Manuel Gonzalez Sierra

13C NMR spectral and conformational analysis of 8-O-4' neolignans

Abstract The 13C NMR spectra of the erythro and threo forms of representative members of the 8-O-4′ type of neolignans were recorded and the signals assigned. Based on these assignments and on the comparison with previously reported 1H NMR data, the most probable conformations for the above mentioned stereoisomers are suggested.

Chemically engineered extracts as an alternative source of bioactive natural product-like compounds

The access to libraries of molecules with interesting biomolecular properties is a limiting step in the drug discovery process. By virtue of a long molecular evolution process, natural products are recognized as biologically validated starting points in structural space for library development. We introduce here a strategy to generate natural product-like libraries. A semisynthetic mixture of compounds was produced by diversification of a natural product extract through the chemical transformation of common chemical functionalities in natural products into chemical functionalities rarely found in nature. The resulting mixture showed antifungal activity against Candida albicans, whereas the starting extract did not show such activity. Bioguided fractionation led to the isolation of a previously undescribed active semisynthetic pyrazole. The result illustrates how biological activity can be generated by designed chemical diversification of a natural product mixture, and represents the proof of principle of an alternative strategy for producing natural product-like libraries from natural products libraries.

Isolation of antifungal saponins from Phytolacca tetramera, an Argentinean species in critic risk

The methanolic extract of the berries of Phytolacca tetramera, an Argentinean species submitted to a great anthropic impact, and therefore in critic risk of extinction, not previously studied, showed antifungal activity against opportunistic pathogenic fungi. Through fractionation of the extract followed by agar dilution assays, three monodesmosidic triterpenoid saponins have been isolated from the butanolic extract of P. tetramera. The structures were established as phytolaccosides: B [3-O-beta-D-xylopiranosyl-phytolaccagenin], E [3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-xylopiranosyl-phytolaccagenin]. and F [3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl-phytolaccagenic acid]. The three saponins belong to the olean-type triterpenoid saponins, with 28,30 dicarboxylic groups and an olefinic double bond on C-12. Phytolaccosides B and E but not phytolaccoside F, showed antifungal activities against a panel of human pathogenic opportunistic fungi. Phytolaccoside B was the most active compound and showed the broadest spectrum of action. The most sensitive fungus was Trichophyton mentagrophytes.

Interaction of divalent metal ions withd-gluconic acid in the solid phase and aqueous solution

Abstract The interaction of d -gluconic acid with MnII, CoII, NiII, CuII, CdII, HgII and PbII has been investigated. Compounds of the type Mn( d -gluconate)2·3H2O, Co( d -gluconate)2·3H2O, Ni( d -gluconate)2·3H2O, Cu( d -gluconate)2·3H2O, Cd( d -gluconate)2, Hg( d -gluconate)OH and Pb( d -gluconate)2 have been isolated. These metal-sugar salts were characterized by elemental, thermogravimetric analyses and FT-IR, UV-vis absorption, EPR and13C NMR spectroscopies. In addition, a quantitative study of the equilibria involved in the interaction of this sugar and the above mentioned metal ions in an aqueous medium was carried out by means of potentiometric measurements of the hydrogen ion concentrations at 20°C andμ = 0.100M (NaNO3). On the basis of spectroscopic studies, possible structures of these complex species were discussed.

Antifungal activity of extracts and prenylated coumarins isolated from Baccharis darwinii Hook & Arn. (Asteraceae).

The petroleum ether extract of Baccharis darwinii showed activity against Cryptococcus neoformans and dermatophytes. Bioactivity-guided fractionation of Baccharis darwinii has resulted in the isolation of three coumarins: 5’-hydroxy aurapten (anisocoumarin H, 1), aurapten (7-geranyloxycoumarin, 2) and 5’-oxoaurapten (diversinin, 3). The structures of these compounds were characterized by spectroscopic methods. These compounds were evaluated for their antimicrobial activity against a panel of each, bacteria and fungi. Compound 3 showed the best activities against Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes with MICs = 15.6 µg/mL, followed by compound 1 whose MICs against the same fungi were 62.5 µg/mL. In addition they showed fungicidal rather than fungistatic activity. Both compounds showed moderate activity (MICs = 125 µg/mL) against Cryptococcus neoformans. This is the first report of the presence of compound 1 in B. darwinii.

Interaction of zinc(II) ion withd-aldonic acids in the crystalline solid and aqueous solution

Abstract The interaction of zinc(II) ion with d -glucoheptonic acid, d -gluconic acid, d -gulonic acid, d -galactonic acid and d -ribonic acid has been investigated and compounds of the type Zn( d -glucoheptonate)2·3H2O, Zn( d -gluconate)2·3H2O, Zn( d -gulonate)2·3H2O, Zn( d -galactonate)2·3H2O and Zn( d -ribonate)2·H2O, have been isolated. These metal-sugar salts were characterized by elemental analysis, FT IR spectroscopy, thermogravimetric analysis and13C-NMR. Spectroscopic measurements showed similar patterns between these complexes and the structurally identified Mn( d -gluconate)2·2H2O. The zinc(II) ion is binding to two ligand molecules through the car☐ylate and OH groups of each sugar, as well as to water molecules. The potentiometric measurements in aqueous solutions for the systems formed by the sugar acids investigated and the zinc(II) ion at different metal-ligand ratios showed the 1:1 complexes formation. On the basis of the13C NMR, the participation of C-1 and C-2 in this complex formation was verfiied. Due to the hydroxide precipitation, quantitative evaluation of the stability constants was not performed.

