Molecular Diversity

, Volume 15, Issue 1, pp 263–267 | Cite as

Diversity-oriented, one-pot, multi-component synthesis of substituted uracil derivatives

  • Yogesh Y. Pedgaonkar
  • Mariam S. Degani
  • Radhakrishnan P. Iyer
Short Communication


With the emergence of high throughput screening of bioactive molecules, there is constant need for the development of new strategies for diversity-oriented synthesis. We describe here a novel one-pot multicomponent reaction for the synthesis of uracil derivatives using easily available starting materials. This new synthetic strategy provides easy access to diverse uracil derivatives in moderate to good yields.

Graphical Abstract


Multicomponent reaction Carbonylation Cyclization 5-cyanouracil Triphosgene MCR 


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Supplementary material

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  1. 1.
    Loksha YM, Pedersen EB, Loddo R, La Colla Paolo (2009) Synthesis and anti-HIV-1 activity of 1-substiuted 6-(3-cyanobenzoyl) and [(3-cyanophenyl)fluoromethyl]-5-ethyluracils. Archiv der Pharmazie 342: 501–506. doi: 10.1002/ardp.200900058 PubMedCrossRefGoogle Scholar
  2. 2.
    Safonova TS, Nemeryuk MP, Likhovidova MM, Grineva NA, Keremov AF, Solov’eva NP, Anisimova OS (2008) Synthesis, properties, and reactions of derivatives of 1,3-dimethyl-6-(5’-aminopyrimidylthio-6’)uracils. Pharm Chem J 42: 11–14. doi: 10.1007/s11094-008-0046-5 CrossRefGoogle Scholar
  3. 3.
    Maruyama T, Kozai S, Demizu Y, Witvrouw M, Pannecouque C, Balzarini J, Snoecks R, Andrei G, De Clercq E (2006) Synthesis and anti-HIV-1 and anti-HCMV activity of 1-substituted 3-(3,5-dimethylbenzyl)uracil derivatives. Chem Pharm Bull 54: 325–333. doi: 10.1248/cpb.54.325 PubMedCrossRefGoogle Scholar
  4. 4.
    Prachayasittikul S, Sornsongkhram N, Pingaew R, Worachartcheewan A, Ruchirawat S, Prachayasittikul V (2009) Synthesis of N-substituted 5-iodouracils as antimicrobial and anticancer agents. Molecules 14: 2768–2779. doi: 10.3390/molecules14082768 PubMedCrossRefGoogle Scholar
  5. 5.
    Núñez CM, Pavani GM, Díaz-Gavilán M, Rodríguez-Serrano F, Gómez-Vidal AJ, Marchal AJ, Aránega A, Gallo AM, Espinosa A, Campos MJ (2006) Synthesis and anticancer activity studies of novel 1-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)uracil and (6’-substituted)-7- or 9-(2,3-dihydro-5H-1,4-benzodioxepin-3-yl)-7H- or 9H-purines. Tetrahedron 62: 11724–11733. doi: 10.1016/j.tet.2006.09.039 CrossRefGoogle Scholar
  6. 6.
    Semenov VE, Voloshina AD, Toroptzova EM, Kulik NV, Zobov VV, Giniyatullin RK, Mikhailov AS, Nikolaev AE, Akamsin VD, Reznik VS (2006) Antibacterial and antifungal activity of acyclic and macrocyclic uracil derivatives with quaternized nitrogen atoms in spacers. Eur J Med Chem 41: 1093–1101. doi: 10.1016/j.ejmech.2006.03.030 PubMedCrossRefGoogle Scholar
  7. 7.
    Zhi C, Long Z, Gambino J, Xu W, Brown CN, Barnes M, Butler M, LaMarr W, Wright EG (2003) Synthesis of substituted 6-anilinouracils and their inhibition of DNA polymerase IIIC and gram-positive bacterial growth. J Med Chem 46: 2731–2739. doi: 10.1021/jm020591z PubMedCrossRefGoogle Scholar
  8. 8.
    Yagi K, Akimoto K, Mimori N, Miyake T, Kudo M, Arai K, Ishii S (2000) Synthesis and insecticidal/acaricidal activity of novel 3-(2,4,6-trisubstituted phenyl)uracil derivatives. Pest Manag Sci 56: 65–73. doi: 10.1002/(SICI)1526-4998(200001)56:1<65::AID-PS90>3.0.CO;2-S CrossRefGoogle Scholar
  9. 9.
    Herdewijn P (2000) Heterocyclic modifications of oligonucleotides and antisense technology. Antisense Nucleic Acid Drug Dev 10: 297–310. doi: 10.1089/108729000421475 PubMedCrossRefGoogle Scholar
  10. 10.
    Kurreck J (2003) Antisense technologies: improvement through novel chemical modifications. Eur J Biochem 270: 1628–1644. doi: 10.1046/j.1432-1033.2003.03555.x PubMedCrossRefGoogle Scholar
  11. 11.
    Iyer RP, Roland A, Zhou W, Ghosh K (1999) Modified oligonucleotides—syntheses, properties, and applications. Curr Opin Mol Ther 1: 344–358Google Scholar
  12. 12.
    Chiu Yl, Rana Tm (2003) siRNA function in RNAi: a chemical modification analysis. RNA 9: 1034–1048. doi: 10.1261/rna.5103703 PubMedCrossRefGoogle Scholar
  13. 13.
    Fustero S, Piera J, Sanz-Cervera FJ, Catalán S, Ramírezde Arellano C (2004) A versatile synthesis of fluorinated uracils in solution and on solid-phase. Org Lett 6: 1417–1420. doi: 10.1021/ol049668z PubMedCrossRefGoogle Scholar
  14. 14.
    Nieto MR, Coelho A, Martínez A, Stefanachi A, Sotelo E, Raviña E (2003) Synthesis of 1-substituted-6-methyluracils. Chem Pharm Bull 51: 1025–1028. doi: 10.1248/cpb.51.1025 PubMedCrossRefGoogle Scholar
  15. 15.
    Gabel N, Binkley S (1958) Synthesis of 1-aryluracils. J Org Chem 23: 643–645. doi: 10.1021/jo01098a629 CrossRefGoogle Scholar
  16. 16.
    Senda S, Hirota K, Notani J (1972) Pyrimidine and related compounds. XVI. Synthesis of 1,3-disubstituted 5-cyanouracil derivatives and related compounds. Chem Pharm Bull 20: 1380–1388Google Scholar
  17. 17.
    Snyder RH, Jones ER (1946) Synthesis of 4-hydroxyquinolines. III. A direct synthesis of β-substituted acrylic esters. J Am Chem Soc 68: 1253–1255. doi: 10.1021/ja01211a034 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Yogesh Y. Pedgaonkar
    • 1
  • Mariam S. Degani
    • 1
  • Radhakrishnan P. Iyer
    • 2
  1. 1.Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia
  2. 2.Spring Bank Pharmaceuticals, Inc.MilfordUSA

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