Effect of the solvent on the conformation of monocrotaline as determined by isotropic and anisotropic NMR parameters.

The conformation in solution of monocrotaline, a pyrrolizidine alkaloid presenting an eleven-membered macrocyclic diester ring, has been investigated using a combination of isotropic and anisotropic nuclear magnetic resonance parameters measured in four solvents of different polarity (D2 O, DMSO-d6 , CDCl3 , and C6 D6 ). Anisotropic nuclear magnetic resonance parameters were measured in different alignment media, based on their compatibility with the solvent of interest: cromoglycate liquid crystal solution was used for D2 O, whereas a poly (methyl methacrylate) polymer gel was chosen for CDCl3 and C6 D6 , and a poly (hydroxyethyl methacrylate) gel for DMSO-d6 . Whereas the pyrrolizidine ring shows an E6 exo-puckered conformation in all of the solvents, the macrocyclic eleven-membered ring adopts different populations of syn-parallel and anti-parallel relative orientation of the carbonyl groups according to the polarity of the solvent.

Phytochemical Study of Senecio volckmannii Assisted by CASE-3D with Residual Dipolar Couplings and Isotropic 1H/13C NMR Chemical Shifts.

Nine new eremophilanolides, with seven known sesquiterpenoids, and 4-hydroxyacetophenone were isolated from the aerial parts of Senecio volckmannii var. volckmannii. The structures of these compounds were fully characterized using a combination of spectroscopic techniques including multinuclear and multidimensional NMR and mass spectrometry. The recently published Computer Assisted 3D Structure Elucidation (CASE-3D) protocol was applied in the configurational and conformational analysis of many of these eremophilanolides on the basis of Residual Dipolar Couplings (RDCs) and/or DFT predicted 1H/13C chemical shifts.

Computer-Assisted 3D Structure Elucidation (CASE-3D) of Natural Products Combining Isotropic and Anisotropic NMR Parameters.

A computer-assisted structural elucidation (CASE-3D) strategy based on the use of isotropic and/or anisotropic NMR data is proposed to elucidate relative configuration and preferred conformation in complex natural products. The methodology involves the selection of conformational models through the use of the Akaike Information Criterion and scoring of the different configurations. As illustrative examples, the methodology furnished the correct configuration of the already known compounds artemisinin (1) and homodimericin A (2). Revised structures (5 and 6), including their absolute configuration, for the recently reported curcusones I (3) and J (4) are proposed.

Measurement of residual chemical shift anisotropies in compressed polymethylmethacrylate gels. Automatic compensation of gel isotropic shift contribution.

Mechanical compression of polymer gels provides a simple way for the measurement of residual chemical shift anisotropies, which then can be employed, on its own, or in combination with residual dipolar couplings, for structural elucidation purposes. Residual chemical shift anisotropies measured using compression devices needed a posteriori correction to account for the increase of the polymer to solvent ratio inside the swollen gel. This correction has been cast before in terms of a single-free parameter which, as shown here, can be simultaneously optimized along with the components of the alignment tensor while still retaining discriminating power of the different relative configurations as illustrated in the stereochemical analysis of α-santonin and 10-epi-8-deoxycumambrin B.

Highly resolved HSQC experiments for the fast and accurate measurement of homonuclear and heteronuclear coupling constants.

A number of J-upscaled NMR experiments are currently available to measure coupling constants along the indirect F1 dimension of a 2D spectrum. A major drawback is the limited F1 digital resolution that requires long acquisition times in order to achieve reasonably accurate measures. Here is shown how high levels of F1 digital resolution in a multiple-purpose HSQC experiment can be easily achieved by implementing a general J/δ-scaling strategy. In particular, a set of new J-resolved HSQC experiments is presented for a faster and much more accurate J determination in small molecules. Several options and practical aspects are discussed and exemplified by measuring the magnitude and/or the sign of several homo- and heteronuclear coupling constants in one shot.

Self-Sensitized Photooxygenation of 2H-Pyrans: Characterization of Unexpected Products Assisted by Computed Structural Elucidation and Residual Dipolar Couplings.