Molluscicidal sesquiterpene lactones from species of the tribe Vernonieae (Compositae).

Schistosomiasis is caused by parasitic flatworms of the genus Schistosoma, and some snails, particularly of the genus Biomphalaria (Planorbidae), are directly implicated in the transmission of the disease. Continuing with our investigations of bioactive plant constituents, we evaluated and report in the present article, the molluscicidal effects of 16 sesquiterpene lactones, as well as the commercial reagents tetrahydrofuran, furfural, and furfuryl alcohol, on an adult population of B. peregrina. The natural sesquiterpene lactones tested are characteristic constituents of species of the tribe Vernonieae, family Asteraceae. Compounds 1-3 and 7 came from a Bolivian collection of Vernonanthura pinguis, compounds 4 and 5 from an Argentine collection of Cyrtocymura cincta var. cincta, 6 was obtained from a Bolivian collection of Eirmocephala megaphylla, 8-14 from an Argentine collection of Centratherum punctatum ssp. punctatum, and compounds 15 and 16 were obtained by chemical derivatization from 5 and 14, respectively. Ten of the sesquiterpene lactones displayed moderate molluscicidal activity (LD50<100 microg/ml). Commercial reagents were inactive.

Eudesmanes from Pluchea sagittalis. Their antifeedant activity on Spodoptera frugiperda

Eudesmane-type sesquiterpenoids 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxy-11-hydroxy-6,7-dehydroeudesman-8-one (1) and 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha,7alpha,11-trihydroxyeudesman-8-one (2), together with 10 known structurally related eudesmanes were isolated from the CHCl3 extract of aerial parts of Pluchea sagittalis (Lamarck) Cabrera. Their structures were deduced by extensive application of 1 and 2D NMR spectroscopic techniques and high and low resolution CIMS. X-ray crystallographic analysis of the known compound 3alpha-(2,3-epoxy-2-methylbutyryloxy)-4alpha-formoxycuauthemone (9) is reported here for the first time, and confirms the structural features for the series of the reported eudesmanes. All eudesmanes were tested for their antifeedant activity by incorporating them to an artificial diet of larvae of the polyphagous insect Spodoptera frugiperda at a concentration of 100ppm. Our results, from feeding choice tests, indicated that most of the compounds deter larval feeding at the cited concentration.

Bismuth(III) complexes of d-gluconic acid. Studies in aqueous solution and in the solid phase

The system formed between bismuth(III) ion and D-gluconic acid was potendometrically studied in aqueous solution. Measurements were carried out at 20.0 and 25.0+/-0.1 degrees C and the ionic strength was maintained at 0.100 M with NaNO3. The potentiometric curves showed the release of four protons in addition to the carboxylic one, leading to the formation of complexes with different degrees of deprotonation. Since the first chelate was completely formed at low pH, competition equilibria involving ethylenediaminetetraacetic acid or nitrilotriacetic acid ligands were used to calculate the corresponding equilibrium constant. Coordination bonding sites for metal-ligand interactions were inferred from C-13 NMR spectroscopy. According to the obtained results, the complex formed at acid pH would present a carboxylate coordination and those formed at high pH would involved a bonding with the oxygens of carbons 2, 3, 4 and 5. On the other hand, the complex Bi(C6H9O7). H2O was isolated and characterized by elemental and thermogravimetric analyses and by Fourier transform infra-red (FT-IR) spectroscopy. While the thermogravimetric analyses confirmed the water content in the solid complex, the IR spectra showed a monodentate carboxylate coordination

Spectroscopic and theoretical study of aromatic α-hydroxy hydrazones and their copper(II) complexes in dioxane-water mixtures

Abstract Two aromatic α-hydroxy hydrazone, N-phenyl-N′ (2-hydroxy-1-phenylmethylene hydrazine) and N-phenyl-N′ (2-hydroxy-1-naphthylmethylene hydrazine), and their copper(II) complexes have been studied in both 30% and 70% dioxane-water (v/v) systems. Structural analysis of the anionic forms of the free compounds has been performed using 13C NMR and electronic absorption spectroscopies and semiempirical MO calculations. The equilibrium constants for the deprotonation reactions of the hydrazones and for their coordination with Cu(II) ion were studied by spectrophotometric titration. Coordination binding sites and stereochemistry of the chelates were inferred from NMR spectroscopy.