Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Construction of a bicyclic beta-benzyloxy and beta-hydroxy amide library through a multicomponent cyclization reaction.

ABSTRACT: In this manuscript, we describe the synthesis of a bicyclic beta-benzyloxy and beta-hydroxy amide library from cyanohydrin ethers. The benzyloxy amides were prepared through a one-pot sequence of hydrozirconation, acylation, and intramolecular Friedel-Crafts alkylation. Selected benzyl ethers were converted to alcohols by hydrogenolysis in a continuous flow reactor. Chemistry space BCUT metrics and 2D fingerprint similarity calculations showed that these compounds contribute chemical diversity value to existing chemical libraries.

SUBMITTER: Zhang L

PROVIDER: S-EPMC2888746 | biostudies-literature | 2009 Jul-Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Construction of a bicyclic beta-benzyloxy and beta-hydroxy amide library through a multicomponent cyclization reaction.

Zhang Li L Xiao Qing Q Ma Chao C Xie Xiang-Qun XQ Floreancig Paul E PE

Journal of combinatorial chemistry 20090701 4

In this manuscript, we describe the synthesis of a bicyclic beta-benzyloxy and beta-hydroxy amide library from cyanohydrin ethers. The benzyloxy amides were prepared through a one-pot sequence of hydrozirconation, acylation, and intramolecular Friedel-Crafts alkylation. Selected benzyl ethers were converted to alcohols by hydrogenolysis in a continuous flow reactor. Chemistry space BCUT metrics and 2D fingerprint similarity calculations showed that these compounds contribute chemical diversity v ...[more]

PMID: 19505108

Similar Datasets

Construction of a spirooxindole amide library through nitrile hydrozirconation-acylation-cyclization cascade.

Project description:A library of spirooxindoles containing varied elements of structural and stereochemical diversity has been constructed via a three step, one pot nitrile hydrozirconation-acylation-cyclization reaction sequence from common acyclic indole intermediates. The resulting library was evaluated for novelty through comparison with MLSMR and Maybridge compound collections.

| S-EPMC3800499 | biostudies-literature

Controlling Enantioselectivity and Diastereoselectivity in Radical Cascade Cyclization for Construction of Bicyclic Structures.

Project description:Radical cascade cyclization reactions are highly attractive synthetic tools for the construction of polycyclic molecules in organic synthesis. While it has been successfully implemented in diastereoselective synthesis of natural products and other complex compounds, radical cascade cyclization faces a major challenge of controlling enantioselectivity. As the first application of metalloradical catalysis (MRC) for controlling enantioselectivity as well as diastereoselectivity in radical cascade cyclization, we herein report the development of a Co(II)-based catalytic system for asymmetric radical bicyclization of 1,6-enynes with diazo compounds. Through the fine-tuning of D2-symmetric chiral amidoporphyrins as the supporting ligands, the Co(II)-catalyzed radical cascade process, which proceeds in a single operation under mild conditions, enables asymmetric construction of multisubstituted cyclopropane-fused tetrahydrofurans bearing three contiguous stereogenic centers, including two all-carbon quaternary centers, in high yields with excellent stereoselectivities. Combined computational and experimental studies have shed light on the underlying stepwise radical mechanism for this new Co(II)-based cascade bicyclization that involves the relay of several Co-supported C-centered radical intermediates, including α-, β-, γ-, and ε-metalloalkyl radicals. The resulting enantioenriched cyclopropane-fused tetrahydrofurans that contain a trisubstituted vinyl group at the bridgehead, as showcased in several stereospecific transformations, may serve as useful intermediates for stereoselective organic synthesis. The successful demonstration of this new asymmetric radical process via Co(II)-MRC points out a potentially general approach for controlling enantioselectivity as well as diastereoselectivity in synthetically attractive radical cascade reactions.

| S-EPMC8399859 | biostudies-literature

Synthesis of the bicyclic welwitindolinone core via an alkylation/cyclization cascade reaction.

Project description:Synthesis of an advanced welwitindolinone intermediate via an alkylation/cyclization reaction is reported. The key step involves a one pot Lewis acid-mediated alkylation of a silylketene aminal with a furan alcohol followed by an intramolecular cyclization. The reaction is stereoselective and takes place at low temperature. The cycloadduct was highly functionalized and contains the welwitindolinone core structure.

| S-EPMC2784123 | 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

Construction of bicyclic ring systems via a transannular SmI2-mediated ketone-olefin cyclization strategy.