The UVA (350 nm) irradiation of an α-pyran in the presence of oxygen led to the unexpected formation of a tetraoxygenated compound whose structure could not be unambiguously determined on the basis of conventional (1)H-(13)C correlated experiments. 1,1-ADEQUATE (adequate double quantum transfer experiment) and 1,n-ADEQUATE combined with computer-assisted structure elucidation software led to two structural possibilities involving the formation of either an epoxide or an oxetane. Residual dipolar couplings allowed not only the identification of the compound as a spiroepoxide but also the determination of its relative configuration. To account for its formation, we propose a bisepoxide intermediate that, as opposed to most α,ß-epoxyketones under irradiation, undergoes O-Cß cleavage probably due to the presence of an extra oxygen substituent in the ß position. 1,2-Acyl migration would then proceed stereoselectively to the final product obtained as a single diastereomer.

Unprecedented stereoselective synthesis of cyclopenta[b]benzofuran derivatives and their characterisation assisted by aligned media NMR and 13C chemical shift ab initio predictions.

A new approach to the synthesis of cyclopenta[b]benzofuran derivatives via reaction of 1,3-dicarbonyl compounds with α,ß,γ,δ-unsaturated aldehydes is described. The constitution and configuration of the new products have been firmly established by means of residual dipolar couplings (RDCs) and ab initio (13)C NMR chemical shift predictions.

Synthesis and characterization of an amphiphilic cyclodextrin, a micelle with two recognition sites.

A cyclodextrin derivative (Mod-CD) was synthesized through the monoesterification of beta-cyclodextrin (beta-CD) with 3-((E)-dec-2-enyl)-dihydrofuran-2,5-dione. The compound is an interesting surfactant that can form large aggregates not only through the interaction of the hydrophobic tails as in common amphiphilic compounds but also through the inclusion of the alkenyl chain into the cavity of another Mod-CD molecule. The self-inclusion of the chain in the cavity of cyclodextrin as well as the intermolecular inclusion was demonstrated by 1H NMR measurements that were able to detect methyl groups in three different environments. Besides, in the aggregates of Mod-CD, the cavity is available to interact with external guests such as phenolphthalein, 1-amino adamantane, and Prodan. Phenolphthalein has the same binding constant with Mod-CD and beta-CD, but the equilibrium constant for the interaction with Prodan is about 2 times larger for Mod-CD than for beta-CD. The latter result is attributed to the fact that this probe interacts with the micelle in two binding sites: the cavity of the cyclodextrin and the apolar heart of the micelle as evidenced by the spectrofluorimetric behavior of Prodan in solutions containing different concentrations of Mod-CD.

Withanolides with phytotoxic activity from Jaborosa caulescens var. caulescens and J. caulescens var. bipinnatifida 1.

Seven new withanolides (1-7) were isolated from the aerial parts of Jaborosa caulescens var. caulescens and Jaborosa caulescens var. bipinnatifida. Three of the new compounds are related to jaborosalactones R, S, and T with a delta-lactone side chain and a hemiketal (or ketal) ring formed between a 21-hydroxyl and a 12-ketone (1-3). Compounds 4-7 are trechonolide-type withanolides with a gamma-lactone side chain and a hemiketal (or ketal) ring formed between a 22-hydroxyl and a 12-ketone. Compounds 4 and 5 also contain a hydroxyl group at C-21. Compounds 1, 2, and 7 showed selective phytotoxicity toward monocotyledonous and dicotyledonous species.

Prenylflavonoids from Flourensia fiebrigii.

Three compounds: (2S)-8-(3''-methylbut-2''-enyl)-7,3',4'-trihydroxyflavanone, (2S)-8-(3''-methyl-4''-hydroxy-but-2''-enyl)-7,3',4'-trihydroxyflavanone and (2S)-8-(3''-methyl-4''-hydroxy-but-2''-enyl)-5,3',4'-trihydroxy-7-methoxyflavanone, along with five previously known compounds, were isolated from the aerial parts of Flourensia fiebrigii. Their structures were elucidated by application of various spectroscopic methods, including 1D and 2D NMR techniques.

