Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones and related compounds

Sośnicki, Jacek G.; Idzik, Tomasz J.; Borzyszkowska, Aleksandra; Wróblewski, Emil; Maciejewska, Gabriela; Struk, Łukasz

doi:10.1016/j.tet.2016.12.024

Cited by 12 publications

(25 citation statements)

References 45 publications

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“…Finally, both NH and N-substituted 3,4-dihydropyridin-2-ones were transformed to their sulphur analogues S1 - 4 and S8 - 22 by thionation using Lawesson’s reagent. Compounds S5 was obtained by addition of benzylmagnesiate to 2-thiopyridone as described earlier [ 15 ], while compound S7 was achieved by thionation of oxygen analogue O7 , obtained by addition of benzylmagnesiate to N-Me 5-phenylpyridin-2-one. Product S6 was gained by thionation of oxygen analogue O6 , obtained as by-product during benzylation conducted with bigger amount of MeLi in comparison to a standard procedure.…”

Section: Resultsmentioning

confidence: 99%

“…Grignard reagent A was obtained in 64% yield (0.13 M), B 29 % yield (0,06 M). (4 RS )-4-Benzyl-5-phenyl-3,4-dihydropyridin-2(1 H )-one ( O1 ) [ 15 ] Yield 62%. Spectra of compound O1 are in agreement with literature data [ 15 ].…”

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

“…(4 RS )-4-Benzyl-5-phenyl-3,4-dihydropyridin-2(1 H )-one ( O1 ) [ 15 ] Yield 62%. Spectra of compound O1 are in agreement with literature data [ 15 ]. Note: In the step of lithation of 2-pyridone 1.7-fold excess was used and in this conditions apart from O1 also by-product O6 was obtained.…”

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

“…1,4-Dibenzyl-5-phenyl-3,4-dihydropyridin-2(1 H )-one [ 15 ]( O4 ): Prepared according to the procedure described earlier [ 15 ]. 6-Benzyl-1-methyl-5-phenyl-3,6-dihydropyridin-2(1 H )-one ( O7 ): Prepared according to the procedure described earlier [ 15 ]. The crude product purified by column chromatography (SiO 2 , n -hexane: ethyl acetate 3:1), gave light cream semisolid in 82 % yield.…”

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

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Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Perużyńska

Borzyszkowska-Ledwig

Sośnicki

et al. 2021

IJMS

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Most anticancer drugs target mitosis as the most crucial and fragile period of rapidly dividing cancer cells. However the limitations of classical chemotherapeutics drive the search for new more effective and selective compounds. For this purpose structural modifications of the previously characterized pyridine aalog (S1) were incorporated aiming to obtain an antimitotic inhibitor of satisfactory and specific anticancer activity. Structure-activity relationship analysis of the compounds against a panel of cancer cell lines allowed to select a compound with a thiophene ring at C5 of a 3,4-dihydropyridine-2(1H)-thione (S22) with promising antiproliferative activity (IC50 equal 1.71 ± 0.58 µM) and selectivity (SI = 21.09) against melanoma A375 cells. Moreover, all three of the most active compounds from the antiproliferative study, namely S1, S19 and S22 showed better selectivity against A375 cells than reference drug, suggesting their possible lower toxicity and wider therapeutic index. As further study revealed, selected compounds inhibited tubulin polymerization via colchicine binding site in dose dependent manner, leading to aberrant mitotic spindle formation, cell cycle arrest and apoptosis. Summarizing, the current study showed that among obtained mitotic-specific inhibitors analogue with thiophene ring showed the highest antiproliferative activity and selectivity against cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

Section: Appendix A1 Synthesis Of Precursors Of Compounds mentioning

confidence: 99%

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Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Perużyńska

Borzyszkowska-Ledwig

Sośnicki

et al. 2021

IJMS

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“…In 2018 Sośnicki and co-workers synthesized bromofunctionalized 2,6-methanobenzomorphanones 228 132 starting from the addition of benzylmagnesate 226 to Nsubstituted 2-pyridones P-110, which, in contrast to the above described addition of a Grignard reagent (Scheme 82), delivered mainly 6-benzyl-3,6-dihydro-2-pyridones 227 (Scheme 83). 133 These were cyclized to give 11-bromobenzomorphanones 228 using NBS in nitromethane in the presence of triphenyl phosphite. The introduced bromine atom enabled further transformation to novel cyclopropane-fused benzomorphanones 229 (Scheme 83).…”

Section: J G Sośnicki T J Idzikmentioning

confidence: 99%

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Sośnicki¹,

Idzik²

2019

Synthesis

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2-Pyridone is characterized by a very wide range of reactivity of a different nature, ranging from electrophilic aromatic substitution, CH–metal-mediated reactions, and NH/OH functionalization of both possible lactam/lactim tautomers, through cycloaddition, to nucleophilic addition and transformation of the tautomeric C=O/C–OH moiety. The high availability of 2-pyridones and the possibility of their far-reaching functionalization additionally increased their values. Therefore, they are very useful building blocks for the synthesis of structurally diverse piperidine and pyridine compounds, including naturally occurring 2-pyridones. This review reports on the use of simple 2-pyridones in the synthesis of alkaloids and alkaloids-inspired compounds based on the piperidine or pyridine framework.1 Introduction2 Structure, Availability, and Reactivity of 2-Pyridones3 Monocyclic Piperidine Alkaloids from 2-Pyridones4 Polycyclic Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds from 2-Pyridones4.1 New Ring Formation Involving C/N Atoms of the 2-Pyridone Ring4.1.1 Indolizine-Fused 2-Pyridones: Camptothecins and Related Compounds4.1.2 Other Indolizines from 2-Pyridones4.1.3 Compounds Bearing the Quinolizine Ring System4.2 New Ring Formation Involving C/C Atoms of the 2-Pyridone Ring4.2.1 C-2/C-3 Ring Fusion4.2.2 C-3/C-4 Ring Fusion4.2.3 C-4/C-5 Ring Fusion4.2.4 C-5/C-6 Ring Fusion4.2.5 C-2/C-4 Ring Bridge4.2.6 C-2/C-6 Ring Bridge4.2.7 C-3/C-5 Ring Bridge4.2.8 C-3/C-6 Ring Bridge4.2.9 C-4/C-6 Ring Bridge5 Conclusion

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Nucleophilic Aliphatic Substitution

Moloney

2020

Organic Reaction Mechanisms Series

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Addition of novel benzylmagnesium “ate” complexes of BnR2MgLi type to 2-(thio)pyridones and related compounds

Cited by 12 publications

References 45 publications

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Synthesis and Anticancer Activity of Mitotic-Specific 3,4-Dihydropyridine-2(1H)-thiones

Pyridones – Powerful Precursors for the Synthesis of Alkaloids, Their Derivatives, and Alkaloid-Inspired Compounds

Nucleophilic Aliphatic Substitution

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