Heteroaromatic Cation‐Based Chromophores: Synthesis and Nonlinear Optical Properties of Alkynylazinium Salts

Cañeque, Tatiana; Cuadro, Ana M.; Alvárez‐Builla, Julio; Pérez‐Moreno, Javier; Clays, Koen; Marcelo, Gema; Mendicuti, Francisco; Castaño, Obis; Andrés, José M.; Vaquero, Juan J.

doi:10.1002/ejoc.201000816

Cited by 13 publications

(6 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…mp: 163-165 °C (lit. [286] In accordance with previously reported data. [286] 3-Bromo-N-methylquinolinium iodide (115) Following the general procedure, the title compound was prepared from 3-bromoquinoline (67b) (0.33 mL, 2.40 mmol), CH 3 I (0.75 mL, 12.00 mmol) in CH 3 CN (25 mL).…”

Section: -Bromo-n-methylpyridinium Iodide (121)supporting

confidence: 92%

“…[286] In accordance with previously reported data. [286] 3-Bromo-N-methylquinolinium iodide (115) Following the general procedure, the title compound was prepared from 3-bromoquinoline (67b) (0.33 mL, 2.40 mmol), CH 3 I (0.75 mL, 12.00 mmol) in CH 3 CN (25 mL). After refluxing for 22 hours, workup was carried out according to the general procedure to give the target compound 115 as a bright yellow powder (835.3 mg, 99%).…”

Section: -Bromo-n-methylpyridinium Iodide (121)supporting

confidence: 92%

See 1 more Smart Citation

Divergent Synthesis of Indolo[3,2- c]quinolines, Neocryptolepines and Related Tetracyclic Ring-Systems Containing Promising Biological Activities

Håheim¹

2022

View full text Add to dashboard Cite

Malaria is a devastating tropical disease, claiming approximately 627 000 lives in 2020. Due to the appearance of resistance towards artemisinin-based therapies, the discovery of novel treatments are of paramount importance. The indoloquinoline natural products cryptolepine, neocryptolepine and isocryptolepine, first discovered in the extracts of the African bush plant Cryptolepis sanguinolenta, have been found to exhibit potent antimalarial properties. More- over, several functionalized derivatives of these compounds have shown great promise as an- tiplasmodial agents. The indoloquinoline alkaloids have also been found to possess significant antiproliferative and antimicrobial properties, making them ideal targets for the development into novel drug candidates. The first project in this work details the application of a synthetic approach first devel- oped by Helgeland and Sydnes to assemble various tetracyclic ring systems. The key synthetic strategies being a Suzuki-Miyaura cross-coupling reaction followed by a palladium-catalyzed intramolecular cyclization. Though the approach was unsuitable to construct all the intended target molecules, it furnished the unexpected pyridophenanthridine scaffold. By further inves- tigating alternative protocols for the construction of indoloquinolines, a regiodivergent inter- mediate was discovered, which allowed for the synthesis of both novel pyridophenanthridine and pyridocarbazole scaffolds by utilizing two different reaction protocols. By subjecting this common intermediate to a diazotization-azidation-nitrene insertion approach, the novel pyrido- carbazoles could be furnished in excellent yields. The unexpected formation of a biquinoline bridged by an aniline during a Suzuki-Miyaura cross-coupling reaction, was deemed interesting for development into a transition metal com- plex for catalysis. Through a collaborative effort with Dr. Eugene Khaskin’s group at Oki- nawa Institute of Science and Technology, five quinoline/pyridine N,N,N ligands were designed and synthesized. The key synthetic tools utilized in their construction was either a sequential Suzuki-Miyaura cross-coupling reaction and Buchwald-Hartwig amination or reductive amina- tion. A novel two-step approach for the synthesis of the natural product neocryptolepine from commercially available bromoquinolines was developed. The key transformations being re- gioselective N-alkylations followed by a cascade Suzuki-Miyaura cross-coupling reaction and intramolecular nucleophilic C-N bond formation. The scope and limitations for the novel pro- tocol was evaluated through the preparation of 24 neocryptolepine derivatives, bearing a diverse range of functional groups, where electron-withdrawing group substitutions were generally su- perior. It became apparent that it would also be possible to prepare a library of indolo[3,2-c]quino- lines from the same starting material as the newly devised strategy to produce neocryptolepines. By utilizing a reaction sequence consisting of a Suzuki-Miyaura cross-coupling reaction, in- stallation of an azido moiety and finally photochemical cyclization, this goal was realized, producing a total of 19 indoloquinolines. This protocol was less robost towards substrate func- tionalizations than the neocryptolepine approach, with no apparent trend concerning electron- withdrawing and electron-donating groups being apparent. The photochemical cyclization was hypothesized to proceed via the formation of a reactive singlet nitrene intermediate. Finally, a selection of the prepared tetracyclic compounds assembled during this work was evaluated for their antiplasmodial, antiproliferative and antimicrobial activities by the help of various external collaborators. The most successful compound was revealed to be the novel pyridophenanthridines, displaying more potent antiproliferative activities than doxoru- bicin against human prostate cancer (IC50 = 24 nM). The novel pyridocarbazoles moreover showed excellent inhibition of biofilm formation, with the potential to be developed into a dual anticancer-antimicrobial agent. Of all the tested compounds, only N-methylated pyridocar- bazole was found to contain any significant activity against the evaluated Plasmodium falci- parum strain. The antimicrobial assays revealed the importance of the inclusion of a methyl group for activity, but not strictly in the form of an N-methyl unit, which is the general con- census in the literature thus far. Further, chlorinated indoloquinolines were revealed to contain excellent antimicrobial activity against both Gram-positive and Gram-negative bacterial cell lines.

