A-glucosidase inhibitory activity of kaempferol-3-O-rutinoside

Quercetin, kaempferol and to a lesser extent rutin have been reported to have antidiabetic activities when assessed by various assay models including in vitro alpha-glucosidase inhibition studies. A related structural analogue, kaempferol-3-O-rutinoside (KR) however has not yet been studied for such biological effects. It was found that KR is a potent inhibitor of alpha-glucosidase in vitro with over 8-times more activity than the reference antidiabetic drug, acarbose. Furthermore, KR displayed a synergistic effect with a less potent flavonoid aglycones, kaempferol and quercetin. The structure-activity profile of these drugs and implications of drug combinations are discussed.     

Convallasaponin A, a new 5beta-spirostanol triglycoside from the rhizomes of Convallaria majalis

The rhizomes of Convallaria majalis have been analyzed for their steroidal glycoside constituents, resulting in the isolation of a new 5beta-spirostanol triglycoside, named convallasaponin A, along with two known cardenolide glycosides and a known cholestane glycoside. The structure of convallasaponin A was determined on the basis of extensive spectroscopic analysis, including 2D NMR data, and the results of hydrolytic cleavage. The cardenolide glycosides showed tumor specific cytotoxic activity.     

Penimethavone A,a flavone from a gorgonian-derived fungus Penicillium chrysogenum

A novel flavone, penimethavone A (1), possessing a rare unique methyl group at ring-B, was isolated from the fungus Penicillium chrysogenum cultured from a gorgonian Carijoa sp. collected from the South China Sea. The structure was elucidated by extensive spectroscopic analysis and by comparison with related known compound. Compound 1 showed selective and moderate cytotoxicity against cervical cancer (HeLa) and rhabdomyosarcoma cell lines with IC₅₀ values of 8.41 and 8.18 μM, respectively.     

Spectroscopic Properties of Quercetin Derivatives, Quercetin-3-O-rhamnoside and Quercetin-3-O-rutinoside, in Hydro-organic Mixed Solvents

The characteristic fluorescence properties of quercetin-3- O -rhamnoside (QCRM) and quercetin-3- O -rutinoside (QCRT) were studied in CH₃OH–H₂O and CH₃CN–H₂O mixed solvents. Although QCRM and QCRT are known as nonfluorescent molecules, significant fluorescence emissions were discovered at 360 nm in CH₃OH and CH₃CN when they were promoted to the second excited state. The emission band is broad and structureless and the intensity decreases quickly as the H₂O composition in the solvent increases. When the amount of H₂O exceeds 60% in both mixed solvents, this emission disappears due to the formation of the distorted excited state. This state will be formed due to the strong intermolecular hydrogen bonding between the polar groups of solute and H₂O. As the composition of CH₃OH or CH₃CN in solvent becomes large, the number of molecules having several intramolecular hydrogen bonding increases. Some of these molecules will be changed to a fluorescent species during the decay process, after excitation. The theoretical calculation further supports these results. The change of the lifetimes, quantum yields, and radiative and nonradiative rate constants of molecules was also examined as a function of solvatochromic parameters for CH₃OH–H₂O and CH₃CN–H₂O.     

Electrospray ionization tandem mass spectrometry fragmentation of protonated flavone and flavonol aglycones: a re‐examination

Flavonoids are important phytochemicals which have been intensively studied in the last decades in view of their antioxidant activity, which is of particular importance in the case of flavones and flavonols, that differ in a single 3‐OH group. Mass spectrometry has been used to elucidate the structures of many types of flavonoids and their metabolites. The work we present here is focused on the electrospray ionization tandem mass spectrometry (ESI‐MS/MS) analysis of flavone and flavonols aglycones. Their fragmentation mechanisms in the positive ion mode are described and compared with previously reported mechanisms. We analyzed flavonoid derivatives produced by reaction of the flavonoids with chemically synthesized hypohalous acids (HOCl, HOBr and HOI) and peroxynitrite, reactive species involved in the inflammatory response. All the proposed pathways have been analyzed using computational chemistry methods in order to seek for possible variations and establish the most plausible ones. We observed that the losses of one and two CO molecules can be useful in terms of antioxidant activity prediction. Losses of one and two C₂H₂O groups are also informative in terms of structure and activity predictions. The retro‐Diels‐Alder fragmentations, and subsequent neutral losses, were reviewed and, according to our calculations, the most plausible structures for the product ions were established. These fingerprints will be of great value for differentiating flavonoids from other compounds in complex biological mixtures and for a thorough structural identification of flavonoid aglycones and their in vivo metabolites. Copyright © 2008 John Wiley & Sons, Ltd.     

