Medicinal Chemistry Research

, Volume 23, Issue 3, pp 1180–1188 | Cite as

Synthesis of pyranochromene and pyranopyrimidine derivatives from substituted natural coumarin isolated from Ammi majus L. and their biological evaluation

  • N. H. Ouf
  • Y. A. SelimEmail author
  • M. I. Sakran
  • A. S. Badr El-din
Original Research


A series of novel coumarin derivatives were synthesized from 6-hydroxy-7-methoxy-4-methyl coumarin which was isolated from the aerial parts of the Egyptian medicinal plant Ammi majus L. (Apiaceae). The key intermediate 3-amino-5-methoxy-1-(4-methoxyphenyl)-10-methyl-8-oxo-1,8-dihydropyrano[3,2-f]chromene-2-carbonitrile (3c) was obtained in one-pot synthesis by treating α-cyanocinnamonitrile (1-c) with the natural compound: 6-hydroxy-7-methoxy-4-methyl coumarin (2). Chemical, elemental and spectroscopic evidences confirmed the structures of the synthesized compounds. Some of the newly synthesized compounds exhibited better anti-inflammatory activities at low concentrations compared with indomethacin as positive control.


Coumarin Pyranochromene Pyranopyrimidinochromene Anti-inflammatory 



The authors gratefully acknowledge the financial support by Greece and are thankful to the Lab. of organic chemistry (natural product synthesis), Department of Chemistry, Faculty of science Aristotle University of Thessaloniki, Thessaloniki, Greece for the assistance in the performance of some experiments of 1D&2D NMR & MS spectral analyses.


