Uncatalyzed reaction of silyl ketene acetals with oxalyl chloride: a straightforward preparation of symmetrical pulvinic acids

[reaction: see text] Several natural pulvinic acids were synthesized. Silyl ketene acetals derived from methyl arylacetates (4 equiv) reacted with oxalyl chloride at -78 degrees C, without the need of adding a catalyst. After treatment of the crude diketones with DBU and acidification with hydrochloric acid, symmetrical pulvinic acids methyl esters were obtained. Saponification of the methyl esters afforded the corresponding pulvinic acids in 60-70% overall yields from oxalyl chloride.     

Bioinspired Synthesis of Pulvinic Acids Including Xerocomic Acid and Fluorescence Properties of Bis-lactone Intermediates

A set of representative pulvinic acids were synthesised using a bioinspired strategy. Terphenyl-quinones (polyporic acid scaffold) were prepared via sequential Suzuki-Miyaura couplings allowing access to unsymmetrically substituted derivatives in a one-pot protocol. Subjected to the action of acetic anhydride and DMSO, quinones were converted into bis-lactone intermediates. Methanolysis and deprotection achieved the total syntheses of the corresponding pulvinic acids. Following this general strategy, symmetrical pulvinic, atromentic, variegatic acids and unsymmetrical congener pinastric, iso-pinastric, xerocomic and iso-xerocomic acids were prepared in fair yields. Fluorescence properties were observed for the bis-lactone intermediates and, as a complement to this synthetic work, optical properties were measured, and fluorescence quantum yields were determined for the bis-lactone pigments.     

Separation and identification of lichen acids of the pulvinic acid series

Lichen acids, pulvinic acid, vulpinic acid, pinastric acid, leprapinic acid, lsoplnastric acid and pulvinic acid dilactone, which occur in certain yellow varieties of lichens and are difficult to separate, have been successfully separated and identified by TLC on chlorobenzene-impregnated silica gel plates.     

Development of models for prediction of the antioxidant activity of derivatives of natural compounds

Antioxidants are important for maintaining the appropriate balance between oxidizing and reducing species in the body and thus preventing oxidative stress. Many natural compounds are being screened for their possible antioxidant activity. It was found that a mushroom pigment Norbadione A, which is a pulvinic acid derivative, shows an antioxidant activity; the same was found for other pulvinic acid derivatives and structurally related coumarines. Based on the results of in vitro studies performed on these compounds as a part of this study quantitative structure–activity relationship (QSAR) predictive models were constructed using multiple linear regression, counter-propagation artificial neural networks and support vector regression (SVR). The models have been developed in accordance with current QSAR guidelines, including the assessment of the models applicability domains. A new approach for the graphical evaluation of the applicability domain for SVR models is suggested. The developed models show sufficient predictive abilities for the screening of virtual libraries for new potential antioxidants.     

Pinastric acid revisited: a complete NMR and X-ray structure assignment

Chemical investigation of a terrestrial lichen has yielded the pulvinic acid derivative pinastric acid (4). The structure of 4 was secured by detailed spectroscopic analysis as well as via a single X-ray diffraction study. This is the first report of the X-ray structure and 2D NMR assignment of pinastric acid (4). Pinastric acid (4) displayed antitumour, antiviral and antimicrobial (both antibacterial and antifungal) activities. Whilst the antiviral and antimicrobial activities are consistent with previous findings of 4 this is the first report of the antitumour properties for the compound.     

Synthesis of vulpinic and pulvinic acids from tetronic acid

A common precursor, tetronic acid, was used in the synthesis of several vulpinic acids and pulvinic acids, which are pigments found in several lichens and mushrooms. The key features of this method are a two-step alkylidenation of benzyl tetronate and a Suzuki-Miyaura cross-coupling. The synthesis of several natural products, vulpinic acid, pinastric acid, xerocomic acid is described.     