Structure and fragmentation mechanism of [C3H7S]+ ions

From a comparison of the metastable ion bundance ratios for loss of C₂H₄ and H₂S from [C₃H₇S]⁺ ions in a series of alkyl thio ethers and thiols it was concluded that in most compunds these ion s isomerize to a common structure prior to decomposition in the first field free region. The mechanism for C₂H₄ loss from the [C₃H₇S]⁺ ion gen erated from CH₃SCH₂CH₃ was investigated in detail using ¹³C and ²H labelling. A rearrangement with formation of a cyclic intermediate prior to the decompistion reaction is proposed. The fragmentation is preceded by extensive hydrogen scrabling. The carbon atoms of the expelled C₂H₄ molecule are those of the CH₂?CH₃ moiety.     

Application of positive and negative electrospray ionization, collision-induced dissociation and tandem mass spectrometry to a study of the fragmentation of 6-hydroxyluteolin 7-O-glucoside and 7-O-glucosyl-(1 --> 3)-glucoside

Mass spectrometric methodology based on the combined use of positive and negative electrospray ionization, collision-induced dissociation (CID) and tandem mass spectrometry (MS/MS) has been applied to the structural characterization of 6-hydroxyluteolin 7-O-glucoside and 7-O-glucosyl-(1 --> 3)-glucoside. In-source fragmentation of both glycosides at an increased potential yielded the protonated and deprotonated aglycone, allowing CID spectra to be obtained. The differentiation between quercetin and 6-hydroxyluteolin aglycones was achieved by product ion analysis of the protonated and deprotonated aglycone (m/z 303 and 301), that showed the characteristic product ions (1,3)A at m/z 151 and 153 for quercetin, and m/z 167 and 169 for 6-hydroxyluteolin, consistent with the trihydroxylated A-ring skeleton. In the negative ion mode both glycosides were shown to undergo collision-induced homolytic and heterolytic cleavages of the O-glycosidic bond producing the aglycone radical-anion [Y0-H]-* and Y0(-) product ions. At lower collision energy, various fragmentations involving the glucose moieties were observed with a relatively higher abundance for the monoglucoside compared to the diglucoside. In the latter case both the inner and the terminal glucose residues were involved in the fragmentations, giving useful information on the 1 --> 3 interglycosidic linkage. CID MS/MS analysis of the sodiated molecules gave complementary information for the structural characterization of the studied compounds. Fragmentation mechanisms are proposed for the observed product ions.     

Thermal rearrangement and fragmentation of 1a, 7b-dihydro-1H-cyclopropa[c]cinnolines

Heating of 1a, b in boiling xylene resulted in the rearranged products 2a, b , probably through concerted ring cleavage and 1,5-hydrogen shift. Under the same conditions, 1c reacted slowly to give a mixture from which the fragmentation products 4 and 5 were obtained.     

A new chalcone and a flavone from Andrographis neesiana

Two new flavonoids, 2',4',6',2,3,4-hexamethoxychalcone (1) and 5-hydroxy-7,2',5'-trimethoxyflavone (2) together with a known flavone glycoside, echioidinin 5-O-beta-D-glucopyranoside (3) were isolated from the whole plant of Andrographis neesiana, and the structures were elucidated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and one- and two-dimensional (1D- and 2D)-NMR spectral studies including 1H-1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser enhancement spectroscopy (NOESY) experiments.     

An energy-resolved study of the fragmentation of ionized 1-Penten-3-ol

A detailed energy-resolved study of the fragmentation of CH₂?CHCH(OH)CD₂CD₃ (1-d₅) has been carried out using metastable ion studies and charge exchange techniques, combined with collision-induced dissociation studies to establish the structures of fragment ions. At low internal energies (metastable ions) the molecular ion of 1-d₅ rearranges to the 3-pentanone structure and fragments by loss of C₂H₅ or C₂D₅ leading to the acyl structure, [CH₃CH₂C?O]⁺ or [CD₃CD₂C?O]⁺, for the fragment ion. However, with increasing internal energy of the molecular ion this rearrangement process decreases rapidly in importance and loss of C₂D₅ by direct cleavage, leading to [CH₂?CHCH?OH]⁺, becomes the dominant fragmentation reaction. As a result the [C₃H₅O]⁺ ion seen in the electron impact mass spectrum of 1-penten-3-ol has predominantly the protonated acrolein structure.     

