbaldehyde conduit au squelette nor-19 podocarpene-12. On prepare une nor-19 podocarpene-13one-12 dont on etudie la structure cristalline. La lactonisation induite par l'iodure de trimethylsilane permet d'obtenir une nor-21 picrasanone-12 dont le noyau ABCD est precurseur des quassinoides

A cyclization of δ-(iodoacetoxy)-α,β-unsaturated ketones using iodotrimethylsilane involved a selective 1,4-addition of the acetate subunit to the enone and furnished δ-lactones in good yield.