Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis-Naphthoquinones.

ABSTRACT: An efficient annulation involving pyrone addition to a quinone and Dieckmann condensation was developed for rapid assembly of a ?-naphthopyrone monomeric precursor to the bis-naphthoquinone natural product aurofusarin. Dimerization was achieved through PdII -catalyzed dehydrogenative coupling. Further studies employing asymmetric nucleophilic epoxidation indicate that the atropisomers of aurofusarin and derivatives are not configurationally stable at ambient temperature.

SUBMITTER: Qi C

PROVIDER: S-EPMC5890919 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Total Synthesis of Aurofusarin: Studies on the Atropisomeric Stability of Bis-Naphthoquinones.

Qi Chao C Wang Wenyu W Reichl Kyle D KD McNeely James J Porco John A JA

Angewandte Chemie (International ed. in English) 20180129 8

An efficient annulation involving pyrone addition to a quinone and Dieckmann condensation was developed for rapid assembly of a γ-naphthopyrone monomeric precursor to the bis-naphthoquinone natural product aurofusarin. Dimerization was achieved through Pd<sup>II</sup> -catalyzed dehydrogenative coupling. Further studies employing asymmetric nucleophilic epoxidation indicate that the atropisomers of aurofusarin and derivatives are not configurationally stable at ambient temperature. ...[more]

PMID: 29318760

Similar Datasets

Enantioselective total synthesis and studies into the configurational stability of bismurrayaquinone A.

Project description:Lost in rotation: the concise strategy of the first enantioselective total synthesis of bismurrayaquinone A utilized traceless stereochemical exchange to form an enantioenriched biphenyl core that was elaborated in a bidirectional manner to the natural product. Observed racemization on an unsuccessful initial route prompted studies into the configurational stability of bismurrayaquinone A and related biquinones.

| S-EPMC3517045 | biostudies-literature

Bidirectional enantioselective synthesis of bis-benzofuran atropisomeric oligoarenes featuring two distal C-C stereogenic axes.

Project description:We report the bidirectional enantioselective synthesis of bis-benzofuran atropisomeric oligoarenes featuring two distal C-C stereogenic axes obtained by a two-fold central-to-axial chirality conversion upon oxidative aromatization. The key enantioenriched centrally chiral bis-dihydrobenzofuran precursors were synthesized via a bidirectional diastereo- and enantio-selective organocatalyzed domino reaction between simple achiral and easily accessible dihydroxylated aromatics and chloronitroalkenes. Moreover, the stereodivergent nature of the methodology was established by synthesizing both diastereomers of a non-symmetrically functionalized bis-axially chiral oligoarene.

| S-EPMC7021203 | biostudies-literature

Synthesis, leishmanicidal activity and theoretical evaluations of a series of substituted bis-2-hydroxy-1,4-naphthoquinones.

Project description:A series of eight substituted bis-2-hydroxy-1,4-naphthoquinone derivatives was synthesized through lawsone condensation with various aromatic and aliphatic aldehydes under mild acidic conditions. The title compounds were evaluated for antileishmanial activity in vitro against Leishmania amazonensis and Leishmania braziliensis promastigotes; six compounds showed good activity without significant toxic effects. The compound with the highest activity was used for an in vivo assay with Leishmania amazonensis.

| S-EPMC6271274 | biostudies-literature

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits.

Project description:A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1'-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation.

| S-EPMC5684547 | biostudies-literature

Synthesis of Amino Acid-Naphthoquinones and In Vitro Studies on Cervical and Breast Cell Lines.

Project description:We performed an extensive analysis about the reaction conditions of the 1,4-Michael addition of amino acids to 1,4-naphthoquinone and substitution to 2,3-dichloronaphthoquinone, and a complete evaluation of stoichiometry, use of different bases, and the pH influence was performed. We were able to show that microwave-assisted synthesis is the best method for the synthesis of naphthoquinone-amino acid and chloride-naphthoquinone-amino acid derivatives with 79-91% and 78-91% yields, respectively. The cyclic voltammetry profiles showed that both series of naphthoquinone-amino acid derivatives mainly display one quasi-reversible redox reaction process. Interestingly, it was shown that naphthoquinone derivatives possess a selective antitumorigenic activity against cervix cancer cell lines and chloride-naphthoquinone-amino acid derivatives against breast cancer cell lines. Furthermore, the newly synthetized compounds with asparagine-naphthoquinones (3e and 4e) inhibited ~85% of SiHa cell proliferation. These results show promising compounds for specific cervical and breast cancer treatment.

| S-EPMC6930466 | biostudies-literature

Catalyst-Controlled Stereodivergent Synthesis of Atropisomeric Multiaxis Systems.