One Pot One Step Photoconversion of Pulvinic Acid Dilactone to p-Methoxyvulpinic Acid

The utility of singlet oxygen-methanol as a reagent for nuclear methoxylation of complex organic natural products is illustrated by a one pot one step photoconversion of pulvinic acid dilactone to p-methoxyvulpinic acid. The study is important from biogenetic considerations.     

Nature of light-absorbing pigments from Brazilian lichens identified by Raman spectroscopy

Light-absorbing pigments from different chemical classes have been identified from the lichens Usnea sp. and Crocodia aurata using Raman spectroscopy supported by quantum mechanical DFT calculations. Raman spectra were obtained directly from the lichen tissues as well as from isolated extracts. Usnic acid, a chemomarker of Usnea spp has been reported together with a minor constituent, namely stictic acid, which has been unambiguously identified by ¹H and ¹³C NMR spectral analysis. The structures of calycin and pulvinic dilactone isolated from Crocodia aurata have been confirmed by single crystal X-ray diffraction. The ubiquitous carotenoids have been characterized by FT-Raman and dispersive Raman microimaging in tissues of Usnea sp. and C. aurata, respectively. The Raman map has revealed the presence of a mixture of carotenoids heterogeneously distributed in the upper layer of C. aurata. In this work we have demonstrated that Raman spectroscopy can be used to monitor aromatic and conjugated polyenic pigments in different layers of lichen tissues.     

Simple method for reversed-phase high-performance liquid chromatographic analysis of fungal pigments in fruit-bodies of Boletales (Fungi)

A reversed-phase HPLC method has been developed for the analysis of hydroxylated pulvinic acid derivatives which are responsible for the pigmentation of fruit-bodies belonging to the order Boletales (Fungi). Variegatic, xerocomic and atromentic acid as well as variegatorubin were detected and separated in methanolic extracts of Boletus permagnificus and Xerocomus parasiticus, and the pigment profile of these species was compared. The identity of the pigments was confirmed by means of LC-atmospheric pressure chemical ionization (APCI) mass spectrometry.     

Conformational and Cs+ complexation properties of norbadione-A: a molecular modeling study

We report a quantum mechanical (QM) and classical molecular dynamics (MD) study of the conformational and complexation properties of norbadione-A (NBA), a key pigment involved in the Cs+ complexation by mushrooms. The Z versus E isomers of its pulvinic moieties are compared in their neutral (Pulv0), mono- (Pulv(-1)) and di-deprotonated (Pulv(-2)) states, and the 1H chemical shifts are calculated ab initio. Pulv(-1) is found to be stabilized in the E form by an internal COOH(-)O(enolate) hydrogen-bond. No energy minimum is found for the corresponding COO(-)HO(enol) state, indicating that the conjugated enol function of Pulv0 is more acidic than the COOH function. Further deprotonation leads to the Z and E forms of Pulv(-2) that are close in energy and both account for a marked downfield shift delta of ortho-H8 protons. A similar shift is found upon deprotonation of the enol function of an ester analogue of Pulv0. Therefore, contrary to previous assumptions (ref. 7: P. Kuad, et al., J. Am. Chem. Soc., 2005, 127, 1323), the large shift of delta(H8) around pH 9.5 upon deprotonation of NBA or of pulvinic acid cannot be taken as an indicator of an E-to-Z conformational switch, but merely reflects the pH-induced conformational change of the carboxylate group adjacent to the (H8)-ring. The QM and MD studies on NBA(2-) and NBA(4-) support the view that both species prefer the E/E form with two intramolecular COOH(-)O(enolate) hydrogen-bonds in the gas phase and in solution. Finally, we simulated mono- and di-nuclear complexes of Cs+ with NBA(2-) and NBA(4-) by MD, showing that only the NBA(4-) state populated at high pH values can bind two Cs+ cations, with both E and Z conformations of the pulvinic arms.     

Asymmetric total synthesis of botcinic acid and its derivatives: synthetic revision of the structure of botcinolides

The stereoselective total syntheses of botcinic acid, botcinic acid methyl ester, 3-O-acetylbotcinic acid methyl ester, botcineric acid, and botcinin E were achieved. The structures of these compounds have been unequivocally determined through their total synthesis, and they are identified with the revised structures of botcinolide, 4-O-methylbotcinolide, 3-O-acetyl-5-O-methylbotcinolide, homobotcinolide, and 2-epibotcinolide, respectively.     

