Acid Lactone Research Articles

ChemInform Abstract: 3‐Alkyl‐1,2‐cyclopentanediones by Negishi Cross‐Coupling of a 3‐Bromo‐1,2‐cyclopentanedione Silyl Enol Ether with Alkylzinc Reagents: An Approach to 2‐Substituted Carboxylic Acid γ‐Lactones, Homocitric and Lycoperdic Acids.

AbstractProduct (IIIe) can be converted to give homocitric acid lactone.

Improved Second Generation Iron Pincer Complexes for Effective Ester Hydrogenation

AbstractHydrogenation of esters to alcohols with a well‐defined iron iPr2PNP pincer complex has been recently reported by us and other groups. We now introduce a novel and sterically less hindered Et2PNP congener that provides superior catalytic activity in the hydrogenation of various carboxylic acid esters and lactones compared to the known complex. Successful hydrogenation proceeds under relatively mild conditions (60 °C) with lower catalyst loadings.magnified image

Analysis of amino acid substitutions in AraC variants that respond to triacetic acid lactone.

The Escherichia coli regulatory protein AraC regulates expression of ara genes in response to l-arabinose. In efforts to develop genetically encoded molecular reporters, we previously engineered an AraC variant that responds to the compound triacetic acid lactone (TAL). This variant (named "AraC-TAL1") was isolated by screening a library of AraC variants, in which five amino acid positions in the ligand-binding pocket were simultaneously randomized. Screening was carried out through multiple rounds of alternating positive and negative fluorescence-activated cell sorting. Here we show that changing the screening protocol results in the identification of different TAL-responsive variants (nine new variants). Individual substituted residues within these variants were found to primarily act cooperatively toward the gene expression response. Finally, X-ray diffraction was used to solve the crystal structure of the apo AraC-TAL1 ligand-binding domain. The resolved crystal structure confirms that this variant takes on a structure nearly identical to the apo wild-type AraC ligand-binding domain (root-mean-square deviation 0.93 Å), suggesting that AraC-TAL1 behaves similar to wild-type with regard to ligand recognition and gene regulation. Our results provide amino acid sequence-function data sets for training and validating AraC modeling studies, and contribute to our understanding of how to design new biosensors based on AraC.

Direct oxidative lactonization of alkenoic acids mediated solely by NaIO4: beyond a simple oxidant

Triflic acid-catalyzed direct oxidative lactonization of alkenoic acids mediated solely by NaIO4 without halogen salts is described. Sodium periodate works not only as an oxidant, but also as an active reagent and directly mediates the lactonization. A new cheap, green, and practical oxidative lactonization approach has been developed using NaIO4 as the sole reagent.

Gallium-catalyzed reductive lactonization of γ-keto acids with a hydrosilane

Gallium chloride efficiently catalyzes cyclization of γ-keto carboxylic acids in the presence of PhSiH3 to produce the corresponding γ-lactone derivatives.

The Physiological Effects of Dandelion (Taraxacum Officinale) in Type 2 Diabetes.

The tremendous rise in the economic burden of type 2 diabetes (T2D) has prompted a search for alternative and less expensive medicines. Dandelion offers a compelling profile of bioactive components with potential anti-diabetic properties. The Taraxacum genus from the Asteraceae family is found in the temperate zone of the Northern hemisphere. It is available in several areas around the world. In many countries, it is used as food and in some countries as therapeutics for the control and treatment of T2D. The anti-diabetic properties of dandelion are attributed to bioactive chemical components; these include chicoric acid, taraxasterol (TS), chlorogenic acid, and sesquiterpene lactones. Studies have outlined the useful pharmacological profile of dandelion for the treatment of an array of diseases, although little attention has been paid to the effects of its bioactive components on T2D to date. This review recapitulates previous work on dandelion and its potential for the treatment and prevention of T2D, highlighting its anti-diabetic properties, the structures of its chemical components, and their potential mechanisms of action in T2D. Although initial research appears promising, data on the cellular impact of dandelion are limited, necessitating further work on clonal β-cell lines (INS-1E), α-cell lines, and human skeletal cell lines for better identification of the active components that could be of use in the control and treatment of T2D. In fact, extensive in-vitro, in-vivo, and clinical research is required to investigate further the pharmacological, physiological, and biochemical mechanisms underlying the effects of dandelion-derived compounds on T2D.

A New HPLC Method for Analysis of Natural Monacolin K in Red Yeast Rice Pharmaceutical Preparations

Monacolin K (lovastatin or mevinolin) is a naturally occurring hypocholesterolemic statin used to prevent cardiovascular diseases for those persons suffering from hypercholesterolemia, a condition characterized by very high levels of cholesterol in the blood. It is originally derived from the fungus Monascus ruber and Monascus purpureus family Monascaceae. Monacolin K is a lactone polyketide derived compound converted in the body to the active form, B-hydroxy acid of monacolin K. It acts by inhibiting the hepatic HMG-CoA Reductase enzyme. In this paper, we report a selective precise and accurate new HPLC method for analysis of both lactone form and acid form of monacolin k in red rice pharmaceutical preparations.

