Browse
Submit Data
Databases
API
Help

Dataset Information

26 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Asymmetric Synthesis of Homocitric Acid Lactone.

ABSTRACT: A short, diastereoselective synthesis of homocitric acid lactone is described. The key step is a bioinspired aldol addition to set the stereogenic center in an intermediate that requires only modest oxidation state manipulation to complete the synthesis. This approach enables rapid generation of isotopomers in which carbon and hydrogen can be replaced by heavier nuclei at nearly every position.

SUBMITTER: Nickerson LA

PROVIDER: S-EPMC7190193 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Asymmetric Synthesis of Homocitric Acid Lactone.

Nickerson Leslie A LA Huynh Valerie V Balmond Edward I EI Cramer Stephen P SP Shaw Jared T JT

The Journal of organic chemistry 20161021 22

A short, diastereoselective synthesis of homocitric acid lactone is described. The key step is a bioinspired aldol addition to set the stereogenic center in an intermediate that requires only modest oxidation state manipulation to complete the synthesis. This approach enables rapid generation of isotopomers in which carbon and hydrogen can be replaced by heavier nuclei at nearly every position. ...[more]

PMID: 27685496

Similar Datasets

Enantioselective synthesis of isotopically labeled homocitric acid lactone.

Project description:A concise synthesis of homocitric acid lactone was developed to accommodate systematic placement of carbon isotopes (specifically (13)C) for detailed studies of this cofactor. This new route uses a chiral allylic alcohol, available in multigram quantities from enzymatic resolution, as a starting material, which transposes asymmetry through an Ireland-Claisen rearrangement.

| S-EPMC3932135 | biostudies-literature

Synthesis of novel beta-lactone inhibitors of fatty acid synthase.

Project description:Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.

| S-EPMC3172131 | biostudies-literature

Asymmetric Synthesis of <i>N</i>,<i>O</i>-Heterobicyclic Octanes and (-)-Geissman-Waiss Lactone.

Project description:A short, asymmetric synthesis of tetrahydro-2H-furo[3,2-b]pyrrole derivatives and (-)-Geissman-Waiss lactone starting from meso-cyclohexadiene epoxide is described. Pivotal transformations in the developed synthetic procedure include asymmetric epoxide ring opening to install the requisite 1S,5S stereocenters and oxidative lactonization/lactamization sequences. This route provides a streamlined synthetic pathway toward necine alkaloids.

| S-EPMC8482504 | biostudies-literature

Catalytic Asymmetric Total Synthesis of (-)-Actinophyllic Acid.

Project description:Described herein is a catalytic asymmetric total synthesis of (-)-actinophyllic acid, with the key step being a chiral phosphine-catalyzed [3 + 2] annulation between an imine and an allenoate to form a pyrroline intermediate in 99% yield and 94% ee. The synthesis also features CuI-catalyzed coupling between a ketoester and a 2-iodoindole to shape the tetrahydroazocine ring; intramolecular alkylative lactonization; SmI2-mediated intramolecular pinacol coupling between ketone and lactone subunits to assemble the complex skeleton of (-)-actinophyllic acid; and an unprecedented regioselective dehydroxylation.

| S-EPMC4920546 | biostudies-literature

Bioengineering triacetic acid lactone production in Yarrowia lipolytica for pogostone synthesis.

Project description:Yarrowia lipolytica is an oleaginous yeast that is recognized for its ability to accumulate high levels of lipids, which can serve as precursors to biobased fuels and chemicals. Polyketides, such as triacetic acid lactone (TAL), can also serve as a precursor for diverse commodity chemicals. This study used Y. lipolytica as a host organism for the production of TAL via expression of the 2-pyrone synthase gene from Gerbera hybrida. Induction of lipid biosynthesis by nitrogen-limited growth conditions increased TAL titers. We also manipulated basal levels of TAL production using a DNA cut-and-paste transposon to mobilize and integrate multiple copies of the 2-pyrone synthase gene. Strain modifications and batch fermentation in nitrogen-limited medium yielded TAL titers of 2.6 g/L. Furthermore, we show that minimal medium allows TAL to be readily concentrated at >94% purity and converted at 96% yield to pogostone, a valuable antibiotic. Modifications of this reaction scheme yielded diverse related compounds. Thus, oleaginous organisms have the potential to be flexible microbial biofactories capable of economical synthesis of platform chemicals and the generation of industrially relevant molecules.

| S-EPMC6855914 | biostudies-literature

Reactions of Trifluorotriacetic Acid Lactone and Hexafluorodehydroacetic Acid with Amines: Synthesis of Trifluoromethylated 4-Pyridones and Aminoenones.

