Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi-Mumm and regiospecific quinazolinone rearrangements.

ABSTRACT: An efficient four-step, six-transformation protocol was developed to afford bioactive N-alkyl- or N-arylamide (E)-arylamidines featuring strategic amidine C3 modifications which were inaccessible or low yielding by previous methods. This synthetic approach, exemplified with 24 amidines and requiring only a single purification, highlights a multicomponent Ugi-Mumm rearrangement to afford highly diversified quinazolinones which undergo regiospecific rearrangement to afford new amidines. The method extensively broadens the structural scope of this new class of trisubstituted amidines and demonstrates the tolerance of regional C3 amidine steric bulk, visualized with X-ray crystallographic analysis.

SUBMITTER: Jaffett VA

PROVIDER: S-EPMC6426674 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi-Mumm and regiospecific quinazolinone rearrangements.

Jaffett Victor A VA Nerurkar Alok A Cao Xufeng X Guzei Ilia A IA Golden Jennifer E JE

Organic & biomolecular chemistry 20190301 12

An efficient four-step, six-transformation protocol was developed to afford bioactive N-alkyl- or N-arylamide (E)-arylamidines featuring strategic amidine C3 modifications which were inaccessible or low yielding by previous methods. This synthetic approach, exemplified with 24 amidines and requiring only a single purification, highlights a multicomponent Ugi-Mumm rearrangement to afford highly diversified quinazolinones which undergo regiospecific rearrangement to afford new amidines. The method ...[more]

PMID: 30730519

Similar Datasets

Facile One-Pot Synthesis of Functionalized Quinoline-Fused Fluorescent Dihydro/Spiro-quinazolinone Derivatives.

Project description:A facile and efficient method has been developed for the synthesis of quinoline-fused fluorescent dihydro/spiro-quinazolinones. A plausible mechanism involving an acid-mediated enaminone intermediate is provided. The reaction proceeded using p-toluene sulfonic acid as a green promoter. The methodology was successful in synthesizing various quinoline-appended spiro-quinazolinones 4a-o. The synthetic utility of compounds 4a-o was demonstrated by synthesizing compounds 6a-d via Suzuki coupling as a key reaction. Significantly, the π-π* electronic transition of compounds 4c and 4k showed a blue shift. The molar extinction coefficient (ε), Stoke's shift (Δu̅), and quantum yield (Φf)c were calculated for these derivatives (4c and 4k).

| S-EPMC9219092 | biostudies-literature

Genomic rearrangements in C3 glomerulopathies

Project description:Copy number variations and genomic rearrangements in the CFH-CFHRs region were assessed with a custom-designed high-density 8x15k oligonucleotide CGH arrays spanning the RCA gene cluster region in human chromosome 1q32 (median resolution of 110 bp) (AMADID 040193, Agilent Technologies, Santa Clara, CA). A healthy male donor sample, fully genotyped for that region, was used as hybridization control. Microarray data were extracted and visualized using the Feature Extraction Software v10.7 and Genomic Workbench Standard Edition 7.0 (Agilent Corp, Santa Clara, CA). Copy number altered regions were detected using ADM-2 (set as 5) statistic provided by DNA Analytics, with a minimum number of 5 consecutive probes. Genomic build hg19 was used for the experiment.

2013-05-28 | GSE45585 | GEO

Genomic rearrangements in C3 glomerulopathies

2013-05-28 | E-GEOD-45585 | biostudies-arrayexpress

Regiospecific Hetero-Assembly of DNA-Functionalized Plasmonic Upconversion Superstructures.

