Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multicomponent Petasis Reaction for the Synthesis of Functionalized 2-Aminothiophenes and Thienodiazepines.

ABSTRACT: Multicomponent Petasis reaction has been widely applied for the synthesis of functionalized amine building blocks and biologically active compounds. Employing primary aromatic amines that are not typical reactive substrates contributes to expand the application scope of the Petasis reaction. In this study, we demonstrated the synthesis of functionalized 2-aminothiophenes using Gewald-reaction-derived 2-aminothiophenes as the amine substrates, whose low reactivity in the Petasis reaction was overcome using hexafluoro-2-propanol as the solvent in a mild condition. The obtained Petasis products are amenable for further transformations owing to the presence of multiple functional handles. A following intramolecular cyclization of selected Petasis products afforded substituted tricyclic heterocycles that incorporate a pharmaceutically interesting thienodiazepine moiety.

SUBMITTER: Hwang J

PROVIDER: S-EPMC7584359 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Multicomponent Petasis Reaction for the Synthesis of Functionalized 2-Aminothiophenes and Thienodiazepines.

Hwang Jimin J Borgelt Lydia L Wu Peng P

ACS combinatorial science 20200928 10

Multicomponent Petasis reaction has been widely applied for the synthesis of functionalized amine building blocks and biologically active compounds. Employing primary aromatic amines that are not typical reactive substrates contributes to expand the application scope of the Petasis reaction. In this study, we demonstrated the synthesis of functionalized 2-aminothiophenes using Gewald-reaction-derived 2-aminothiophenes as the amine substrates, whose low reactivity in the Petasis reaction was over ...[more]

PMID: 32985878

Similar Datasets

Photoredox-Catalyzed Multicomponent Petasis Reaction with Alkyltrifluoroborates.

Project description:A redox-neutral alkyl Petasis reaction has been developed that proceeds via photoredox catalysis. A diverse set of primary, secondary, and tertiary alkyltrifluoroborates participate effectively in this reaction through a single-electron transfer mechanism, in contrast to the traditional two-electron Petasis reaction, which accommodates only unsaturated boronic acids. This protocol is ideal to diversify benzyl-type and glyoxalate-derived aldehydes, anilines, and alkyltrifluoroborates toward the rapid assembly of libraries of higher molecular complexity important in pharmaceutical and agrochemical settings.

| S-EPMC7086342 | biostudies-literature

Photoredox-catalyzed multicomponent Petasis reaction in batch and continuous flow with alkyl boronic acids.

Project description:Multicomponent reactions (MCRs) are ideal platforms for the generation of a wide variety of organic scaffolds in a convergent and atom-economical manner. Many strategies for the generation of highly substituted and diverse structures have been developed and among these, the Petasis reaction represents a viable reaction manifold for the synthesis of substituted amines via coupling of an amine, an aldehyde and a boronic acid (BA). Despite its synthetic utility, the inherent drawbacks associated with the traditional two-electron Petasis reaction have stimulated continuous research towards more facile and tolerant methodologies. In this regard, we present the use of free alkyl BAs as effective radical precursors in this MCR through a single-electron transfer mechanism under mild reaction conditions. We have further demonstrated its applicability to photo-flow reactors, facilitating the reaction scale-up for the rapid assembly of complex molecular structures.

| S-EPMC8487034 | biostudies-literature

A Bronsted Acid-Catalyzed Multicomponent Reaction for the Synthesis of Highly Functionalized γ-Lactam Derivatives.

Project description:Brønsted acids catalyze a multicomponent reaction of benzaldehyde with amines and diethyl acetylenedicarboxylate to afford highly functionalized γ-lactam derivatives. The reaction consists of a Mannich reaction of an enamine to an imine, both generated in situ, promoted by a phosphoric acid catalyst and a subsequent intramolecular cyclization. The hydrolysis of the cyclic enamine substrate can provide enol derivatives and, moreover, a second attack of the amine on the carboxylate can afford amide derivatives. An optimization of the reaction conditions is presented in order to obtain selectively cyclic enamines that can afford the enol species after selective hydrolysis.

| S-EPMC6719937 | biostudies-literature

Multicomponent reaction discovery: three-component synthesis of spirooxindoles.

Project description:The Lewis acid-catalyzed, three-component reaction of isatin and two 1,3-dicarbonyl compounds is reported. Reactions proceed with high efficiency under mild reaction conditions and with good functional group tolerance to afford spirooxindole pyranochromenedione derivatives.

| S-EPMC2814073 | biostudies-literature

Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono-Mannich Reaction.

