The synthesis of a tricyclic system with the 7-deazaadenine nucleus

Authors

  • L. V. Muzychka Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • I. O. Yaremchuk Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • Ye. V. Verves Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. B. Smolii Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.18.936

Keywords:

pyrrolo[2, 3-d]pyrimidine, 7-deazaadenine, iodolactonization, 1-deazapyrimido[1, 2, 3-cd]purine

Abstract

Aim. To develop new convenient approaches to the synthesis of new tricyclic compounds with the 7-deazaadenine nucleus as promising synthons for the search of biologically active compounds.
Results and discussion. A new simple approach to the synthesis of 4-amino substituted pyrrolo[2,3-d]pyrimidine-6-carboxylic acids was found. A tricyclic derivative of 7-deazadenine was obtained by the intramolecular cyclization of methyl 7-oxiranylmethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate.
Experimental part. Treatment of 4-methoxypyrrolo[2,3-d]pyrimidine with ammonium acetate while heating leads to 4-aminopyrolo[2,3-d]pyrimidine-6-carboxylic acid. This acid reacts with iodine in acetic acid producing 8-iodomethylpyrimido[5’,4’:4,5]pyrrolo[2,1-c][1,4]oxazine with a high yield. Treatment of oxazine with sodium methylate gives 7-(oxiran-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate; when it is heated with triethylamine hydrochloride in acetonitrile, 10-amino-5,6-dihydro-4H-1-deazapyrimido[1,2,3-cd]purine-2-carboxylate previously unknown is obtained. The structure and composition of the substances obtained were confirmed by NMR-spectroscopy, chromatography mass-spectrometry and elemental analysis.
Conclusions. A new convenient approach to the synthesis of 10-amino-5,6-dihydro-4H-1-deazapyrimido[1,2,3-cd]purine-2-carboxylate has been developed. This compound is a tricyclic system with the 7-deazaadenine nucleus. Its further modification may produce potential biologically active substances.

Downloads

Download data is not yet available.