Project description:The development of novel methods and strategies for the formation of polycyclic ring structures is of utmost importance in organic synthesis. The present study describes the investigation of a transannular cyclization strategy for constructing bicyclic ring systems. To test the viability of the approach, the SmI2-mediated ketone-olefin coupling reaction, a method previously developed in this laboratory, was examined. Investigation of the transannular cyclization of cyclooctene, cyclodecene, and cycloundecene derivatives revealed that the process proceeds with high yield and diastereoselectivity, and in the case of larger ring-sized compounds, with excellent regioselectivity. The regioselectivity of the annulation process could be rationalized based on examining the low energy conformations of the keto alkene starting materials. These results demonstrate the efficiency and the potential of the transannular cyclization tactic for the creation of bicyclic ring systems.

| S-EPMC2515389 | biostudies-literature

Synthesis of bicyclic ethers by a palladium-catalyzed oxidative cyclization-redox relay-π-allyl-Pd cyclization cascade reaction.

Project description:Bicyclic ether scaffolds are found in a variety of natural products and are of interest in probe and drug discovery. A palladium-catalyzed cascade reaction has been developed to provide efficient access to these scaffolds from readily available linear diene-diol substrates. A Pd redox-relay process is used strategically to transmit reactivity between an initial oxypalladative cyclization and a subsequent π-allyl-Pd cyclization at remote sites. The reaction affords a variety of bicyclic ether scaffolds with complete diastereoselectivity for cis-ring fusion.

| S-EPMC6601619 | biostudies-literature

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization.

Project description:An operationally simple protocol for the synthesis of 2,3-dihydrobenzo[f][1,4]oxazepin-3-ones, based on an Ugi reaction of an ortho-(benzyloxy)benzylamine, glycolic acid, an isocyanide and an aldehyde, followed by an intramolecular Mitsunobu substitution was developed. The required ortho-(benzyloxy)benzylamines have been in situ generated from the corresponding azides, in turn prepared in high yields from salicylic derivatives.

| S-EPMC3943941 | biostudies-literature

Asymmetric synthesis of tetrahydropyridines via an organocatalytic one-pot multicomponent Michael/aza-Henry/cyclization triple domino reaction.

Project description:A low loading of a quinine-derived squaramide efficiently catalyzes the triple-domino Michael/aza-Henry/cyclization reaction between 1,3-dicarbonyl compounds, ?-nitroolefins, and aldimines to provide tetrahydropyridines bearing three contiguous stereogenic centers in good yields, excellent enantiomeric excesses, and up to high diastereomeric ratios.

| S-EPMC4611353 | biostudies-literature

Diastereoselective synthesis of new zwitterionic bicyclic lactams, scaffolds for construction of 2-substituted-4-hydroxy piperidine and its pipecolic acid derivatives.

Project description:The synthesis of new chiral highly functionalized zwitterionic bicyclic lactams starting from acyclic β-enaminoesters derived from (R)-(-)-2-phenylglycinol is described. The key step involved an intramolecular non-classical Corey-Chaykovsky ring-closing reaction of the corresponding sulfonium salts derived from β-enaminoesters. This methodology permits the generation of two or three new stereogenic centers with high diastereoselectivity. The utility of these intermediates was demonstrated by the stereocontrolled total synthesis of cis-4-hydroxy-2-methyl piperidine and its corresponding pipecolic acid derivative.

| S-EPMC8981097 | biostudies-literature

Synthesis of Benzofuran Derivatives via a DMAP-Mediated Tandem Cyclization Reaction Involving <i>ortho</i>-Hydroxy α-Aminosulfones.

Project description:An efficient cascade cyclization strategy was developed to synthesize aminobenzofuran spiroindanone and spirobarbituric acid derivatives utilizing 2-bromo-1,3-indandione, 5-bromo-1,3-dimethylbarbituric acid, and ortho-hydroxy α-aminosulfones as substrates. Under the optimized reaction conditions, the corresponding products were obtained with high efficiency, exceeding 95% and 85% yields for the respective derivatives. This protocol demonstrates exceptional substrate versatility and robust scalability up to the Gram scale, establishing a stable platform for the synthesis of 3-aminobenzofuran derivative. The successful synthesis paves the way for further biological evaluations with potential implications in scientific research.

| S-EPMC11357171 | 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