  1. Bedair AH, Nagwa AE, Abd El-Latif MS, Fakery AH, El-Agrody AM (2000) 4-Hydroxy coumarin in heterocy-clic synthesis. Part III: Synthesis of some new pyrano [2,3-d] [1,2,4] traizolo [1,5-c] pyrimidines and pyrimido [1,6-b] [1,2,4]–triazine derivatives. lLFarmaco 55:708–714CrossRefGoogle Scholar
  2. Bianchi G, Tava A (1987) Synthesis of (2R) (+)-2, 3-dihydro-2, 6-dimethyl-4H-pyran-one, a homologue of pheromones of a species in the hepialid family. Agric Biol Chem 51:2001–2002CrossRefGoogle Scholar
  3. Brown D, Katritzky AR, Rees CW (1984) Comprehensive heterocyclic chemistry 3. Pergamon Press, Oxford, p 443Google Scholar
  4. Buhl SN, Jackson KY (1978) Optimal conditions and comparison of lactate dehydrogenase catalysis of the lactate to pyruvate to lactate reactions in human serum at 25, 30 and 37°C. Clin Chem 24:828–835PubMedGoogle Scholar
  5. Dell CP, Smith CW (1993) Ant proliferative derivatives of 4H-naphtho [1, 2- b] pyran and process for their preparation. Eur Pat. 537:94, 9, 21; ref Chem Abstr (1993), 119, 139102dGoogle Scholar
  6. Domenjoz R, Schwarz (1952) Med Wochschr 82:1023Google Scholar
  7. Eiden F, Denk F (1991) Synthesis and CNS activity of pyrane derivatives: 6, 8-dioxa bicyclo (3, 2, 1)-octanes. Arch Pharm Weinheim Ger 324:353–354CrossRefGoogle Scholar
  8. El-Agrody AM, El-Hakim MH, Abd El-Latif MS, Fakery AH, El-Sayed EM, El-Ghareab KA (2000) Synthesis of pyrano[2,3-d]pyrimidine and pyrano[3,2-e] [1,2,4]traizolo[2,3-c]pyrimidine derivatives with promising antibacterial activities. Acta Pharm 50:111–120Google Scholar
  9. El-Agrody AM, Abd El-Latif MS, El-Hady NA, Fakery AH, Bedair AH (2001) Heteroaromatization with hydroxy coumarin. Part II: Synthesis of some new pyrano[2,3-d][1,2,4]traizolo [1,5-c] pyrimidines and pyrimido [1,6-b][1,2,4]-tri-azine derivatives. Molecules 6:519–527CrossRefGoogle Scholar
  10. El-Gaby MSA, Abdel-Gawad SM, Ghorab MM, Heiba HI, Aly HM (2006) Synthesis and biological activity of some novel thieno[2,3-b]quinoline, quinolino[3,2:4,5] thieno[3,2-d]pyrimidine and pyrido[2,3:4,5] thieno[2,3-b]quinoline derivatives. Phosphorus Sulfur Silicon 181:279–297CrossRefGoogle Scholar
  11. Fiala S, Fiala AE, Dixon B (1972) Gamma glutamyl transpeptidase in transplantable chemically induced rat hepatomas and spontaneous mouse hepatomas. J Natl Cancer Inst 48:1393PubMedGoogle Scholar
  12. Finney DJ (1964) Statistical methods in biological assay. Charles Griffen & Company Limit, LondonGoogle Scholar
  13. Hiramoto K, Nasuhara A, Michiloshi K, Kato T, Kikugawa K (1997) DNA strand-breaking activity and mutagenicity of 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one(DDMP). A Maillard reaction product of glucose and glycine. Mutat Res 395:47–56CrossRefPubMedGoogle Scholar
  14. Hren J, Po_zgan F, Buni CA, Parvulescu VI, Polanc S, Ko_cevar M (2009) An expeditious synthesis of b-pyrimidyl-a, b-didehydro-a-amino acid derivatives and pyrano[2,3-d]pyrimidines using microwave-assisted conditions. Tetrahedron 65:8216–8221CrossRefGoogle Scholar
  15. Hussein HEMA, Jamil K, Rao M (2001) Preliminary studies on the hypoglycemia effect of abromaaugustain alloxan diabetic rats. Ind J clin Biochem 16(1):77–80CrossRefGoogle Scholar
  16. Ismail ZH, Ghorab MM, Mohamed EMA, Aly HM, El-Gaby MSA (2008) Antitumor activity of some novel 1, 2, 5-thiadiazole derivatives. Phosphorus Sulfur Silicon 183:2541–2554CrossRefGoogle Scholar
  17. King EJ, Armstrong AR (1988) Calcium, phosphorus and phosphate. In: Varley H (ed) In practical clinical biochemistry. CBS Publishers, New Delhi, p 458Google Scholar
  18. Lavergne N, Volkman M, Maki JE, Yoder R, Trepanier LA (2005) Evaluation of the clinical, immunologic, and biochemical effects of sulfamethoxazole-nitroso administration to dogs: a pilot study. Toxicology 208:63–72CrossRefPubMedGoogle Scholar
  19. Marklund S, Marklund D (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–476CrossRefPubMedGoogle Scholar
  20. Martinez-Grau A, Marco LJ (1997) Friedlander reaction on 2-amino-3-cyano-4H-pyrans, synthesis of derivatives of 4H-pyran[2,3-b]quinoline, new tacrine analogues. Bioorg Med Chem Lett 7:3165–3170CrossRefGoogle Scholar
  21. Paglia D, Valentine W (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–164PubMedGoogle Scholar
  22. Prikazchikova LP, Khutova BM, Vladimirtsev IF, Boldyrev IV, Zhuravskaya NI (1975) Fiziol. Akt. Veshchestva. 7, 84. ref. Chem. Abstr. 83,127346 mGoogle Scholar
  23. Reitman S, Frankel A (1975) A colorimetric method for the determination of serum glutamic oxaloacetic acid and glutamic pyruvic transaminases. Am J Clin Pathol 28:56–62Google Scholar
  24. Selim YA, Ouf NH (2012) Anti-inflammatory new coumarin from the Ammi majus. L. Org Med Chem Lett 2(1):1–4PubMedCentralCrossRefPubMedGoogle Scholar
  25. Shishoo CJ, Devani MB, Ullas GV, Ananthan S, Bhadti VS (1981) Studies in the synthesis and interconversion of isomeric triazolopyrimidines. J Heterocycl Chem 18:43–46CrossRefGoogle Scholar
  26. Taylor R, Cleasby NA, Singh O, Skarzynski T, Wonacott AJ, Smith PW, Sollis SL, Howes PD, Cherry PC, Bethell R, Colman P, Varghese J (1998) Dihydropyrancarboxamides related to zanamivir: a new series of inhibitors of influenza virus sialidases. 2. Crystallographic and molecular modeling study of complexes of 4-amino-4H-pyran-6-carboxamides and sialidases from influenza virus types A and B. J Med Chem 41:798–807CrossRefPubMedGoogle Scholar
  27. Uchiyama M, Mihara M (1978) Determination of malonaldehyde precursor in tissues by thiobarbituric acid. Anal Biochem 86:271CrossRefPubMedGoogle Scholar
  28. Van Kampen EJ, Zijlstra WJ (1961) Standardization of hemoglobinometry II. The hemoglobin cyanide method. Clin Chim Acta 6:538–543CrossRefPubMedGoogle Scholar
  29. Yang JL, Jan MH, Chang CW, Lin JJ (2012) Effectiveness of the end-range mobilization and scapular mobilization approach in a subgroup of subjects with frozen shoulder syndrome: a randomized control trial. Man Ther 17(1):47–52CrossRefPubMedGoogle Scholar
  30. Yu J, Wang H, Hanqing (2005) Green synthesis of pyrano [2, 3-d]-pyrimidine derivatives in ionic liquids. Synth Commun 35:3133–3140CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • N. H. Ouf
    • 1
    • 2
  • Y. A. Selim
    • 3
    Email author
  • M. I. Sakran
    • 1
    • 4
  • A. S. Badr El-din
    • 1
    • 4
  1. 1.Department of Chemistry and Biochemistry, Faculty of ScienceTabuk UniversityTabukSaudi Arabia Kingdom
  2. 2.Department of Chemistry, Faculty of ScienceZagazig UniversityZagazigEgypt
  3. 3.Faculty of Specific EducationZagazig UniversityZagazigEgypt
  4. 4.Department of Chemistry, Faculty of ScienceTanta UniversityTantaEgypt

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