4363-94-4

Usage

Uses

Used in Pharmaceutical Industry:
6-Methoxyquinoline-4-carbaldehyde is used as a key intermediate in the synthesis of various pharmaceutical compounds. Its ability to react with other molecules makes it a valuable building block for creating new drugs with specific therapeutic properties.
Used in Synthesis of Bacterial Topoisomerase Inhibitors:
6-Methoxyquinoline-4-carbaldehyde is used as a reactant for the synthesis of tetrahydropyran-based bacterial topoisomerase inhibitors. These inhibitors are essential in the development of new antibiotics, as they target and disrupt the function of bacterial topoisomerases, which are crucial for bacterial DNA replication and transcription. By inhibiting these enzymes, the compound can help in the development of novel treatments for bacterial infections, particularly those resistant to existing antibiotics.

InChI:InChI=1/C11H9NO2/c1-14-9-2-3-11-10(6-9)8(7-13)4-5-12-11/h2-7H,1H3

Upstream product

• 41037-26-7 6-methoxy-4-methylquinoline 
• 67-56-1 methanol 
• 5949-29-1 citric acid monohydrate 
• 6119-47-7 quinine monohydrochloride dihydrate 
• 42881-66-3 4-bromo-6-methoxyquinoline 
• 68-12-2 N,N-dimethyl-formamide 
• 4295-04-9 4-chloro-6-methoxyquinoline 
• 23432-39-5 4-hydroxy-6-methoxyquinoline 
• 25063-43-8 2,2-dimethyl-5-(((4-methoxyphenyl)amino)methylene)-1,3-dioxane-4,6-dione 
• 105104-88-9 2-(6-methoxyquinolin-4-yl)ethanol 
• 104-94-9 4-methoxy-aniline 

Downstream Products

• 911319-42-1 (3R,5R,6S)-3-[(R)-Hydroxy-(6-methoxy-quinolin-4-yl)-methyl]-2-oxo-5,6-diphenyl-morpholine-4-carboxylic acid benzyl ester 
• 911319-63-6 (3R,5R,6S)-3-[(R)-(6-Methoxy-quinolin-4-yl)-triethylsilanyloxy-methyl]-5,6-diphenyl-morpholin-2-one 
• 911319-64-7 (2R,3R)-2-((1R,2S)-2-Hydroxy-1,2-diphenyl-ethylamino)-3-(6-methoxy-quinolin-4-yl)-3-triethylsilanyloxy-propionic acid methyl ester 
• 911319-66-9 (1R,2R)-6-benzyloxy-2-tert-butoxycarbonylamino-3-oxo-1-(6-methoxyquinol-4-yl)-1-triethylsilyloxy-hexane 
• 911319-71-6 Benzoic acid (E)-4-{(2S,3S)-3-hydroxy-2-[(R)-(6-methoxy-quinolin-4-yl)-triethylsilanyloxy-methyl]-piperidin-1-yl}-but-2-enyl ester 
• 911319-51-2 (2R)-1-[(E)-4-benzoyloxy-2-butenyl]-2-[(R)-6-methoxyquinol-4-yl-triethylsilyloxy]methyl-3-oxo-piperidine 
• 911319-45-4 (1R,2S,3R)-6-benzyloxy-2-tert-butoxycarbonylamino-3-hydroxy-1-(6-methoxyquinol-4-yl)-1-triethylsilyloxy-hexane 

Relevant academic research and scientific papers

Synthetic ferrocenic mefloquine and quinine analogues as potential antimalarial agents

A few years ago we proposed a strategy for the synthesis of new ferrocene-chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic ferrocenyl moieties. Now, this strategy has been applied to the antimalarial amino-alcohols class to afford new potentially active analogues of mefloquine and quinine bearing a substituted ferrocenic group. The pathway used for the synthesis of the mefloquine analogues includes the coupling of an aminomethyl substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the other hand, the synthesis of quinine analogues was ensured by the 'inverse' reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The configurations of each diastereoisomer were unambiguously determined by spectroscopic data. The mechanistic interpretations were fully discussed. Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial activity than mefloquine and quinine themselves. Comparing optical isomers, those isomers dissimilar to ferrocenyl derivatives presented better antimalarial activities than those similar to ferrocenyl. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

Metal-Free Chemoselective Oxidation of 4-Methylquinolines into Quinoline-4-Carbaldehydes

A convenient protocol for the synthesis of quinoline-4-carbaldehydes via chemoselective oxidation of 4-methylquinolines using hypervalent iodine(III) reagents as oxidant is described. This method highlights metal-free and mild reaction conditions, nice yield, good functional group tolerance, and high chemoselectivity.

Direct access of the chiral quinolinyl core of cinchona alkaloids via a br?nsted acid and chiral amine co-catalyzed chemo- and enantioselective α-alkylation of quinolinylmethanols with enals

A strategy for the facile construction of the chiral quinolinylmethanolic structure, a core featured in cinchona alkaloids, is reported. A new reactivity is harnessed by TfOH-promoted chemoselective activation of α-C-H over O-H bond in quinolinylmethanols. The new reactivity is successfully engineered with an iminium catalysis in a synergistic manner to create a powerful conjugate addition-cyclization cascade process for synthesis of chiral quinoline derived π-butyrolactones in good yields and with good to excellent enantioselectivities. The method enables the first total synthesis of natural product broussonetine in three steps.