A study of the electron impact-induced fragmentation of 1,6-diaminohexane

The mass spectrometric behaviour of 1,6-diaminohexane has been studied with the help of deuterium labelling in every position of the molecule. Extensive intramolecular exchange reactions between the hydrogen atoms of the amino groups and those of the hydrocarbon chain are responsible for the apparent complexity of the fragmentation mode.     

The mass spectral fragmentation of 1a,3-disubstituted 4-benzoyl-1a,2,3,4- tetrahydrooxazirino

The mass spectrometric behaviour of four 1a,3-disubstituted 4-benzoyl-1a,2,3,4-tetrahydrooxazirino[2,3-a][1,5]benzodiazepines has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a neutral oxygen atom, or oxygen atom plus benzoyl or aryl radicals, or oxygen atom plus CO molecule to yield 2,3-dihydro-1H-1,5-benzodiazepine derivative ions, or 1-benzoyl-2,3-dihydro-1H-1,5-benzodiazepine ions, which could further lose benzoyl to give 2,3-dihydro-1H-1,5-benzodiazepine ions. All compounds also show a tendency to eliminate a benzoyl radical to produce 1a,2,3,4-tetrahydrooxazirino[2,3-a][1,5]benzodiazepine ions. Both oxazirino[2,3-a][1,5]benzodiazepine ions and 2,3-dihydro-1H-1,5-benzodiazepine ions can undergo diazepine ring contraction rearrangement to yield benzimidazole ions by loss of propene or styrenes and other small fragments. The oxazirino[2,3-a][1,5]benzodiazepine ions [M(+)-PhCO] also undergo rearrangement reactions to form benzoxazole ions and benzimidazole ions. Copyright 1999 John Wiley & Sons, Ltd.     

Drypetdimer A: a new flavone dimer from Drypetes gerrardii

A new flavone dimer, drypetdimer A (1), was isolated from Drypetes gerrardii J.Hutch The structure of the new compound was elucidated by detailed spectroscopic analysis such as 1H, 13C NMR, COSY, HMQC, HMBC and HREIMS.     

A study of kynurenine fragmentation using electrospray tandem mass spectrometry

A combination of accurate mass measurement and tandem mass spectrometry (both product ion and precursor ion scans) have been used to characterize the major fragment ions observed in the ESI mass spectrum of kynurenine. Kynurenine is a metabolite of tryptophan found in the human lens and is thought to play a role in protecting the retina from UV-induced damage. Three major fragmentation pathways were evident, following initial elimination either of ammonia, H2O and CO or the imine form of glycine. The latter is proposed to occur via the formation of an ion-molecule complex. In the case of loss of H2O and CO from deaminated kynurenine, there is evidence for an acylium ion intermediate, which is not observed for the loss of H2O and CO directly from protonated kynurenine. Product ion scans of deuterated kynurenine enabled the elucidation of structural rearrangements that were not evident in the spectra of the native compound. Since UV filter compounds can often only be isolated in small quantities from the lens, this study forms the basis for the characterization of novel UV filter compounds using mass spectrometry. The approach presented here may also be useful for the characterization of related classes of small molecules.     

The fragmentation pathways of protonated glycine: A computational study

Numerous studies have demonstrated that protonated aliphatic amino acids, [H2NCHRCO2H + H]+, fragment in the gas phase to form iminium ions, H2N=CHR+. Unfortunately none of these studies have probed the structure of the neutral(s) lost as well as the mechanism of fragmentation. Three main mechanisms have been previously proposed: (1) loss of the combined elements of H2O and CO; (2) loss of dihydroxycarbene (HO)2C: and (3) loss of formic acid, HC(=O)OH. Herein, ab initio and density functional theory calculations have been used to calculate the key reactants, transition states, and products of these and several other competing reaction channels in the fragmentation of protonated glycine. The loss of the combined elements of H2O and CO is thermodynamically and kinetically favored over the alternative formic acid or (HO)2C fragmentation processes.     

A study of η-allyl(η-cyclopentadienyl)- dicarbonylmanganese salts

New substituted η³-allyl(η⁵-cyclopentadienyl)dicarbonylmanganese cations have been prepared as their tetrafluoroborates. They readily add a wide range of nucleophiles yielding η²-alkene(η⁵-cyclopentadienyl)dicarbonylmanganese complexes. Of the latter, in general only those involving terminal alkenes are sufficiently stable to permit ready isolation; otherwise metal-free alkenes are obtained. Regioselectivity in these additions depends on the nucleophile.