show abstract

Section: -Bromo-n-methylpyridinium Iodide (121)supporting

confidence: 92%

Section: -Bromo-n-methylpyridinium Iodide (121)supporting

confidence: 92%

Divergent Synthesis of Indolo[3,2- c]quinolines, Neocryptolepines and Related Tetracyclic Ring-Systems Containing Promising Biological Activities

Håheim¹

2022

View full text Add to dashboard Cite

show abstract

“…Polycyclic cationic hetarenes have recently attracted much interest with regard to their synthesis and applications. Specifically, quinolizinium‐type derivatives with a bridgehead quaternary nitrogen atom (azoniahetarenes) figure as promising lead structures for the development of DNA‐binding and DNA‐photodamaging agents, enzyme inhibitors, cystic fibrosis transmembrane conductance regulator activators, fluorescent dyes and chemosensors, or nonlinear optical materials . As a result, several synthetic routes have been developed and explored for the synthesis of substituted or annelated quinolizinium derivatives .…”

Section: Introductionmentioning

confidence: 99%

Studies on the photocyclization reaction of 8‐styryl‐substituted coralyne derivatives

Pithan

Ihmels

2020

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

The photoreactivity of four 8‐styryl‐substituted coralyne derivatives was examined by UV/VIS‐ and 1H‐NMR‐spectroscopy. Except for the dimethylamino‐substituted derivative, these cationic azoniaheterocyclic dyes undergo photocyclization that most likely proceeds through an initial E‐Z‐isomerization of the double bond. Subsequent oxidation of the intermediates under aerobic conditions gave the pyrrolo‐annelated quinolizinium derivatives as final products, thus providing a useful synthetic route to polycyclic azoniahetarene derivatives. The 6‐(4‐chlorophenyl)‐substituted pyrroloquinolizinium derivative was isolated on a preparative scale, and the investigation of its photophysical properties revealed significantly red‐shifted absorption (λabs = 465–480 nm) and emission bands (λfl = 550–562 nm) in comparison to the parent coralyne and the styryl‐substituted derivatives.

show abstract

“…BOX ligands were prepared as described in the literature. 21 Alkynes 6j , 22 6q , 23 6r , 24 6s , 25 6v , 26 6w , 27 and 6x 28 were prepared as described in the literature.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Copper-Catalyzed Alkynylation of Benzopyranyl Oxocarbenium Ions

et al. 2015

View full text Add to dashboard Cite

We have developed highly enantioselective, copper-catalyzed alkynylations of benzopyranyl acetals. By using a copper(I) catalyst equipped with a chiral bis(oxazoline) ligand, high yields and enantioselectivities are achieved in the alkynylation of widely available, racemic isochroman and chromene acetals to deliver α-chiral oxygen heterocycles. This method demonstrates that chiral organometallic nucleophiles can be successfully used in enantioselective additions to oxocarbenium ions.

show abstract

Heteroaromatic Cation‐Based Chromophores: Synthesis and Nonlinear Optical Properties of Alkynylazinium Salts

Cited by 13 publications

References 45 publications

Divergent Synthesis of Indolo[3,2- c]quinolines, Neocryptolepines and Related Tetracyclic Ring-Systems Containing Promising Biological Activities

Divergent Synthesis of Indolo[3,2- c]quinolines, Neocryptolepines and Related Tetracyclic Ring-Systems Containing Promising Biological Activities

Studies on the photocyclization reaction of 8‐styryl‐substituted coralyne derivatives

Enantioselective Copper-Catalyzed Alkynylation of Benzopyranyl Oxocarbenium Ions

Contact Info

Product

Resources

About