Formation of Pyridazinium Salts by Azo Coupling of <i>N</i>‐Substituted 3‐Amino‐1‐phenylbut‐2‐en‐1‐ones and Diazonium Salts

Šimůnek, Petr; Pešková, Markéta; Bertolasi, Valerio; Lyčka, Antonı́n; Macháček, Vladimı́r

doi:10.1002/ejoc.200400287

Cited by 15 publications

(6 citation statements)

References 31 publications

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“…This connection was confirmed by the observation of splitting the 1 H- 15 N HMBC spectrum in the F1 dimension (S8 Fig), which is caused by coupling between the two nitrogen atoms in the molecule. The coupling constant ( 1 JNN = 17 Hz) agrees with the previously reported one-bond couplings between nitrogens [26–28]. The nitrogen atom N-2 shows correlation with the H-6 hydrogen belonging to the spin system A, which integrates the six-membered heterocyclic core of NoA.…”

Section: Resultssupporting

confidence: 88%

The cyanobacterial metabolite nocuolin a is a natural oxadiazine that triggers apoptosis in human cancer cells

Voráčová¹,

Hájek²,

Mareš³

et al. 2017

PLoS ONE

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Oxadiazines are heterocyclic compounds containing N-N-O or N-N-C-O system within a six membered ring. These structures have been up to now exclusively prepared via organic synthesis. Here, we report the discovery of a natural oxadiazine nocuolin A (NoA) that has a unique structure based on 1,2,3-oxadiazine. We have identified this compound in three independent cyanobacterial strains of genera Nostoc, Nodularia, and Anabaena and recognized the putative gene clusters for NoA biosynthesis in their genomes. Its structure was characterized using a combination of NMR, HRMS and FTIR methods. The compound was first isolated as a positive hit during screening for apoptotic inducers in crude cyanobacterial extracts. We demonstrated that NoA-induced cell death has attributes of caspase-dependent apoptosis. Moreover, NoA exhibits a potent anti-proliferative activity (0.7–4.5 μM) against several human cancer lines, with p53-mutated cell lines being even more sensitive. Since cancers bearing p53 mutations are resistant to several conventional anti-cancer drugs, NoA may offer a new scaffold for the development of drugs that have the potential to target tumor cells independent of their p53 status. As no analogous type of compound was previously described in the nature, NoA establishes a novel class of bioactive secondary metabolites.

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Section: Resultssupporting

confidence: 88%

The cyanobacterial metabolite nocuolin a is a natural oxadiazine that triggers apoptosis in human cancer cells

Voráčová¹,

Hájek²,

Mareš³

et al. 2017

PLoS ONE

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“…im nek et al [48] observed 1 J( 15 N, 15 N) = 10.6 Hz for the nitrogens of the =NNHC 6 H 5 fragment in 4-dimethyl-5-(phenyldiazenyl)pent-4-en-2,3-dione 3-phenylhydrazone and utilized the 1 J( 15 N, 15 N) coupling constants [49] to determine the nitrogen-nitrogen connectivity in 4-(2,4-dimethoxyphenylamino)-1-phenyl-5-phenyldiazenyl-6-phenylpyridazinium tetrafluoroborate ( 1 J( 15 N, 15 [50], 2h J( 19 F, 15 N) in a hydrogen-bonded FH-collidine complex [51,52], 2h J( 15 N, 13 C) and 2h J( 31 P, 15 N) [53], 3h J( 31 P, 15 N) coupling constants across N-H…O-P hydrogen bonds [54], 2h J( 35 Cl,15 N) in model ClH:NH3 complexes [55], and a hydrogen-bonded ClH:pyridine complex [56]. Generally, a correlation between the 2h J( 15 N, X) coupling constants and the distance between the 15 N and X nuclei was observed.…”

Section: Tl)mentioning

confidence: 99%

15N NMR Spectroscopy in Structural Analysis: An Update (2001 - 2005)

Marek¹,

Lyčka²,

Kolehmainen³

et al. 2007

COC

133

110

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Since our previous review article (Curr. Org. Chem. 2002, 6, 35), significant improvements and an array of 15 N NMR applications in structural analysis have been published. This report aims to update coverage of improvements in methodology and various types of applications published over the period 2001 -2005. Substantial progress in cryogenic probe technology and the commercial availability of cryoprobes have facilitated the measurement of 15 N NMR parameters.The number of solid-state applications has increased significantly during the past few years. In contrast to our previous review, this article covers 15 N solid-state studies. The 15 N NMR chemical shifts of organic molecules are routinely measured by using cross-polarization magic-angle spinning (CP/MAS) techniques. The principal values of the chemical shift tensors can also be determined. 1 H-15 N and 2 H-15 N distance measurements made by means of 1 H detection are currently used in NMR crystallography.User friendly quantum chemical programs allow for the routine calculation of 15 N chemical shielding and indirect spinspin coupling constants, especially using density functional theory (DFT).Applications of 15 N NMR spectroscopy in various fields of chemistry are summarized here. Major sections represent tautomerism, complexation, protonation, and hydrogen bonding. The other topics comprise N-alkylation, N-oxidation, regioisomerism, and changes in configuration or conformation.

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“…Enaminones, due to their ability to react with both electrophiles and nucleophiles, are versatile synthons, and not only in heterocyclic chemistry (for many reviews see, e.g., [2–6]). During the past several years we have dealt with the reaction of various enaminones with diazonium salts and established a number of methods for the construction of some important or unusual heterocyclic systems [7–15], including a simple protocol leading from enaminones 1 to 6-substituted 4-amino-5-aryldiazenyl-1-arylpyridazinium salts 2 [14–15]. The procedure consists of the reaction of the corresponding enaminones and two equivalents of diazonium tetrafluoroborates or hexafluorophosphates with the later giving better yields and applicability (Scheme 1, top).…”

Section: Introductionmentioning

confidence: 99%

“…Our method does not require any additive, and the transformation from 1 to 2 is performed as a one-pot procedure. Different substrates are used and different and novel pyridazinium patterns are built under mild conditions [14–15]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

Josefík¹,

Svobodová²,

Bertolasi³

et al. 2013

Beilstein J. Org. Chem.

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SummaryEasily obtainable cyclic enaminones (piperidin-2-ylidenealkanones) can be transformed into substituted bicyclic pyridazinium tetrafluoroborates upon treatment with corresponding diazonium salts. The transformation can be performed either in a one-pot way or in a two-step process with the isolation of single azo-coupled enaminone as the intermediate. The former method is superior. Under the optimized conditions, a number of pyridazinium salts substituted with both electron-donating and electron-withdrawing substituents was easily synthesized. A mechanism of the formation of the pyridazinium salts is suggested. A partial drawback is the possibility of the formation of a mixture of products when using a different diazonium salt in each step due to a reversibility of the azo coupling. This can be suppressed by using a more reactive diazonium salt before a less reactive one.

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Formation of Pyridazinium Salts by Azo Coupling of N‐Substituted 3‐Amino‐1‐phenylbut‐2‐en‐1‐ones and Diazonium Salts

Cited by 15 publications

References 31 publications

The cyanobacterial metabolite nocuolin a is a natural oxadiazine that triggers apoptosis in human cancer cells

The cyanobacterial metabolite nocuolin a is a natural oxadiazine that triggers apoptosis in human cancer cells

15N NMR Spectroscopy in Structural Analysis: An Update (2001 - 2005)

A simple, enaminone-based approach to some bicyclic pyridazinium tetrafluoroborates

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