Hyalodendriellins A–F, new 14-membered resorcylic acid lactones from the endophytic fungus Hyalodendriella sp. Ponipodef12

Six new 14-membered resorcylic acid lactones (RALs), named hyalodendriellins A–F (1–6), were isolated from the culture of the endophytic fungus Hyalodendriella sp.

An efficient synthesis of an exo-enone analogue of LL-Z1640-2 and evaluation of its protein kinase inhibitory activities.

An efficient synthesis of an exo-enone analogue (5) of resorcylic acid lactone (RAL), natural product LL-Z1640-2 (1), has been achieved using a Ni-catalysed regioselective reductive coupling macrocyclisation of an alkyne-aldehyde as a key step. The synthetic route is significantly shorter than those for the natural product and avoids the isomerisation problem of the cis-double bond in the molecule. The preliminary biological evaluation showed that the exo-enone analogue is a potent inhibitor of several important kinases relevant to cancer drug development.

12-Membered Resorcylic Acid Lactones Isolated from Saccharicola bicolor, an Endophytic Fungi from Bergenia purpurascens

Two new resorcylic acid lactones, 13-hydroxyhidroresorcylide (1) and 12-hydroxyhidroresorcylide (2), along with four known congeners (3-6) were isolated from Saccharicola bicolor, an endophytic fungus from Bergenia purpurascens. Their structures were elucidated by interpretation of the spectroscopic evidence.

ChemInform Abstract: A Carbohydrate Approach for the First Total Synthesis of Cochliomycin C (I): Stereoselective Total Synthesis of Paecilomycin E, Paecilomycin F and 6′‐epi‐Cochliomycin C.

AbstractStarting from readily available sugar D‐lyxose, a unique strategy for the total synthesis of natural resorcylic acid lactones involving an Ohira—Bestmann alkynylation, ring closing metathesis, and regioselective methylation under Mitsunobu conditions as key steps is accomplished.

Stereoselective total synthesis of the antiplasmodial resorcylic acid lactone paecilomycin F

A facile and convergent approach for the total synthesis of 14-membered resorcylic acid lactone paecilomycin F is described. The synthesis emanates from the readily available inexpensive (+)diethyl L-tartrate. Mitsunobu etherification, Stille coupling and ring-closing metathesis are key steps in the synthesis.

Modifying the Surface Properties of Heterogeneous Catalysts Using Polymer-Derived Microenvironments

This work uses transition state theory as applied to thermodynamically non-ideal systems to explore the origins of improvements in the stability and activity of supported metal catalysts containing polymer-derived microenvironments. The hydrogenation of triacetic acid lactone (TAL), which is the first step in the production of biorenewable sorbic acid, is used as a probe for the influence of a poly(vinyl alcohol)-derived (PVA-derived) microenvironment on the reduction of moderately polar compounds. The presence of the microenvironment causes a moderate decrease in the rate of TAL hydrogenation without causing a substantial change in the measured activation barrier or reaction orders. This decrease is explained in the context of a local solvation environment generated by the PVA. For comparison, the hydrogenation of lactic acid (LA) is used as a probe for the influence of a PVA-derived microenvironment on the adsorption of polar compounds. In this case, the reaction order in LA increases from zero-order to 0.3-order, indicating that the surface coverage by lactate is decreased by the presence of the microenvironment. The results presented indicate that polymer-derived microenvironments act as pseudo-solvents that alter the surface properties of supported metal catalysts, and we suggest that modifying catalysts with polymer-derived microenvironments is a generalizable methodology with applications in liquid-phase biomass conversion reactions.

Hypothemycin inhibits tumor necrosis factor-α production by tristetraprolin-dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages

Hypothemycin, a resorcylic acid lactone polyketide, has been shown to inhibit oncogenic ras-transformation and T cell activation. In the present study, we investigated the effect of hypothemycin on tumor necrosis factor-α (TNF-α) production in macrophages and the molecular mechanisms involved in this effect. Hypothemycin potently suppressed the TNF-α production without affecting nitric oxide production in lipopolysaccharide (LPS)-stimulated macrophages. However, hypothemycin had no effect on the activity of TNF-α-converting enzyme, a key enzyme for converting membrane-bound pro-TNF-α into soluble TNF-α. Further study demonstrated that the stability of TNF-α mRNA was decreased by hypothemycin treatment. In addition, hypothemycin suppressed LPS-induced phosphorylation of p38 MAPK and ERK. Moreover, knockdown of tristetraprolin (TTP), which is an important trans-acting regulator of TNF-α mRNA stability and downstream target of p38 MAPK and ERK, reversed hypothemycin-mediated inhibition of TNF-α mRNA expression. Collectively, our results suggest that hypothemycin suppresses TNF-α production by TTP-dependent destabilization of TNF-α mRNA and this is mediated, at least in part, by blocking the activation of p38 MAPK and ERK.

