Quinolizine Derivatives Research Articles

Syntheses of Tetracyclic Indoline Derivatives Via Gold(I)-Catalyzed Hydroamination/Cycloisomerization Cascade of 2-Ethynyltryptamides.

A gold(I)-catalyzed hydroamination/cycloisomerization cascade reaction was developed to yield indolizino[8,7-b]indole and indolo[2,3-a]-quinolizine derivatives from 2-ethynyltryptamides. The optimal conditions were determined by condition screening, and the functional group tolerances of these reactions were explored based on synthetic substrates. An insight into the explanation on the selectivity of the ring closure was obtained by density functional theory calculations. A plausible mechanism for the cascade reactions was proposed. Derivatization of the indolizino[8,7-b]indole and total synthesis of nauclefidine demonstrated the practicality of this strategy.

Intramolecular [2 + 2] Cycloaddition of Isocarbostyrils Catalyzed by an Iridium Visible-Light Photocatalyst.

Irradiation on N-(ω-alkenyl)isocarbostyrils in the presence of an iridium photocatalyst by LEDs emitting 455 nm light gave the corresponding cyclobutane-fused benzo[b]quinolizine derivatives stereoselectively in high yields. Loading 1 mol % of the catalyst was enough to obtain high yields of the products in convenient reaction time in many cases. The reaction likely proceeds through stepwise [2 + 2] cycloaddition via a triplet biradical intermediate.

Connecting two intrinsic electron donor and acceptor moieties through distinctive π-bridging units to explore their optical and nonlinear optical properties

Boraphenalene and pyrido(2,1,6-de)quinolizine moieties are intrinsically electron acceptor and donor groups, owing to their electron deficient and electron rich characteristics, respectively. In the current study, quantum computations are executed for investigating the charge transfer character and nonlinear optical (NLO) response for various combinations of boraphenalene and pyrido(2,1,6-de)quinolizine derivatives. The effect of various π-conjugated connectors i.e. direct ring attachment (1AB), ethylene (2AB), acetylene (3AB) and phenylene (4AB) units on optical and NLO properties were studied. Density functional theory (DFT) techniques are employed for computing the responses properties for designed compounds (A, B, 1AB, 2AB, 3AB and 4AB). From the studied compounds, 4AB exhibits the leading average second-order NLO polarizability of 954.8 × 10-30 esu, which was about 148 times greater than para-Nitroaniline (p-NA) molecule (a typical push-pull NLO molecule). The source of greater values of hyperpolarizability is tracked through TD-DFT computations where electronic transitions having better oscillator strengths along with lower transition energies are seen more contributing in hyperpolarizability. Additionally, the assessment of electrostatic potentials (ESPs), density of states (DOS), frontier molecular orbitals (FMOs) and transition density matrix (TDM) diagrams provide a molecular-level insight into the structures and their relationship to NLO properties of designed derivatives. Hence, the current investigation would arouse the curiosity of other scientists in the field for such different and novel strategy for designing NLO materials.

Anthraquinolone and quinolizine derivatives as an alley of future treatment for COVID-19: an in silico machine learning hypothesis

Coronavirus disease 2019 (Covid-19), caused by novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has come to the fore in Wuhan, China in December 2019 and has been spreading expeditiously all over the world due to its high transmissibility and pathogenicity. From the outbreak of COVID-19, many efforts are being made to find a way to fight this pandemic. More than 300 clinical trials are ongoing to investigate the potential therapeutic option for preventing/treating COVID-19. Considering the critical role of SARS-CoV-2 main protease (Mpro) in pathogenesis being primarily involved in polyprotein processing and virus maturation, it makes SARS-CoV-2 main protease (Mpro) as an attractive and promising antiviral target. Thus, in our study, we focused on SARS-CoV-2 main protease (Mpro), used machine learning algorithms and virtually screened small derivatives of anthraquinolone and quinolizine from PubChem that may act as potential inhibitor. Prioritisation of cavity atoms obtained through pharmacophore mapping and other physicochemical descriptors of the derivatives helped mapped important chemical features for ligand binding interaction and also for synergistic studies with molecular docking. Subsequently, these studies outcome were supported through simulation trajectories that further proved anthraquinolone and quinolizine derivatives as potential small molecules to be tested experimentally in treating COVID-19 patients.

