Amebicides. I. Some 1-(1,4-Dihydro-1,4-dioxo-3-hydroxy-2-naphthyl)-pyridinium Betaines

Truitt, Price; Mahon, Frank; Platas, Oscar R.; Hall, Richard; Eris, Talib El

doi:10.1021/jo01076a026

Cited by 7 publications

(4 citation statements)

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“…Although much work has been concentrated upon the search for novel prodrug derivatives of modified pyrimidine nucleobases 5 including 5-fluorouracil (5-FU), widely used as an antitumor agent, not much interest has been developed in the synthesis of new highly dipolar pyrimidines as potential biologically active compounds. However, the activities of known positively charged and betainic heterocyclic systems that are hetarenium-substituted cover the range from antitrichomonal, antileishmanial, amebicidal, and antiprotozoal agents, acetylcholin-esterase reactivators, and herbicides to semiconductors . Furthermore, the chemistry and widespread use of uracils as active principles have recently been reviewed …”

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confidence: 99%

Charged and Betainic Nucleobases. On Syntheses and Properties of First Mesomeric Uracilylbetaines, Uracilates, and Novel Uracilium Salts

Schmidt

Kindermann

1997

J. Org. Chem.

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Nucleophilic heteroaromatic substitution of DMAP and 1-methylimidazole on the 6-chlorouracil 1 gave the uracilyl hetarenium salts 2 and 4, respectively. Depending on the nucleophile, the substitution could be catalyzed by interception of the leaving group either with sodium tetraphenylborate or with antimony pentachloride in a non-coordinating solvent. Catalysis with other Lewis acids failed due to the formation of stable coordination compounds 3. Surprisingly, Finkelsteintype reaction conditions provide an efficient approach to the imidazolium iodide 4. Depending on the reaction conditions, treatment of the 6-chlorouracil 5 with DMAP resulted in the formation of the pyridinium uracilate 6, the uracilyl pyridinium chloride 7a, and the novel pyridinium-uracilate 8 which is a cross-conjugated mesomeric betaine (CCMB). Alkylation of the mesomeric betaine 8 with 1,2-dichloroethane/SbCl 5 gave the biscation 9. Analogously, 1-methylimidazole or 2,4,6trimethylpyridine as nucleophiles formed the salts 10a and 12, respectively, and the imidazoliumuracilate 11. This is the first representative of a cross-conjugated heterocyclic mesomeric betaine isoconjugate with odd nonalternant hydrocarbon anions. PM3 calculations were performed on the cation 2 and on the mesomeric betaine 8. Whereas the cation 2 was found to have an essentially perpendicular torsional angle Φ around the CN + bond linking the uracil and the pyridinium units, the mesomeric betaine 8 adopts a nearly planar conformation, thus allowing stabilizing π interactions. Accordingly, upon rotation about the CN + bond, the expected maxima were found at essentially perpendicular conformations. Due to the balance between three effects which act in opposite directions, (i) stabilizing p overlap, (ii) N(8)/2-H attractive interaction, and (iii) steric repulsion between 6-H and 12-H, two additional small minima were surprisingly found at Φ ) 36.6°and 219.3°. The charge separation in the ground state of the mesomeric betaine 11, and the ground-state ion-pair complexes of the hetarenium iodides 2d, 4, 7c, and 10b were confirmed by the effect of negative solvatochromism. X

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confidence: 99%

Charged and Betainic Nucleobases. On Syntheses and Properties of First Mesomeric Uracilylbetaines, Uracilates, and Novel Uracilium Salts

Schmidt

Kindermann

1997

J. Org. Chem.

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“…The importance of these compounds can be exemplified by the interesting biological activities associated with many 3-alkyl-or 3-alkylamino-substituted derivatives of 2-hydroxy-1,4-naphthoquinone or 2-chloro-1,4-naphthoquinones ( Fig. 1) [22].…”

Section: Introductionmentioning

confidence: 99%

Novel 2,3-disubstituted 1,4-naphthoquinone derivatives and their metal complexes – Synthesis and in vitro cytotoxic effect against mouse fibrosarcoma L929 cells

Niculescu¹,

Muresan

Sălăgeanu

et al. 2012

Journal of Organometallic Chemistry

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“…) [23] . Ullmann 's betaine ( 15 )[24] is comparable to 4 in that the charges are mainly located in fragments that correspond to a pyridinium cation and a 1,3‐diketonate anion, but they are connected in such a way that the negative charge is also conjugated into the pyridine unit. Three C‐atoms bear both positive and negative charges in suitable canonic resonance structures, which means that in contrast to 4 , 15 is a conjugated mesomeric betaine.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Tetraoxygenated Terephthalates via a Dichloroquinone Route: Characterization of Cross‐Conjugated Liebermann Betaine Intermediates

Hintermann¹,

Altmann²,

Naumov

et al. 2017

Helvetica Chimica Acta

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Cross‐conjugated quinoid betaines 4 (2,5‐bis(alkoxycarbonyl)‐3,6‐dioxo‐4‐(1‐pyridinium‐1‐yl)cyclohexa‐1,4‐dien‐1‐olates; Liebermann betaines) were synthesized from 2,5‐dichloro‐3,6‐dioxocyclohexa‐1,4‐diene‐1,4‐dicarboxylates (2) and pyridines in acetone containing H2O. Their structure was secured by NMR spectroscopy and by X‐ray diffraction analysis of 4f (alkoxy = EtO, pyridine = 4‐Me2N–C5H4N). Betaines 4 show comparatively high reactivity towards nucleophiles as a consequence of their cross‐conjugated character. Betaine 4a and hydroxy‐3,4‐methylenedioxybenzene (sesamol) condense to give a pyridinium quinolate salt 14 which has a bifurcate H‐bond from a pyridinium N+–H donor to both carbonyl (C=O) and olate (C–O−) acceptors in the solid state. Betaine 4b hydrolyzes in aqueous solution to give diethyl 2,5‐dihydroxy‐3,6‐dioxocyclohexa‐1,4‐diene‐1,4‐dicarboxylate (11) as a pyridinium salt, or as polymeric zinc(II) complex of the dianion of 11 in the presence of ZnCl2. Dihydroxyquinone 11 was analytically differentiated from its independently prepared hydroquinone form, diethyl 2,3,5,6‐tetrahydroxyterephthalate (12), by NMR analysis in solution and X‐ray crystal structure determination of both compounds.

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Amebicides. I. Some 1-(1,4-Dihydro-1,4-dioxo-3-hydroxy-2-naphthyl)-pyridinium Betaines

Cited by 7 publications

References 0 publications

Charged and Betainic Nucleobases. On Syntheses and Properties of First Mesomeric Uracilylbetaines, Uracilates, and Novel Uracilium Salts

Charged and Betainic Nucleobases. On Syntheses and Properties of First Mesomeric Uracilylbetaines, Uracilates, and Novel Uracilium Salts

Novel 2,3-disubstituted 1,4-naphthoquinone derivatives and their metal complexes – Synthesis and in vitro cytotoxic effect against mouse fibrosarcoma L929 cells

Synthesis of Tetraoxygenated Terephthalates via a Dichloroquinone Route: Characterization of Cross‐Conjugated Liebermann Betaine Intermediates

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