Design, synthesis, and characterization of novel tetrahydropyran-based bacterial topoisomerase inhibitors with potent anti-gram-positive activity

There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential

The design, synthesis, in silico ADME profiling, antiplasmodial and antimycobacterial evaluation of new arylamino quinoline derivatives

A series of new arylamino quinoline derivatives was designed based on the quinine and mefloquine scaffolds and evaluated in vitro for antiplasmodial and antimycobacterial activities. A number of these compounds exhibited significant activity against the d

Scope of stereoselective Mn-mediated radical addition to chiral hydrazones and application in a formal synthesis of quinine

Stereocontrolled Mn-mediated addition of alkyl iodides to chiral N-acylhydrazones enables strategic C-C bond constructions at the stereogenic centers of chiral amines. Applying this strategy to quinine suggested complementary synthetic approaches to construct C-C bonds attached at the nitrogen-bearing stereogenic center using multifunctional alkyl iodides 6a-d as radical precursors, or using multifunctional chiral N-acylhydrazones 26a-d as radical acceptors. These were included among Mn-mediated radical additions of various alkyl iodides to a range of chiral N-acylhydrazone radical acceptors, leading to the discovery that pyridine and alkene functionalities are incompatible. In a revised strategy, these functionalities are avoided during the Mn-mediated radical addition of 6d to chiral N-acylhydrazone 22b, which generated a key C-C bond with complete stereochemical control at the chiral amine carbon of quinine. Subsequent elaboration included two sequential cyclizations to complete the azabicyclo[2.2.2]octane ring system. Group selectivity between two 2-iodoethyl groups during the second cyclization favored an undesired azabicyclo[3.2.1]octane ring system, an outcome that was found to be consistent with transition state calculations at the B3LYP/6-31G(d) level. Group differentiation at an earlier stage enabled an alternative regioconvergent pathway; this furnished the desired azabicyclo[2.2.2]octane ring system and afforded quincorine (21b), completing a formal synthesis of quinine.

Intermolecular radical addition to N-acylhydrazones as a stereocontrol strategy for alkaloid synthesis: Formal synthesis of quinine

Stereocontrolled Mn-mediated radical addition of alkyl iodides to chiral N-acylhydrazones enables strategic C-C bond disconnection of chiral amines. This strategy was examined in the context of a total synthesis of quinine, generating new findings of functional group compatibility leading to a revised strategy. Completion of a formal synthesis of quinine is presented, validating the application of Mn-mediated radical addition as a useful new C-C bond construction method for alkaloid synthesis. The Mn-mediated addition generates the chiral amine substructure of quinine with complete stereocontrol. Subsequent elaboration includes two successive ring closures to forge the azabicyclo[2.2.2]octane ring system of quincorine, linked to quinine through two known reactions.

The hydroxyl functionality and a rigid proximal N are required for forming a novel non-covalent quinine-heme complex

Quinoline antimalarial drugs bind both monomeric and dimeric forms of free heme, with distinct preferences depending on the chemical environment. Under biological conditions, chloroquine (CQ) appears to prefer to bind to μ-oxo dimeric heme, while quinine (QN) preferentially binds monomer. To further explore this important distinction, we study three newly synthesized and several commercially available QN analogues lacking various functional groups. We find that removal of the QN hydroxyl lowers heme affinity, hemozoin (Hz) inhibition efficiency, and antiplasmodial activity. Elimination of the rigid quinuclidyl ring has similar effects, but elimination of either the vinyl or methoxy group does not. Replacing the quinuclidyl N with a less rigid tertiary aliphatic N only partially restores activity. To further study these trends, we probe drug-heme interactions via NMR studies with both Fe and Zn protoporphyrin IX (FPIX, ZnPIX) for QN, dehydroxyQN (DHQN), dequinuclidylQN (DQQN), and deamino-dequinuclidylQN (DADQQN). Magnetic susceptibility measurements in the presence of FPIX demonstrate that these compounds differentially perturb FPIX monomer-dimer equilibrium. We also isolate the QN-FPIX complex formed under mild aqueous conditions and analyze it by mass spectrometry, as well as fluorescence, vibrational, and solid-state NMR spectroscopies. The data elucidate key features of QN pharmacology and allow us to propose a refined model for the preferred binding of QN to monomeric FPIX under biologically relevant conditions. With this model in hand, we also propose how QN, CQ, and amodiaquine (AQ) differ in their ability to inhibit Hz formation.

From serendipity to rational antituberculosis drug discovery of mefloquine-isoxazole carboxylic acid esters

Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported antituberculosis activity is rapidly converted to two metabolites 3

Synthetic studies on quinine: Quinuclidine construction via a ketone enolate regio- and diastereoselective Pd-mediated allylic alkylation

7-Hydroxy-quinine was synthesized by an asymmetric aldol reaction that establishes the C8 and C9 stereochemistry, followed by construction of the 3-vinyl-quinuclidine azabicyclo[2.2.2]octane by C3-C4 ring closure using an intramolecular palladium-mediated