Relationship between Menthiafolic Acid and Wine Lactone in Wine.

Menthiafolic acid (6-hydroxy-2,6-dimethylocta-2,7-dienoic acid, 2a) was quantified by GC-MS in 28 white wines, 4 Shiraz wines, and for the first time in 6 white grape juice samples. Menthiafolic acid was detected in all but one of the wine samples at concentrations ranging from 26 to 342 μg/L and in the juice samples from 16 to 236 μg/L. Various model fermentation experiments showed that some menthiafolic acid in wine could be generated from the grape-derived menthiafolic acid glucose ester (2b) during alcoholic and malolactic fermentation. Samples containing high concentrations of menthiafolic acid were also analyzed by enantioselective GC-MS and were shown to contain this compound in predominantly the (S)-configuration. Enantioselective analysis of wine lactone (1) in one of these samples, a four-year-old Chardonnay wine showed, for the first time, the presence of the 3R,3aR,7aS isomer of wine lactone (1b), which is the enantiomer of the form previously reported as the sole isomer present in young wine samples. The weakly odorous 3R,3aR,7aS 1b form comprised 69% of the total wine lactone in the sample. On the basis of the enantioselectivity of the hydrolytic conversion of menthiafolic acid to wine lactone at pH 3.0 determined previously and the relative proportions of (R)- and (S)-menthiafolic acid in the Chardonnay wine, the predicted ratio of wine lactone enantiomers that would be formed from hydrolysis at ambient temperature of the menthiafolic acid present in this wine was close to the ratio measured, which was consistent with menthiafolic acid being the major or sole precursor to wine lactone in this sample.

Antiproliferative Diterpenes from a Malleastrum sp. from the Madagascar dry forest [1

An ethanol extract of leaves of the plant species Malleastrum sp. collected in northern Madagascar afforded the new clerodane diterpene 18-oxo-cleroda-3,13-dien-16,15-olide (1), together with the three known clerodane diterpenes 16,18-dihydroxykolavenic acid lactone (2), solidagolactone (3) and (-)-kolavenol (4), and the known labdane diterpene 3-oxo-ent-Iabda-8(17),13-dien-15,16-olide (5). Compounds 1, 3, and 4 showed moderate antiproliferative activities against the A2780 ovarian cancer cell line, with the IC50 values of 3.01 ± 0.8, 7.84 ± 0.2, and 17.9 ± 3 µM, respectively. The structure elucidations of all compounds were carried out based on analysis of NMR and mass spectroscopic data. The relative stereochemistry of compound 1 was determined by NOESY NMR spectrum.

ChemInform Abstract: Total Syntheses of the Resorcylic Acid Lactone Neocosmosin A and Its Enantiomer.

ChemInformVolume 46, Issue 38 Natural Products ChemInform Abstract: Total Syntheses of the Resorcylic Acid Lactone Neocosmosin A and Its Enantiomer. Yiwen Zhang, Yiwen Zhang Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMichael Dlugosch, Michael Dlugosch Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMartin Juebermann, Martin Juebermann Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMartin G. Banwell, Martin G. Banwell Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorJas S. Ward, Jas S. Ward Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this author Yiwen Zhang, Yiwen Zhang Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMichael Dlugosch, Michael Dlugosch Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMartin Juebermann, Martin Juebermann Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorMartin G. Banwell, Martin G. Banwell Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this authorJas S. Ward, Jas S. Ward Res. Sch. Chem., Aust. Natl. Univ., Canberra, A. C. T. 2601, AustraliaSearch for more papers by this author First published: 03 September 2015 https://doi.org/10.1002/chin.201538213Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume46, Issue38September, 2015 RelatedInformation

ChemInform Abstract: Selective Pyrone Functionalization: Reductive Alkylation of Triacetic Acid Lactone.

AbstractThe reductive alkylation of triacetic acid lactone with aldehydes allows the synthesis of 3‐alkylated derivatives including naturally accruing compound (VI).

Photocatalytic Dehydrogenative Lactonization of 2-Arylbenzoic Acids.

A metal-free dehydrogenative lactonization of 2-arylbenzoic acids at room temperature was developed. This work illustrates the first application of visible-light photoredox catalysis in the preparation of benzo-3,4-coumarins, an important structural motif in bioactive molecules. The combination of photocatalyst [Acr(+)-Mes] with (NH4)2S2O8 as a terminal oxidant provides an economical and environmentally benign entry to different substituted benzocoumarins. Preliminary mechanistic studies suggest that this reaction most likely occurs through a homolytic aromatic substitution pathway.

The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite-Induced Atopic Dermatitis in Nc/Nga Mice.

Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa’s anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa’s properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and IL20Rβ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not IL20Rβ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.