Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Mechanochemical Aza-Vinylogous Povarov Reactions for the Synthesis of Highly Functionalized 1,2,3,4-Tetrahydroquinolines and 1,2,3,4-Tetrahydro-1,5-Naphthyridines.

ABSTRACT: The aza-vinylogous Povarov reaction between aromatic amines, α-ketoaldehydes or α-formylesters and α,β-unsaturated dimethylhydrazones was carried out in a sequential three-component fashion under mechanochemical conditions. Following extensive optimization work, the reaction was performed on a vibratory ball mill operating at 20 Hz and using zirconium oxide balls and milling jar, and afforded 1,2,3,4-tetrahydroquinolines and 1,2,3,4-tetrahydro- 1,5-naphthyridines functionalized at C-2, C-4 and also at C-6, in the latter case. This protocol generally afforded the target compounds in good to excellent yields and diastereoselectivities. A comparison of representative examples with the results obtained under conventional conditions revealed that the mechanochemical protocol affords faster Povarov reactions in comparable yields using a solvent-less environment.

SUBMITTER: Clerigue J

PROVIDER: S-EPMC7958332 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

1,2,3,4-Tetrahydro-1,5-naphthyridines and related heterocyclic scaffolds: Exploration of suitable chemistry for library development.

Project description:The chemistry of 1,2,3,4-tetrahydro-1,5-naphthyridines and 2,3,4,5-tetrahydro-1H-pyrido[3,2-b]azepines has been explored with the goal of discovering reactions at N1 suitable for library development. Epoxide openings, palladium-catalyzed N-arylations, DEPBT-promoted acylations, and urea formation through the reaction with isocyanates were all successful. The epoxide opening chemistry using homochiral epichlorohydrin, with epoxide reclosure and a second nucleophilic opening led to the preparation of a small 24-membered library.

| S-EPMC2608727 | biostudies-literature

Facile synthesis of functionalized tetrahydroquinolines via domino Povarov reactions of arylamines, methyl propiolate and aromatic aldehydes.

Project description:In the presence of p-toluenesulfonic acid as catalyst the domino reaction of arylamines, methyl propiolates and aromatic aldehydes in ethanol proceeded smoothly to give polysubstituted 1,2,3,4-tetrahydroquinolines in moderate yields. The reaction is believed to involve the Povarov reaction of in situ generated β-enamino ester with the in situ formed aromatic imine.

| S-EPMC3511020 | biostudies-literature

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner-Wadsworth-Emmons-based approach.

Project description:Integrin inhibitors based on the tripeptide sequence Arg-Gly-Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner-Wadsworth-Emmons olefination, diimide reduction, and global deprotection to synthesise cores for these compounds in high yields (63-83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps.

| S-EPMC7356399 | biostudies-literature

Aza-Annulation of 1,2,3,4-Tetrahydro-β-carboline Derived Enaminones and Nitroenamines: Synthesis of Functionalized Indolizino[8,7-b]indoles, Pyrido[1,2-a:3,4-b']diindoles, Indolo[2,3-a]quinolizidine-4-ones and Other Tetrahydro-β-carboline Fused Heterocycles.

Project description:Aza-annulation of novel 1,2,3,4-tetrahydro-β-carboline derived enaminones and nitroenamines with various 1,2- and 1,3-bis electrophiles, such as oxalyl chloride, maleic anhydride, 1,4-benzoquinone, 3-bromopropionyl chloride, itaconic anhydride, and imines (from formaldehyde and primary amines), has been investigated. These methodologies provide simple one-step pathways for efficient construction of highly functionalized tetrahydro-β-carboline 1,2-fused, five- and six-membered heterocyclic frameworks, such as indolizino[8,7-b]indoles, pyrido[1,2-a:3,4-b']diindoles, indolo[2,3-a]quinolizidines, and pyrimido[1',6':1,2]pyrido[3,4-b]indoles, which are core structures of many naturally occurring indole alkaloids with diverse bioactivity.

| S-EPMC6822222 | biostudies-literature

Antibacterial activity of quinoxalines, quinazolines, and 1,5-naphthyridines.

