Yıl: 2021 Cilt: 45 Sayı: 6 Sayfa Aralığı: 1980 - 1987 Metin Dili: İngilizce DOI: 10.3906/kim-2105-59 İndeks Tarihi: 01-07-2022

A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines

Öz:
A novel four component modified Biginelli reaction for the synthesis of C-2 functionalized dihydropyrimidines has been established. The approach uses assembly of less explored acetyl acetone with aromatic aldehyde, thiourea, and dimethyl sulphate to construct a novel 5-acetyl 2-methylthio dihydropyrimidine system, which works as an efficient well-designed intermediate for generating C-2 modified Biginelli libraries with nitrogen nucleophiles. Phenyl hydrazine, semicarbazide, and aryl semicarbazides are successfully used as N-nucleophiles to generate C-2 functionalized dihydropyrimidine derivatives, which fulfil the demands of active pharmacophore. Time economy, step economy, and a single pot reaction with moderate to excellent yield are the major advantages of this novel method.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Zarganes-Tzitzikas T, Dömling A. Modern multicomponent reactions for better drug syntheses. Organic Chemistry Frontiers 2014; 1: 834–837. doi: 10.1039/c4qo00088a
  • 2. Herrera RP, Marqués-López E. Multicomponent Reactions: Concepts and Applications for Design and Synthesis. First edition, John Wiley & Sons, Inc, Hoboken, NJ, 2015. doi: 10.1002/9781118863992
  • 3. Slobbe P, Ruijter E, Orru RVA. Recent applications of multicomponent reactions in medicinal chemistry. Medicinal Chemistry Communications 2012; 3: 1189–1218. doi: 10.1039/c2md20089a
  • 4. John SE, Gulati S, Shankaraiah N. Recent advances in multi-component reactions and their mechanistic insights : a triennium review. Organic Chemistry Frontiers 2021; 8: 4237–4287. doi: 10.1039/d0qo01480j
  • 5. Biginelli P. Aldehyde-Urea Derivatives of Aceto- and Oxaloacetic Acids. A Gazzetta chimica italiana 1893; 23: 360–413.
  • 6. Kappe CO, Stadler A. The Biginelli Dihydropyrimidine Synthesis. In: Larry Overman (Editors). Organic Reactions. John Wiley & Sons, 2004. doi: 10.1002/0471264180.or063.01
  • 7. Heravi MM, Zadsirjan V. Recent Advances in Biginelli-type Reactions, Current Organic Chemistry 2020; 24: 1331–1366. doi: 10.2174/13 85272824999200616111228
  • 8. Nagarajaiah H, Mukhopadhyay A, Moorthy JN. Biginelli reaction: an overview. Tetrahedron Letters 57 (2016) 5135–5149. doi: 10.1016/j. tetlet.2016.09.047
  • 9. Kaur R, Chaudhary S, Kumar K, Gupta MK, Rawal RK. Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review. European Journal of Medicinal Chemistry 2017; 132: 108–134. doi: 10.1016/j.ejmech.2017.03.025
  • 10. Fátima  de, Braga TC, Neto L da S, Terra BS, Oliveira BGF et al. A mini-review on Biginelli adducts with notable pharmacological properties. Journal of Advanced Research 2015; 6: 363–373. doi: 10.1016/j.jare.2014.10.006
  • 11. Matos L, Masson F, Simeoni L, Homem-de-mello M. Biological activity of dihydropyrimidinone (DHPM) derivatives: A systematic review. European Journal of Medicinal Chemistry 2018; 143: 1779–1789. doi: 10.1016/j.ejmech.2017.10.073
  • 12. Malik M, Seddigi Z, Bajee S, Azeeza S, Riyaz S et al. Multicomponent access to novel proline / cyclized cysteine tethered monastrol conjugates as potential anticancer agents. Journal of Saudi Chemical Society 2019; 23: 503–513. doi: 10.1016/j.jscs.2019.01.003
  • 13. Gasperi T, Orsini M, Vetica F, Figueiredo R. Organocatalytic asymmetric multicomponent reactions. In: Multicomponent Reactions: Concepts and Applications for Design and Synthesis. First edition, John Wiley & Sons, 2015.
  • 14. Zhu J, Wang Q. Multicomponent Reactions in Organic Synthesis. First Edition, Wiley-VCH Verlag GmbH & Co. KGaA., 2015. doi: 10.1002/9783527678174.ch10
  • 15. Graebin C, Ribeiro F, Rogério K, Kümmerle A. Multicomponent Reactions for the Synthesis of Bioactive Compounds: A Review. Current Organic Synthesis 2019; 16: 855–899. doi: 10.2174/1570179416666190718153703
  • 16. Singh K, Singh K. Biginelli Condensation: Synthesis and Structure Diversification of 3,4-Dihydropyrimidin-2(1H)-one Derivatives, içinde: Advances in Heterocyclic Chemistry, Elsevier Inc., 2012: 223–308. doi: 10.1016/B978-0-12-396530-1.00003-6
  • 17. Narkhede H, Nevagi R, Kumbhare M, Kaur P. Synthesis and in-vitro screening of novel dihydropyrimidine derivatives as potential calcium channel blockers. Der Pharma Chemica 2014; 6: 221–227.
  • 18. Nevagi R, Narkhede H. Novel dihydropyrimidine derivatives as antibacterial agents. Der Pharma Chemica 2014; 6: 135–139.