Total synthesis of macrocyclic glycosides, clemochinenosides A and B, and berchemolide, by fluorous mixture synthesis

The total synthesis of clemochinenoside A and the first total syntheses of clemochinenoside B and berchemolide were achieved simultaneously via macrocyclization of 4-O-(4-O-^F13benzyl-β-d-glucopyranosyl)syringic acid with 4-O-(4-O-^F17benzyl-β-d-glucopyranosyl)vanillic acid by a fluorous mixture synthetic method. The spectroscopic data of the synthetic products were identical with those of the natural products, although the optical rotation of clemochinenoside A differed from the published values in sign and magnitude.     

Raman spectroscopy of hot desert, high altitude epilithic lichens

Twenty-three highly-coloured lichen specimens belonging to the genera Candelariella, Aspicilia and Xanthoria from high altitude sites in the Atacama Desert, Chile, 2300-4500 metres, have been analysed non-destructively by Raman spectroscopy. The vibrational band assignments in the spectra of the specimens, which were still attached to their limestone or sandstone substrata, were accomplished by comparison with the chemical compositions obtained from wet chemical extraction methods. Carotenoids and chlorophyll were found in all specimens as major components and the characteristic spectral signatures of calcium oxalate monohydrate (whewellite) and dihydrate (weddellite) could be identified; chemical signatures were found for these materials even in lichen thalli growing on the non-calcareous substrata, indicating probably that the calcium was provided here from wind- or rain-borne sources. The Raman spectral biomarkers for a variety of protective biomolecules and accessory pigments such as usnic acid, calycin, pulvinic acid dilactone and rhizocarpic acid have been identified in the lichens, in broad agreement with the chemical extraction profiles. The present study indicates that some form of non-destructive taxonomic identification based on Raman spectroscopy was also possible.     

<em>In Vitro</em> Anti-diabetic Activities and Chemical Analysis of Polypeptide-k and Oil Isolated from Seeds of <em>Momordica charantia</em> (Bitter Gourd)

The amino acid and fatty acid composition of polypeptide k and oil isolated from the seeds of Momordica charantia was analysed. The analysis revealed polypeptide k contained 9 out of 11 essential amino acids, among a total of 18 types of amino acids. Glutamic acid, aspartic acid, arginine and glycine were the most abundant (17.08%, 9.71%, 9.50% and 8.90% of total amino acids, respectively). Fatty acid analysis showed unusually high amounts of C18-0 (stearic acid, 62.31% of total fatty acid). C18-1 (oleic acid) and C18-2 (linoleic acid) were the other major fatty acid detected (12.53% and 10.40%, respectively). The oil was devoid of the short fatty acids (C4-0 to C8-0). Polypeptide k and oil were also subjected to in vitro α-glucosidase and α-amylase inhibition assays. Both polypeptide k and seed oil showed potent inhibition of α-glucosidase enzyme (79.18% and 53.55% inhibition, respectively). α-Amylase was inhibited by 35.58% and 38.02%, respectively. Collectively, the in vitro assay strongly suggests that both polypeptide k and seed oil from Momordica charantia are potent potential hypoglycemic agents.     

Photodissociation/gas-diffusion separation and fluorimetric detection for the analysis of total and labile cyanide in a flow system

Total cyanide species are determined in a flow injection system which includes UV-photodissociation, gas-diffusion separation and spectrofluorimetric detection. Without the irradiation step, only cyanide easily released in acid medium, i.e. labile cyanide, is determined. Cyanide diffuses through a microporous PTFE membrane from an acid donor stream to a sodium hydroxide acceptor stream. Then, the transferred cyanide reacts with ¶o-phthalaldehyde and glycine to form a highly fluorescent isoindole derivative. Complete cyanide recoveries were obtained for the most important metal cyanide complexes found in environmental samples, excepting cobaltocyanide. The sampling frequency for total cyanide was 4 samples h^–1 and the detection limit was 0.4 μg L^–1. Recoveries of total cyanide from river water obtained with this method are about 90% of those obtained with APHA Method 4500-CN C for total cyanide.     