Modified secoiridoid from Acicarpha tribuloides and inhibition of nitric oxide production in LPS-activated macrophages.

Bioassay-guided fractionation of Acicarpha tribuloides Juss. resulted in the isolation of an uncommon non-glycosylated secoiridoid, tribulolide (1), two known secoiridoid glycosides named secologanic acid (2) and vogeloside (3) as well as two natural chromones, 6,7-dimethoxychromone (4) and 7-hydroxy-6-methoxy-chromone (5). Compounds 1-3 showed inhibition of nitric oxide production in lipopolysaccharide-activated macrophages; their activity is comparable to that of aminoguanidine, a classic inhibitor.

Phytotoxic withanolides from Jaborosa rotacea.

Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.

Antioxidant and free radical scavenging activities of Misodendrum punctulatum, myzodendrone and structurally related phenols.

The peroxyl radical scavenging activity of a dry methanol extract of Misodendrum punctulatum was determined by means of luminol-enhanced chemiluminescence assay, allowing to calculate the total reactive antioxidant potential (TRAP) index equal to 239 +/- 26 microm, expressed in Trolox equivalents. The flavan-3-ol catechin (1) and the phenylbutanone derivative myzodendrone (2) were identified through assay-guided fractionation as active metabolites present in the extract, and their structures were elucidated by chemical and spectroscopic analysis. Three other structurally related synthetic phenols, dehydrozingerone (3), zingerone (4) and myzodendrone aglycone (5), were also analysed using this method. Compounds 1 and 2 were highly effective as free radical scavengers (TRAP = 1257 microm and 1018 microm, respectively) when compared with Trolox (TRAP = 144 microm), used as a standard. Compounds 3 and 5 were also active showing TRAP values of 229 microm and 219 microm, respectively, similarly to that observed for the dry extract. On the other hand, 4 was inactive. Catechin (1) also reduced the production of thiobarbituric acid reactive substances (TBARS) in rat liver homogenates, with IC50 = 26 microg/mL, superior to that obtained for Trolox, IC50 = 73 microg/mL. Compounds 2 and 5 showed IC50 values > 1000 microg/mL, while no activity could be observed for 3, 4, or the extract.

Constituents of two Flourensia species.

The MeOH extract of aerial parts of Flourensia riparia Grisebach (Asteraceae) afforded a sesquiterpene lactone, 4beta-hydroxy-4,10alpha-dimethyl-7alphaH,8alphaH-eudesman-11-ene-8,12-olide, together with septuplinolide, its isomer at positions C-5 and C-10. In addition, known flavonoids, p-hydroxyacetophenone derivatives, carabrone and isoalantolactone were identified. Three known flavonoids and a benzofuran were isolated from Flourensia campestris Wedd.

Azorellane diterpenes from Azorella cryptantha.

Azorella cryptantha yielded the diterpenes, azorellolide and the dihydroderivative, dihydroazorellolide, together with the known yaretol and 1alpha,10beta,4beta,5alpha-diepoxy-7alpha-germacran-6beta-ol. Both possess a carbon skeleton type that may originate from rearrangement of the mulinane skeleton.

15,21-Cyclowithanolides from Jaborosa bergii.

Six new withanolides (1-6) were isolated from the aerial parts of Jaborosa bergii plants and characterized by spectroscopic methods (1D and 2D NMR, MS). Five of the new compounds presented a novel norbornane-type structure in ring D of the steroid nucleus (1-5), resulting from a carbon-carbon bond between C-15 and C-21. The sixth withanolide isolated was the 5alpha-chloro-6beta-hydroxy analogue (6) of 2,3-dehydrojaborosalactol M (7), previously isolated from this plant. Compound 1 showed selective phytotoxicity toward monocotiledoneous and dicotiledoneous species.

Ent-pimarane type diterpenes from Gnaphalium gaudichaudianum.

Fractionation of the methanol extract of Gnaphalium gaudichaudianum DC afforded one new and six known ent-pimarane diterpenes together with velutin, squalene and stigmasterol. The structure of the new compound was established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. Two of the isolated compounds exhibited moderate toxicity in the Artemia salina toxicity test.