Gold(i)-catalyzed pathway-switchable tandem cycloisomerizations to indolizino[8,7-b]indole and indolo[2,3-a]quinolizine derivatives.

Experimental and theoretical explorations were performed on the pathways of the cascade cycloisomerizations of tryptamine-N-ethynylpropiolamide substrates. The methodology provided a common strategy to access either indolizino[8,7-b]indoles or indolo[2,3-a]quinolizines in a switchable fashion.

ChemInform Abstract: An Efficient One‐Pot Three‐Component Process for Synthesis of Perfluoroalkylated Quinolizines.

A facile multi-component process for the synthesis of perfluoroalkylated quinolizine derivatives was achieved using various arylidenemalononitriles, pyridine, and methyl perfluoroalk-2-ynoates as starting materials. Moderate yields were obtained under mild condition. The structures of perfluoroalkylated quinolizine derivatives were characterized by means of 1H NMR, 13C NMR, 19F NMR, IR, LRMS and HRMS. Furthermore, the reaction mechanism was proposed.

An Efficient One‐pot Three‐component Process for Synthesis of Perfluoroalkylated Quinolizines

AbstractA facile multi‐component process for the synthesis of perfluoroalkylated quinolizine derivatives was achieved using various arylidenemalononitriles, pyridine, and methyl perfluoroalk‐2‐ynoates as starting materials. Moderate yields were obtained under mild condition. The structures of perfluoroalkylated quinolizine derivatives were characterized by means of 1H NMR, 13C NMR, 19F NMR, IR, LRMS and HRMS. Furthermore, the reaction mechanism was proposed.

ChemInform Abstract: Diastereoselective Synthesis of Highly Functionalized Quinolizines via a Pyridine‐Based Three‐Component Reaction and a DFT Investigation on the Reaction Mechanism.

AbstractThis novel, one‐pot, three‐component reaction affords quinolizine derivatives via 1,4‐dipolar cycloaddition without using any catalyst or activation.

ChemInform Abstract: A β‐Enaminone‐Initiated Multicomponent Domino Reaction for the Synthesis of Indoloquinolizines and Benzoquinolizines from Acyclic Precursors.

The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two CC and two CN bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet–Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet–Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.

A β‐Enaminone‐Initiated Multicomponent Domino Reaction for the Synthesis of Indoloquinolizines and Benzoquinolizines from Acyclic Precursors

The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,β-unsaturated aldehydes, and β-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two C-C and two C-N bonds by a domino process comprising initial β-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet-Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet-Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.

ChemInform Abstract: Three‐Component Reactions Involving Quinoline or Isoquinoline, Dialkyl Acetylenedicarboxylate and β‐Trifluoroacetyl Vinyl Ethyl Ether.

Abstract The three-component reactions (TCRs) involving quinoline or isoquinoline, dialkyl acetylenedicarboxylate and β-trifluoroacetyl vinyl ethyl ether were investigated. The reaction proceeded smoothly under ambient temperature in DMSO to give the 4-trifluoroacetyl substituted benzo[c]quinolizine derivatives in moderate yields. However, under the same reaction condition, isoquinoline afforded the 2-trifluoromethyl substituted 1-oxa-(11H)-benzo[a]dihydroquinolizine or 4-trifluoroacetyl substituted benzo[a]dihydroquinolizine products. The possible reaction pathways were proposed.

ChemInform Abstract: Synthesis of Fluorescent Pyrrolo[3,4‐b]quinolizine Derivatives and Evaluations as a Protein‐Labeling Probe.

AbstractThe new fluorescent compounds (III), (V), (VII), and (VIII) are synthesized via an one‐pot condensation reaction.

Three-component reactions involving quinoline or isoquinoline, dialkyl acetylenedicarboxylate and β-trifluoroacetyl vinyl ethyl ether

The three-component reactions (TCRs) involving quinoline or isoquinoline, dialkyl acetylenedicarboxylate and β-trifluoroacetyl vinyl ethyl ether were investigated. The reaction proceeded smoothly under ambient temperature in DMSO to give the 4-trifluoroacetyl substituted benzo[c]quinolizine derivatives in moderate yields. However, under the same reaction condition, isoquinoline afforded the 2-trifluoromethyl substituted 1-oxa-(11H)-benzo[a]dihydroquinolizine or 4-trifluoroacetyl substituted benzo[a]dihydroquinolizine products. The possible reaction pathways were proposed.