References

  1. Adel, M., Serya, R. A. T., Lasheen, D. S., Abouzid, K. A. M. (2018). Pyrrolopyrimidine: a versatile scaffold for construction of targeted anti–cancer agents. Journal of Advanced Pharmacy Research, 2 (1), 1–19.
  2. Perlíková, P., Eberlin, L., Ménová, P., Raindlová, V., Slavětínská, L., Tloušťová, E., Hocek, M. (2013). Synthesis and Cytostatic and Antiviral Activities of 2’–Deoxy–2’,2’–difluororibo– and 2’–Deoxy–2’–fluororibonucleosides Derived from 7–(Het)aryl–7–deazaadenines. ChemMedChem, 8 (5), 832–846. doi: 10.1002/cmdc.201300047
  3. Bio, M. M., Xu, F., Waters, M., Williams, J. M., Savary, K. A., Cowden, C. J., Grabowski, E. J. J. (2004). Practical Synthesis of a Potent Hepatitis C Virus RNA Replication Inhibitor. The Journal of Organic Chemistry, 69 (19), 6257–6266. doi: 10.1021/jo0491096
  4. Eldrup, A. B., Prhavc, M., Brooks, J., Bhat, B., Prakash, T. P., Song, Q., Olsen, D. B. (2004). Structure−Activity Relationship of Heterobase–Modified 2‘–C–Methyl Ribonucleosides as Inhibitors of Hepatitis C Virus RNA Replication. Journal of Medicinal Chemistry, 47 (21), 5284–5297. doi: 10.1021/jm040068f
  5. Kim, H.–J., Sharon, A., Bal, C., Wang, J., Allu, M., Huang, Z., Chu, C. K. (2009). Synthesis and Anti–Hepatitis B Virus and Anti–Hepatitis C Virus Activities of 7–Deazaneplanocin A Analogues in Vitro. Journal of Medicinal Chemistry, 52 (1), 206–213. doi: 10.1021/jm801418v
  6. Arumugham, B., Kim, H.–J., Prichard, M. N., Kern, E. R., Chu, C. K. (2006). Synthesis and antiviral activity of 7–deazaneplanocin A against orthopoxviruses (vaccinia and cowpox virus). Bioorganic & Medicinal Chemistry Letters, 16 (2), 285–287. doi: 10.1016/j.bmcl.2005.10.007
  7. Arcari, J. T., Beebe, J. S., Berliner, M. A., Bernardo, V., Boehm, M., Borzillo, G. V., Chen, J. M. (2013). Discovery and synthesis of novel 4–aminopyrrolopyrimidine Tie–2 kinase inhibitors for the treatment of solid tumors. Bioorganic & Medicinal Chemistry Letters, 23 (10), 3059–3063. doi: 10.1016/j.bmcl.2013.03.012
  8. Fairhurst, R. A., Marsilje, T. H., Stutz, S., Boos, A., Niklaus, M., Chen, B., Jeay, S. (2016). Optimisation of a 5–[3–phenyl–(2–cyclic–ether)–methyl–ether]–4– aminopyrrolopyrimidine series of IGF–1R inhibitors. Bioorganic & Medicinal Chemistry Letters, 26 (8), 2057–2064. doi: 10.1016/j.bmcl.2016.02.075
  9. Calderwood, D. J., Johnston, D. N., Munschauer, R., Rafferty, P. (2002). Pyrrolo[2,3–d]pyrimidines containing diverse N–7 substituents as potent inhibitors of Lck. Bioorganic & Medicinal Chemistry Letters, 12 (12), 1683–1686. doi: 10.1016/s0960–894x(02)00195–6
  10. Murphy, S. T., Alton, G., Bailey, S., Baxi, S. M., Burke, B. J., Chappie, T. A., Yu, X.–H. (2011). Discovery of Novel, Potent, and Selective Inhibitors of 3–Phosphoinositide–Dependent Kinase (PDK1). Journal of Medicinal Chemistry, 54 (24), 8490–8500. doi: 10.1021/jm201019k
  11. Verves, E. V., Kucher, A. V., Muzychka, L. V., Smolii, O. B. (2013). Synthesis of 7–alkyl–4–amino–7H–pyrrolo–[2,3–d]pyrimidine–6–carboxylic acids. Chemistry of Heterocyclic Compounds, 48 (12), 1844–1852. doi: 10.1007/s10593–013–1218–0
  12. Mizuno, Y., Ikehara, M., Watanabe, K. A., Suzaki, S., Itoh, T. (1963). Synthetic Studies of Potential Antimetabolites. IX. The Anomeric Configuration of Tubercidin. The Journal of Organic Chemistry, 28 (12), 3329–3331. doi: 10.1021/jo01047a012
  13. Seden, T. P., Turner, R. W. (1975). The reaction of adenine with epichlorohydrin. Journal of Heterocyclic Chemistry, 12 (5), 1045–1046. doi: 10.1002/jhet.5570120548
  14. Sund, P., Kronberg, L. (2008). Ring–Opening of 3–β–D–Ribofuranosyl–3,7,8,9–Tetrahydropyrimido [1,2–i]Purin–8–ol and Preparation of 2–Thio–
  15. and 2–aza–Adenosine Derivatives. Nucleosides, Nucleotides and Nucleic Acids, 27 (12), 1215–1226. doi: 10.1080/15257770802458162
  16. Burbiel, J. C., Hockemeyer, J., Müller, C. E. (2006). Microwave–assisted ring closure reactions: synthesis of 8–substituted xanthine derivatives and related pyrimido– and diazepinopurinediones. Beilstein Journal of Organic Chemistry, 2 (1), 20. doi: 10.1186/1860–5397–2–20
  17. Weyler, S., Fülle, F., Diekmann, M., Schumacher, B., Hinz, S., Klotz, K.–N., Müller, C. E. (2006). Improving Potency, Selectivity, and Water Solubility of Adenosine A1 Receptor Antagonists: Xanthines Modified at Position 3 and Related Pyrimido[1,2,3–cd]purinediones. ChemMedChem, 1 (8),
  18. –902. doi: 10.1002/cmdc.200600066
  19. Mieczkowski, A., Roy, V., Agrofoglio, L. A. (2010). Preparation of Cyclonucleosides. Chemical Reviews, 110 (4), 1828–1856. doi: 10.1021/cr900329y
  20. De Carvalho, G. S. G., Fourrey, J.–L., Dodd, R. H., Da Silva, A. D. (2009). Synthesis of a 4’,4’–spirothietane–2’, N3–cycloadenosine as a highly constrained analogue of 5’–deoxy–5’–methylthioadenosine (MTA). Tetrahedron Letters, 50 (4), 463–466. doi: 10.1016/j.tetlet.2008.11.039

Downloads

Published

2018-03-14

How to Cite

(1)
Muzychka, L. V.; Yaremchuk, I. O.; Verves, Y. V.; Smolii, O. B. The Synthesis of a Tricyclic System With the 7-Deazaadenine Nucleus. J. Org. Pharm. Chem. 2018, 16, 28-33.

Issue

Vol. 16 No. 1(61) (2018)

Section

Original Researches

License

Copyright (c) 2018 National University of Pharmacy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors publishing their works in the Journal of Organic and Pharmaceutical Chemistry agree with the following terms:

1. Authors retain copyright and grant the journal the right of the first publication of the work under Creative Commons Attribution License allowing everyone to distribute and re-use the published material if proper citation of the original publication is given.

2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal’s published version of the work (e.g., post it to an institutional repository or publish it in a book) providing proper citation of the original publication.

3. Authors are permitted and encouraged to post their work online (e.g. in institutional repositories or on authors’ personal websites) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (see The Effect of Open Access).