Project description:We report a novel strategy for regiospecific hetero-assembly of DNA-modified gold nanoparticles (DNA-AuNPs) onto upconversion nanoparticles (UCNPs) into hybrid lab-on-a-particle systems. The DNA-AuNPs have been assembled onto the hexagonal plate-like UCNPs with well-regulated stoichiometry and controlled organization onto the different facets of UCNP, forming various addressable superstructures. The fine-tuning of stoichiometry and organization is realized by biorecognition specificity of DNA toward specific crystal facets of UCNPs. Such a hetero-assembled DNA-AuNP/UCNP system maintains both plasmonic resonance of AuNPs and fluorescent properties of UCNPs, allowing targeted dual-modality imaging of cancer cells using an aptamer.

| S-EPMC4677663 | biostudies-literature

Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones.

Project description:Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.

| S-EPMC6615762 | biostudies-literature

Synthesis of a boron-containing amidoxime reagent and its application to synthesize functionalized oxadiazole and quinazolinone derivatives.

Project description:Herein, we report the design, synthesis and application of a borylated amidoxime reagent for the direct synthesis of functionalized oxadiazole and quinazolinone derivatives. This reagent exhibits broad synthetic utility to obtain a variety of biologically relevant drug-like molecules. It can be easily prepared at large scale from relatively inexpensive reagents, and can undergo facile transformations to obtain target compounds. The developed amidoxime reagent was synthesized from 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile and hydroxyl amine hydrochloride using N,N-diisopropylethylamine as a base in ethanol under reflux conditions. Overall advantages include a metal-free route to boronated oxadiazoles, quinazolinone derivatives, and restriction of the multistep sequences. Importantly, the boron-rich pharmacophore derived compounds were obtained through an efficient and inexpensive strategy.

| S-EPMC9348647 | biostudies-literature

Regiospecific Photochemical Synthesis of Methylchrysenes.

Project description:Methylated polycyclic aromatic hydrocarbons (PAHs) are suspected to be some of the toxic compounds in crude oil towards marine life and are needed as single compounds for environmental studies. 1-, 3- and 6-methylchrysene (3a,b,c) were prepared as single isomers by photochemical cyclization of the corresponding stilbenoids in the Mallory reaction using stoichiometric amounts of iodine in 82-88% yield. 2-methylchrysene (3d) was prepared by photochemical cyclization where the regioselectivity was controlled by elimination of an ortho-methoxy group under acidic oxygen free conditions in 72% yield. These conditions failed to form 4-methylchrysene from the corresponding stilbenoid. All stilbenoids were made from a common naphthyl Wittig salt and suitably substituted benzaldehydes. We have also demonstrated that methylchrysenes can be oxidized to the corresponding chrysenecarboxylic acids by KMnO4 in modest yields.

| S-EPMC9822284 | 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

Improved synthesis of 15-deoxyspergualin analogs using the Ugi multi-component reaction.

Project description:Spergualin is a natural product that exhibits immunosuppressive, anti-tumor and anti-bacterial activities. Its derivatives, such as 15-deoxyspergualin (15-DSG), have been clinically approved for acute allograft rejection. However, the reported syntheses are cumbersome (>10 steps) and they suffer from low overall yields (?0.3% to 18%). Moreover, spergualin and its derivatives are chemically unstable and rapidly hydrolyzed in aqueous buffer. Here, we have re-explored these issues and report a modified synthetic route with significantly improved overall yield (?31% to 47%). The key transformation is a microwave-accelerated Ugi multi-component reaction that is used to generate the peptoid core in a single step. Using the products of this route, we found that modifications of the hemiaminal significantly increased chemical stability. Thus, we anticipate that this synthetic route will improve access to biologically active 15-DSG derivatives.

| S-EPMC3088103 | biostudies-literature

Three-Step Telescoped Synthesis of Monosubstituted Vicinal Diamines from Aldehydes.

Project description:Aldehydes are easily transformed into vicinal diamines and piperazines through a one-pot procedure including a Darzens reaction and treatment with an amine or diamine and then with a reducing agent. Additionally, quinoxalines can be accessed by reaction with 1,2-benzenediamine under oxidative conditions. These transformations are simple methods for the preparation of synthetically interesting monosubstituted diamines, piperazines, and quinoxalines.

| S-EPMC6648690 | 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