Synthesis of Fluorescent Pyrrolo[3,4-b]quinolizine Derivatives and Evaluation as a Protein-Labeling Probe

Synthesis of Fluorescent Pyrrolo[3,4-b]quinolizine Derivatives and Evaluation as a Protein-Labeling Probe

Novel Synthesis of 4H‐Quinolizine Derivatives Using Sulfonyl Ketene Dithioacetals

AbstractIn the synthesis of 4H‐quinolizine derivatives involving the use of a sulfonyl ketene dithioacetal, we found a novel reaction in which the remaining methylsulfanyl group was replaced with a proton after the ring‐closure reaction in the quinolizine skeleton under mild conditions, without the use of any metallic reagent. The reaction of 3,3‐bis(methylsulfanyl)‐2‐phenylsulfonylacrylonitriles (1a,b) with 2‐pyridylacetonitrile (2a) in the presence of potassium carbonate as a base in DMSO afforded 4‐imino‐2‐methylsulfanyl‐3‐phenylsulfonyl‐4H‐quinolizine‐1‐carbonitriles (3a,b). The methylsulfanyl group at the 2‐position of 3a,b was readily removed under methanol reflux conditions to afford 4‐imino‐3‐phenylsulfonyl‐4H‐quinolizine‐1‐carbonitriles (4a,b) in good yields. Alkyl 3‐phenylsulfonyl‐4H‐quinolizine‐1‐carboxylates (4c–f) were directly synthesized from sulfonyl ketene dithioacetal (1a,b) with alkyl 2‐pyridylacetates (2b,c) and involved desulfanylation by simple hydrolysis. In addition, the fluorescent properties of these compounds were investigated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

ChemInform Abstract: Synthesis of Quinolizino[3,2‐a]quinolizine Derivatives and Their Fluorescence.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Quinolizino[3,2-a]quinolizine Derivatives and Their Fluorescence

Polycyclic quinolizine derivatives, quinolizino[3,2-a]quinolizines (4a-c), were synthesized in moderate yields by a one-pot method using ketene dithioacetal, methyl bis(methylsulfanyl)methylene-cyanoacetate (2), alkyl 2-pyridylacetates (1a, b), and 2-pyridylacetonitrile (1c). Compounds 4a, b exhibited red fluorescence (Em max: 576 nm) in solid state.

A New Synthesis of Bis-Enaminones via Acylation of Ketones

A short and efficient synthesis for a series of 1,6-diaryl- 3,4-diarylaminohexa-2,4-diene-1,6-diones was developed. Based on the acylation-prototropism sequence during the reaction of vari- ous aryl methyl ketones with bis-imidoyl chlorides, the products were isolated in good yields. Substituted acetophenones, acetyl- thiophene, 3-acetylpyridine, and acetylferrocene can be integrated into this reaction as ketone component. Similarly, a-tetralone can be transformed with bis-electrophiles into the corresponding bis- enaminones. Treatment of 2-acetylpyridine with N,N¢-bis(4- tolyl)ethanebis(imidoyl) dichloride yielded not only the expected bis-enaminone, but also a new quinolizine derivative which was structurally characterized by single crystal X-ray analysis. Analo- gously, pinacolone and cyclopropyl methyl ketone can readily be converted into bis-enaminones. Monoimidoyl chlorides showed the same reactivity, providing derivatives in high yields.

Synthesis of pyrano[4,3-b]quinolizine derivatives from 6-aryl or styryl-4-methylsulfanyl-2-oxo-2H-pyrans and their fluorescence

New fluorescent compounds 1,11-dihydro-11-imino-1-oxo-3-phenylpyrano[4,3-b]quinolizines were synthesized in good yields by the reaction of 6-aryl-3-cyano-4-methylsulfanyl-2H-pyrones and 4-methylsulfanyl-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile with 2-pyridylacetates. These fused quinolizine derivatives exhibited fluorescence in solid and solution states.

Synthesis of Fused Quinolizine Derivatives by Condensation of Cyclic Schiff Bases with β-Keto Esters

A new procedure has been developed for the synthesis of fused nitrogen-containing heterocycles having a bridgehead nitrogen atom via condensation of cyclic Schiff bases with β-keto esters.