  • 19. Mostafa A, Selim K. Synthesis and anticancer activity of new dihydropyrimidinone derivatives. European Journal of Medicinal Chemistry 2018; 156: 304–315. doi: 10.1016/j.ejmech.2018.07.004
  • 20. Li Y, Tan T, Zhao Y, Wei Y, Wang D et al. Anticancer polymers via the Biginelli reaction. ACS Macro Letters 2020; 9 : 1249–1254. doi: 10.1021/acsmacrolett.0c00496
  • 21. Huseynzada A, Jelch C, Akhundzada H, Soudani S, Ben C et al. Synthesis, crystal structure and antibacterial studies of dihydropyrimidines and their regioselectively oxidized products. RSC Advances 2021; 11: 6312–6329. doi: 10.1039/D0RA10255E
  • 22. Sawant R, Sarode V. Synthesis, spectral characterization and analgesic activity of 2-methylthio-1,4-dihydropyrimidines. Iranian Journal of Pharmaceutical Research 2011; 10: 733–739. doi: 10.22037/ijpr.2011.1022
  • 23. Singh B, Mishra M, Saxena N, Yadav G, Maulik P. Synthesis of 2-sulfanyl-6-methyl-1 , 4-dihydropyrimidines as a new class of antifilarial agents. European Journal of Medicinal Chemistry 2008; 43: 2717–2723. doi: 10.1016/j.ejmech.2008.01.038
  • 24. Kaur H, Machado M, Kock C, Smith P, Chibale K. Primaquine-pyrimidine hybrids: Synthesis and dual-stage antiplasmodial activity. European Journal of Medicinal Chemistry 2015; 101: 266–273. doi: 10.1016/j.ejmech.2015.06.045
  • 25. Atwal K, Rovnyak G, Schwartz J, Moreland S, Hedberg A et al. Dihydropyrimidine calcium channel blockers: 2-Heterosubstituted 4-Aryl1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines. Journal of Medicinal Chemistry 1990; 33: 1510–1515.
  • 26. Singh K, Singh K, Wan B, Franzblau S, Chibale K. Facile transformation of Biginelli pyrimidin-2(1H)-ones to pyrimidines. In vitro evaluation as inhibitors of Mycobacterium tuberculosis and modulators of cytostatic activity. European Journal of Medicinal Chemistry 2011; 46: 2290–2294. doi: 10.1016/j.ejmech.2011.03.010
  • 27. Shildneck W. Organic Synthesis, Collective Volume -II, John Wiley & Sons, 1943.
  • 28. Li JJ. Biginelli reaction. In: Name Reactions. Springer International Publishing, Cham, 2021. doi: 10.1007/978-3-030-50865-4
  • 29. Merck Index, An Encyclopedia of Chemicals, drugs and biologicals. (2006) 5956.
  • 30. Dallinger D, Kappe C. Creating chemical diversity space by scaffold decoration of dihydropyrimidines. Pure and Applied Chemistry 2005; 77: 155–161. doi: 10.1351/pac200577010155
APA NARKHEDE H, DHAKE A, Vaidhyanathan B (2021). A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. , 1980 - 1987. 10.3906/kim-2105-59
Chicago NARKHEDE HARSHA,DHAKE AVINASH,Vaidhyanathan Balasubramaniyan A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. (2021): 1980 - 1987. 10.3906/kim-2105-59
MLA NARKHEDE HARSHA,DHAKE AVINASH,Vaidhyanathan Balasubramaniyan A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. , 2021, ss.1980 - 1987. 10.3906/kim-2105-59
AMA NARKHEDE H,DHAKE A,Vaidhyanathan B A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. . 2021; 1980 - 1987. 10.3906/kim-2105-59
Vancouver NARKHEDE H,DHAKE A,Vaidhyanathan B A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. . 2021; 1980 - 1987. 10.3906/kim-2105-59
IEEE NARKHEDE H,DHAKE A,Vaidhyanathan B "A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines." , ss.1980 - 1987, 2021. 10.3906/kim-2105-59
ISNAD NARKHEDE, HARSHA vd. "A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines". (2021), 1980-1987. https://doi.org/10.3906/kim-2105-59
APA NARKHEDE H, DHAKE A, Vaidhyanathan B (2021). A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. Turkish Journal of Chemistry, 45(6), 1980 - 1987. 10.3906/kim-2105-59
Chicago NARKHEDE HARSHA,DHAKE AVINASH,Vaidhyanathan Balasubramaniyan A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. Turkish Journal of Chemistry 45, no.6 (2021): 1980 - 1987. 10.3906/kim-2105-59
MLA NARKHEDE HARSHA,DHAKE AVINASH,Vaidhyanathan Balasubramaniyan A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. Turkish Journal of Chemistry, vol.45, no.6, 2021, ss.1980 - 1987. 10.3906/kim-2105-59
AMA NARKHEDE H,DHAKE A,Vaidhyanathan B A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. Turkish Journal of Chemistry. 2021; 45(6): 1980 - 1987. 10.3906/kim-2105-59
Vancouver NARKHEDE H,DHAKE A,Vaidhyanathan B A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines. Turkish Journal of Chemistry. 2021; 45(6): 1980 - 1987. 10.3906/kim-2105-59
IEEE NARKHEDE H,DHAKE A,Vaidhyanathan B "A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines." Turkish Journal of Chemistry, 45, ss.1980 - 1987, 2021. 10.3906/kim-2105-59
ISNAD NARKHEDE, HARSHA vd. "A four-component modified Biginelli reaction: A novel approach for C-2 functionalized dihydropyrimidines". Turkish Journal of Chemistry 45/6 (2021), 1980-1987. https://doi.org/10.3906/kim-2105-59