Facile method for the synthesis of oseltamivir phosphate

A ten-step scheme for the preparation of an antiviral agent, ethyl (3R,4R,5S)-4-acetylamino-5-amino-3-(pent-3-yloxy)cyclohex-1-enecarboxylate phosphate, from (-)-shikimic acid was studied. The main parameters of the synthesis were determined and the optimal conditions for the preparation of the intermediate compounds were selected. The total yield of oseltamivir phosphate calculated based on (-)-shikimic acid was 27%.     

Total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives

We report the first total synthesis of 3,5-O-dicaffeoylquinic acid and its derivatives, 3,5-O-diferuloylquinic acid and 3,5-(3,4-dimethoxycinnamyl)quinic acid, in a nine-step sequence. The key step involves Knoevenagel condensations between vanillin, 3,4-dimethoxybenzaldehyde or 4-hydroxy-3-methoxybenzaldehyde and the dimalonate ester of quinic acid.     

Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1

The total synthesis of the potent anti-inflammatory lipid mediator Protectin D1 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C10 and C17 were obtained via a chiral pool strategy from (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane and 3,4-O-isopropylidene-2-deoxy-d-ribose, respectively. Wittig reactions, Takai olefination, Pd⁰/Cu^I Sonogashira coupling, and Zn(Cu/Ag) reduction completed the total synthesis of Protectin D1.     

Barium coordination polymers based on fluorinated and fluorine-free benzene-dicarboxylates: Mechanochemical synthesis and spectroscopic characterization

A series of new Ba-based coordination polymers (CPs) were mechanochemically synthesized by milling Ba-hydroxide samples with perfluorinated and fluorine-free benzene-dicarboxylic acids, including tetrafluoroisophthalic acid (H₂mBDC-F₄), tetrafluorophthalic acid (H₂oBDC-F₄), isophthalic acid (H₂mBDC) and phthalic acid (H₂oBDC). The new fluorinated CPs: [Ba(mBDC-F₄)·0.5H₂O] (1) and [Ba(oBDC-F₄)·1.5H₂O] (2) are compared to their nonfluorinated counterparts: [Ba(mBDC)·2.5H₂O] (3), and [Ba(oBDC)·1H₂O] (4). These materials are thoroughly characterized using powder X-ray diffraction. The products obtained by milling are all hydrated but vary in their water contents. Compositions and local structures are investigated by elemental analysis, thermal analysis, MAS NMR and attenuated total reflection-infrared spectroscopy. These materials exhibit high thermal stabilities but small surface areas that remain unchanged even after thermal treatments.     

Changes in Organic Acids,Phenolic Compounds,and Antioxidant Activities of Lemon Juice Fermented by Issatchenkia terricola

High content of citric acid in lemon juice leads to poor sensory experience. The study aimed to investigate the dynamics changes in organic acids, phenolic compounds, and antioxidant activities of lemon juice fermented with Issatchenkia terricola WJL-G4. The sensory evaluation of fermented lemon juice was conducted as well. Issatchenkia terricola WJL-G4 exhibited a potent capability of reducing the contents of citric acid (from 51.46 ± 0.11 g/L to 8.09 ± 0.05 g/L within 60 h fermentation) and increasing total phenolic level, flavonoid contents, and antioxidant activities compared to those of unfermented lemon juice. A total of 20 bioactive substances, including 10 phenolic acids and 10 flavonoid compounds, were detected both in fermented and unfermented lemon juice. The lemon juice fermented for 48 h had better sensory characteristics. Our findings demonstrated that lemon juice fermented with Issatchenkia terricola exhibited reduced citric acid contents, increased levels of health-promoting phenolic compounds, and enhanced antioxidant activities.