Project description:Molecular scaffolds with multiple rotationally restricted bonds allow a precise spatial positioning of functional groups. However, their synthesis requires methods addressing the configuration of each stereogenic axis. We report here a catalyst-stereocontrolled synthesis of atropisomeric multiaxis systems enabling divergence from the prevailing stereochemical reaction path. By using ion-pairing catalysts in arene-forming aldol condensations, a strong substrate-induced stereopreference can be overcome to provide structurally well-defined helical oligo-1,2-naphthylenes. The configuration of up to four stereogenic axes was individually catalyst-controlled, affording quinquenaphthalenes with a unique topology.

| S-EPMC5968508 | biostudies-literature

Metabolic Stability of New Mito-Protective Short-Chain Naphthoquinones.

Project description:Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which significantly restricts is therapeutic activity. Therefore, this study assessed the metabolic stability of the 16 identified naphthoquinone derivatives 1-16 using hepatocarcinoma cells in combination with an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed significantly better stability than idebenone over 6 h (p < 0.001). By extending the side-chain of SCQs, increased stability for some compounds was observed. Metabolic conversion from the derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed. These results highlight the therapeutic potential of naphthoquinone-based SCQs and provide essential insights for future drug design, prodrug therapy, and polytherapy, respectively.

| S-EPMC7169385 | biostudies-literature

Enantioselective synthesis of atropisomeric benzamides through peptide-catalyzed bromination.

Project description:We report the enantioselective synthesis of atropisomeric benzamides employing catalytic electrophilic aromatic substitution reactions involving bromination. The catalyst is a simple tetrapeptide bearing a tertiary amine that may function as a Brønsted base. A series of tri- and dibrominations were accomplished for a range of compounds bearing differential substitution patterns. Tertiary benzamides represent appropriate substrates for the reaction since they exhibit sufficiently high barriers to racemization after ortho functionalization. Mechanism-driven experiments provided some insight into the basis for selectivity. Examination of the observed products at low conversion suggested that the initial catalytic bromination may be regioselective and stereochemistry-determining. A complex between the catalyst and substrate was observed by NMR spectroscopy, revealing a specific association. Finally, the products of these reactions may be subjected to regioselective metal-halogen exchange and trapping with I(2), setting the stage for utility.

| S-EPMC3596792 | biostudies-literature

Practical Organocatalytic Synthesis of Functionalized Non-C2-Symmetrical Atropisomeric Biaryls.

Project description:An organic acid catalyzed direct arylation of aromatic C(sp(2))-H bonds in phenols and naphthols for the preparation of 1,1'-linked functionalized biaryls was developed. The products are non-C2-symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98?mmol), and the structurally diverse 2,2'-dihydroxy biaryl (i.e., BINOL-type), as well as 2-amino-2'-hydroxy products (i.e., NOBIN-type) are formed with complete regioselectivity. Density-functional calculations suggest that the quinone and imino-quinone monoacetal coupling partners are exclusively arylated at their ?-position by an asynchronous [3,3]-sigmatropic rearrangement of a mixed acetal species which is formed in?situ under the reaction conditions.

| S-EPMC4824624 | biostudies-literature

Anticancer activity and SAR studies of substituted 1,4-naphthoquinones.

Project description:In this paper, we report the structure-activity relationship studies of substituted 1,4-naphthoquinones for its anticancer properties. 1,4-Naphthoquinone, Juglone, Menadione, Plumbagin and LLL12.1 were used as lead molecules to design PD compounds. Most of the PD compounds showed improved antiproliferative activity in comparison to the lead molecule in prostate (DU-145), breast (MDA-MB-231) and colon (HT-29) cancer cell lines. PD9, PD10, PD11, PD13, PD14 and PD15 were found to be the most potent compound with an IC? value of 1-3 ?M in all cancer cell lines. Fluorescent polarization assay was employed to study the inhibition of STAT3 dimerization by PD compounds. PD9 and PD18 were found to be potent STAT3 dimerization inhibitors.

| S-EPMC4304211 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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