Project description:Several phenyl substituted naphthalenes and isoquinolines have been identified as antibacterial agents that inhibit FtsZ-Zing formation. In the present study we evaluated the antibacterial of several phenyl substituted quinoxalines, quinazolines and 1,5-naphthyridines against methicillin-sensitive and methicillin-resistant Staphylococcusaureus and vancomycin-sensitive and vancomycin-resistant Enterococcusfaecalis. Some of the more active compounds against S. aureus were evaluated for their effect on FtsZ protein polymerization. Further studies were also performed to assess their relative bactericidal and bacteriostatic activities. The notable differences observed between nonquaternized and quaternized quinoxaline derivatives suggest that differing mechanisms of action are associated with their antibacterial properties.

| S-EPMC3947850 | biostudies-literature

Gold-Catalyzed Hydroalkoxylation/Povarov Reaction Cascade of Alkynols with N-Aryl Imines: Synthesis of Tetrahydroquinolines.

Project description:A one-pot gold-catalyzed hydroalkoxylation/Povarov reaction cascade of alkynols with N-aryl imines or in situ generated iminium has been developed. The protocol provides a facile access to a series of fused tricyclic tetrahydroquinolines with a broad substrate scope using readily available materials under mild conditions. The unique mechanistic feature is the dual function of the gold catalyst, which first catalyzed the intramolecular hydroalkoxylation of alkynols, and upon the formation of dihydrofuran species, promoted the following Povarov reaction with high stereoselectivity.

| S-EPMC6761745 | biostudies-literature

Optimization of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines as tubulin polymerization inhibitors.

Project description:Thirteen new N-aryl 1,2,3,4-tetrahydroquinoline compounds (4a-f, 6a-c, and 8a-d) were synthesized and evaluated for antitumor activity and drug-like properties. Compound 4a exhibited high inhibitory potency with low nanomolar GI50 values of 16-20 nM in cellular assays, including excellent activity against the P-glycoprotein overexpressing cell line KBvin. Compound 4a inhibited colchicine binding to tubulin and tubulin assembly with an IC50 value of 0.85 ?M, superior to the reference compound CA4 (1.2 ?M) in the same assay. In addition, 4a also exhibited highly improved water solubility (75 ?g/mL) and a suitable logP value (3.43) at pH 7.4. With a good balance between antitumor potency and drug-like properties, compound 4a could be a new potential drug candidate for further development. Current results on SAR studies and molecular modeling provided more insight about this class of compounds as tubulin polymerization inhibitors targeting the colchicine site.

| S-EPMC4554882 | biostudies-literature

2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.

Project description:A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors.

| S-EPMC2275803 | biostudies-literature

1,2,3,4-Tetrahydro-1,4,5,8-tetraazaanthracene revisited: properties and structural evidence of aromaticity loss.

Project description:The synthesis and properties of 1,2,3,4-tetrahydro-1,4,5,8-tetraazaanthracene (THTAA) - a heterocycle involving both >N-H donating and =N- accepting moieties - have been reinvestigated. Unlike previously reported, THTAA is a thermally stable compound that can be re-sublimed at 300-310 °C without decomposition. Controlled introduction of substituents at the nitrogen atoms of THTAA led to variation of its electron donor/acceptor capability that allowed fine-tuning the absorption properties. The propensity of these compounds and a number of its derivatives to form infinite chains involving >N-H···N= and >N-H···Hal-···N+ atoms is demonstrated by X-ray structure analysis. The DFT level optimized and experimental geometry of THTAA and its derivatives show considerable loss of aromaticity within the quinoxaline moiety.

| S-EPMC6720741 | biostudies-literature

Ethyl 2-(1,2,3,4-tetrahydro-spiro-[carba-zole-3,2'-[1,3]dioxolan]-9-yl)acetate.

Project description:In the title compound, C(18)H(21)NO(4), the hydrogenated six-membered ring of the carbazole unit adopts a half-chair conformation. The dioxolane ring and ethyl-acetate substituent point to opposite sides of the carbazole plane. The ethyl-acetate substituent adopts an essentially fully extended conformation, and its mean plane forms a dihedral angle of 83.8 (1)° with respect to the carbazole mean plane. The mol-ecules are arranged into stacks in which the carbazole planes form a dihedral angle of 4.4 (1)° and have an approximate inter-planar separation of 3.6 Å.

| S-EPMC2969037 | 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