Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

Krstulović, Luka; Ismaili, Hamit; Bajić, Miroslav; Višnjevac, Aleksandar; Glavaš‐Obrovac, Ljubica; Žinić, Biserka

doi:10.5562/cca2198

Cited by 9 publications

(4 citation statements)

References 17 publications

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“…Preparation of N-Alkyl N-Sulfonylamidino Thymine Derivatives N-1 substituted thymine 1 [10] was reacted with tetrabutylammonium fluoride (TBAF) in dry THF producing new N-3 substituted thymine 5 and N-1, N-3-disubstituted thymine 4 along with unreacted starting compound 1. Additionally, acryl sulfonamidine 3 and free thymine 2 were also identified, confirming that the reaction proceeds through the retro-Michael/Michael addition reaction sequence.…”

Section: Methodsmentioning

confidence: 99%

“…The amidine group is present in many compounds capable of interacting with a wide range of biological targets [5], resulting in anti-degenerative [6], anticancer [7,8] and antimicrobial activities [9]. These findings encouraged us to explore the synthesis and chemistry of novel N-sulfonylamidino derivatives containing pyrimidine moiety II ( Figure 1) and to study their biological properties [10].…”

Section: Introductionmentioning

confidence: 99%

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Mass Spectrometry and Theoretical Studies on N–C Bond Cleavages in the N-Sulfonylamidino Thymine Derivatives

Kobetić

Kazazić

Kovačević

et al. 2015

J. Am. Soc. Mass Spectrom.

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The reactivity of new biologically active thymine derivatives substituted with 2-(arylsulfonamidino)ethyl group at N1 and N3 position was investigated in the gas phase using CID experiments (ESI-MS/MS) and by density functional theory (DFT) calculations. Both derivatives show similar chemistry in the negative mode with a retro-Michael addition (Path A(-)) being the most abundant reaction channel, which correlate well with the fluoride induced retro-Michael addition observed in solution. The difference in the fragmentation of N-3 substituted thymine 5 and N-1 substituted thymine 1 in the positive mode relates to the preferred cleavage of the sulfonyl group (m/z 155, Path B) in N-3 isomer and the formation of the acryl sulfonamidine 3 (m/z 309) via Path A in N-1 isomer. Mechanistic studies of the cleavage reaction conducted by DFT calculations give the trend of the calculated activation energies that agree well with the experimental observations. A mechanism of the retro-Michael reaction was interpreted as a McLafferty type of fragmentation, which includes Hβ proton shift to one of the neighboring oxygen atoms in a 1,5-fashion inducing N1(N3)-Cα bond scission. This mechanism was found to be kinetically favorable over other tested mechanisms. Significant difference in the observed fragmentation pattern of N-1 and N-3 isomers proves the ESI-MS/MS technique as an excellent method for tracking the fate of similar sulfonamidine drugs. Also, the observed N-1 and/or N-3 thymine alkylation with in situ formed reactive acryl sulfonamidine 3 as a Michael acceptor may open interesting possibilities for the preparation of other N-3 substituted pyrimidines.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mass Spectrometry and Theoretical Studies on N–C Bond Cleavages in the N-Sulfonylamidino Thymine Derivatives

Kobetić

Kazazić

Kovačević

et al. 2015

J. Am. Soc. Mass Spectrom.

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“…[19] published the synthesis of tosylacrylimidamide, and in 2016 Rashinkar et. al [20][21] have successfully reported the synthesis and anticancer activity against breast cancer cell lines of tosylacrylimidamide derivatives. So, based on the docking studies of the said compounds we have decided to explore the anti-diabetic activity of the same compound on MIN-6 cell lines.…”

Section: Introductionmentioning

confidence: 99%

Scrutiny of Novel Tosylacrylimidamide as Non‐Classical Bioisosteres of Sulfonylurea in Type II Diabetes Mellitus through Synthesis, In Vitro and Docking Studies

Surve

Gurav

et al. 2022

ChemistrySelect

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Sulfonylureas is being used throughout the world for the treatment of diabetes mellitus. The aim of the present study was to investigate mode of action of tosylacrylimidamide. Tosylacrylimidamide a non-classical bioisosteres of sulfonyl urea, bioisosteres refer to structurally distinct molecules eliciting a similar biological effect. In the present study we have determined the ability of tosylacrylimidamide to stimulate insulin secretion from MIN-6 cells. The compounds were tested in the presence of 5 mM glucose concentration, our results indicates that compound 4 e, 4 f, 4 g were the most effective insulin secretagogue's amongst reported, then 4 e, 4 f, 4 g were further evaluated at various concentration of compound keeping glucose concentration constant (5 mM), resulting 4 e showed 4.34 fold increase in insulin secretion at 1 mg/ml of compound, 4 f showed 7.4 fold increase in insulin secretion at 5 mg/ml of compound and 4 g has shown 7.6 fold increase in insulin secretion at 5 mg/ml of compound. The rest of the tosylacrylimidamide in our assay had only marginal effects on insulin secretion[a] S.

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“…A variety of methods have been developed for the synthesis of N-sulfonyl amidines. The most commonly used methods to prepare these compounds include the Cu-catalyzed multicomponent reaction of alkynes, sulfonyl azides and amines [23][24][25][26][27][28][29][30][31], the reaction of thioacetamide derivatives and cyclic thioamides with sulfonyl azides [22,32,33], the chlorophosphite-mediated Beckmann reaction of oximes with p-toluenesulfonyl azide [34], the sulfonyl ynamide rearrangement by treatment with amines [35], the sodium iodide catalyzed reaction of sulfonamide with formamide [36], and the condensation of sulfonamide derivatives with DMF-DMA [37].…”

Section: Introductionmentioning

confidence: 99%

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

Ilkin¹,

Berseneva²,

Beryozkina³

et al. 2020

Beilstein J. Org. Chem.

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N-Sulfonyl amidines bearing 1,2,3-triazole, isoxazole, thiazole and pyridine substituents were successfully prepared for the first time by reactions of primary, secondary and tertiary heterocyclic thioamides with alkyl- and arylsulfonyl azides. For each type of thioamides a reliable procedure to prepare N-sulfonyl amidines in good yields was found. Reactions of 1-aryl-1,2,3-triazole-4-carbothioamides with azides were shown to be accompanied with a Dimroth rearrangement to form 1-unsubstituted 5-arylamino-1,2,3-triazole-4-N-sulfonylcarbimidamides. 2,5-Dithiocarbamoylpyridine reacts with sulfonyl azides to form a pyridine bearing two sulfonyl amidine groups.

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Synthesis of Novel Aliphatic N-sulfonylamidino Thymine Derivatives by Cu(I)-catalyzed Three-component Coupling Reaction

Cited by 9 publications

References 17 publications

Mass Spectrometry and Theoretical Studies on N–C Bond Cleavages in the N-Sulfonylamidino Thymine Derivatives

Mass Spectrometry and Theoretical Studies on N–C Bond Cleavages in the N-Sulfonylamidino Thymine Derivatives

Scrutiny of Novel Tosylacrylimidamide as Non‐Classical Bioisosteres of Sulfonylurea in Type II Diabetes Mellitus through Synthesis, In Vitro and Docking Studies

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

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