Project description:Dehydroacetic acid and triacetic acid lactone are known to be versatile substrates for the synthesis of a variety of azaheterocycles. However, their fluorinated analogs were poorly described in the literature. In the present work, we have investigated reactions of trifluorotriacetic acid lactone and hexafluorodehydroacetic acid with primary amines, phenylenediamine, and phenylhydrazine. While hexafluorodehydroacetic acid reacted the same way as non-fluorinated analog giving 2,6-bis(trifluoromethyl)-4-pyridones, trifluorotriacetic acid lactone had different regioselectivity of nucleophilic attack compared to the parent structure, and corresponding 3-amino-6,6,6-trifluoro-5-oxohex-3-eneamides were formed as the products. In the case of binucleophiles, further cyclization took place, forming corresponding benzodiazepine and pyrazoles. The obtained 2,6-bis(trifluoromethyl)-4-pyridones were able to react with active methylene compounds giving fluorinated merocyanine dyes.

| S-EPMC9610390 | biostudies-literature

Asymmetric Total Synthesis of 19,20-Epoxydocosapentaenoic Acid, a Bioactive Metabolite of Docosahexaenoic Acid.

Project description:In this study, we report the first asymmetric total synthesis of 19,20-epoxydocosapentaenoic acid (19,20-EDP), a naturally occurring bioactive cytochrome P450 metabolite of docosahexaenoic acid, a major constituent of fish oil. Our strategy involves direct asymmetric epoxidation to produce an enantiopure β-epoxyaldehyde that can be appended to the rest of the skipped polyene core by Wittig condensation. Our route is step-economical and late divergent and could be an appealing method by which to synthesize EDP analogues for biological studies.

| S-EPMC7944941 | biostudies-literature

Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone.

Project description:Searching for the new anticancer compounds we prepared three new β-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17⁻99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC50 in the range 22.8⁻33.9 µg/mL).

| S-EPMC6412764 | biostudies-literature

Lewis Acid Enabled Copper-Catalyzed Asymmetric Synthesis of Chiral ?-Substituted Amides.

Project description:Here we report that readily available silyl- and boron-based Lewis acids in combination with chiral copper catalysts are able to overcome the reactivity issues of unactivated enamides, known as the least reactive carboxylic acid derivatives, toward alkylation with organomagnesium reagents. Allowing unequaled chemo-reactivity and stereocontrol in catalytic asymmetric conjugate addition to enamides, the method is distinguished by its unprecedented reaction scope, allowing even the most challenging and synthetically important methylations to be accomplished with good yields and excellent enantioselectivities. This catalytic protocol tolerates a broad temperature range (-78 °C to ambient) and scale up (10 g), while the chiral catalyst can be reused without affecting overall efficiency. Mechanistic studies revealed the fate of the Lewis acid in each elementary step of the copper-catalyzed conjugate addition of Grignard reagents to enamides, allowing us to identify the most likely catalytic cycle of the reaction.

| S-EPMC5639465 | biostudies-literature

Asymmetric Synthesis of Griffipavixanthone Employing a Chiral Phosphoric Acid-Catalyzed Cycloaddition.

Project description:Asymmetric synthesis of the biologically active xanthone dimer griffipavixanthone is reported along with its absolute stereochemistry determination. Synthesis of the natural product is accomplished via dimerization of a p-quinone methide using a chiral phosphoric acid catalyst to afford a protected precursor in excellent diastereo- and enantioselectivity. Mechanistic studies, including an unbiased computational investigation of chiral ion-pairs using parallel tempering, were performed in order to probe the mode of asymmetric induction.

| S-EPMC6475489 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data