Project description:Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein-protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite all-carbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki-Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product. Our final synthetic sequence employs a diastereoselective Petasis borono-Mannich reaction to couple eburnamine to a trifluoroborate aspidospermidine derivative. These convergent approaches enabled the synthesis of eight diastereomers of this heterodimer and offer support for the reassignment of the absolute configuration of strempeliopidine.

| S-EPMC10281614 | biostudies-literature

Ugi Multicomponent Reaction Based Synthesis of Medium-Sized Rings.

Project description:An Ugi multicomponent reaction based two-step strategy was applied to generate medium-sized rings. In the first linear expansion phase, a series of diamines reacted with cyclic anhydrides to produce different lengths of terminal synthetic amino acids as the starting material for the second phase. The Ugi-4-center 3-component reaction was utilized to construct complex medium-sized rings (8-11) by the addition of isocyanides and oxo components. This method features mild conditions and a broad substrate scope.

| S-EPMC5698880 | biostudies-literature

Multicomponent Reaction Based Synthesis of 1-Tetrazolylimidazo[1,5- a]pyridines.

Project description:A series of unprecedented tetrazole-linked imidazo[1,5- a]pyridines are synthesized from simple and readily available building blocks. The reaction sequence involves an azido-Ugi-deprotection reaction followed by an acetic anhydride-mediated N-acylation-cyclization process to afford the target heterocycle. Furthermore, the scope of the methodology was extended to diverse R3-substitutions by employing commercial anhydrides, acid chlorides, and acids as an acyl component. The scope for the postmodification reactions are explored and the usefulness of the synthesis is exemplified by an improved three-step synthesis of a guanylate cyclase stimulator.

| S-EPMC6038091 | biostudies-literature

Synthesis of Stimuli-Responsive Heterofunctional Dendrimer by Passerini Multicomponent Reaction.

Project description:We report the synthesis of a structurally diverse amphiphilic dendrimer with oxidation and ultraviolet light-sensitive groups incorporated in the dendrimer interior. Convergent synthesis is utilized by reacting branched repeating units with a nonbranched functional molecule by two synthetic strategies, Passerini multicomponent reaction and azide-alkyne cycloaddition reaction. The periphery of dendrimer was functionalized by methoxy poly(ethylene glycol) to obtain a dendrimer with a hydrophobic core and hydrophilic peripheral chains. The G2-PEG dendrimer characterized by NMR, GPC, and MALDI-TOF MS for structural integrity and oxidation- and photo-triggered degradations of the G2-PEG dendrimer was investigated. The self-assembled morphology of the dendrimer in the presence of organic dye was also investigated by TEM and DLS analyses, together with dissipative particle dynamics simulation. The encapsulation of dye molecules in self-assembled nanospheres of the dendrimer and their responsive releases, triggered by the efficient disassembly of a dendrimer, have been demonstrated.

| S-EPMC6648294 | biostudies-literature

Synthesis of Carfentanil Amide Opioids Using the Ugi Multicomponent Reaction.

Project description:We report a novel approach to synthesize carfentanil amide analogues utilizing the isocyanide-based four-component Ugi multicomponent reaction. A small library of bis-amide analogues of carfentanil was created using N-alkylpiperidones, aniline, propionic acid, and various aliphatic isocyanides. Our lead compound showed high affinity for mu (MOR) and delta opioid receptors (DOR) with no appreciable affinity for kappa (KOR) receptors in radioligand binding assays. The compound was found to be a mixed MOR agonist/partial DOR agonist in [(35)S]GTPγS functional assays, and it showed moderate analgesic potency in vivo. The compound showed no visible signs of physical dependence or constipation in mice. In addition, it produced less respiratory depression than morphine. Most mixed MOR/DOR opioids reported in the literature are peptides and thereby systemically inactive. Our approach utilizing a multicomponent reaction has the promise to deliver potent and efficacious small-molecule analgesics with potential clinical utility.

| S-EPMC4641535 | biostudies-literature

Cysteine Isocyanide in Multicomponent Reaction: Synthesis of Peptido-Mimetic 1,3-Azoles.

Project description:An alternative approach toward the simple and robust synthesis of highly substituted peptidic thiazole derivatives using Ugi-multicomponent reaction (U-MCR) is described. Thus, we introduced the enantiopure (R)-2-methyl-2-isocyano-3-(tritylthio)propanoate as a novel class of isocyanide in MCR. This bifunctional isocyanide was found to undergo mild cyclodehydration to afford thiazole containing peptidomimetics in a short synthetic sequence. Several examples of bis-heterocyclic rings were also synthesized through the proper choice of the aldehyde component in the U-4CR. The method opens a wide range of applications toward the synthesis of nonribosomal natural products and other bioactive compounds.

| S-EPMC5603900 | 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