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. 1987 Feb 11;15(3):1217–1226. doi: 10.1093/nar/15.3.1217

2'-Deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl) and 1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor.

N S Girgis, H B Cottam, S B Larson, R K Robins
PMCID: PMC340519  PMID: 3593477

Abstract

The synthesis of two new analogs of 2'-deoxyguanosine, 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c] pyridin-4(5H)-one (8) and 6-amino-1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (13) has been accomplished by glycosylation of the sodium salt of ethyl 2-cyanomethyl-1H-pyrrole-3-carboxylate (4c) using 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose( 5) and 1-chloro-2,3,5-tri-O-benzyl-alpha-D-arabinofuranose (9), respectively. The resulting blocked nucleosides, ethyl 2-cyanomethyl-1-(2-deoxy-3,5-di-O-p-toluoyl-beta-D-erythro- pentofuranosyl)-1H-pyrrole-3-carboxylate (6) and ethyl 2-cyanomethyl-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)- 1H-pyrrole-3-carboxylate, were ring closed with hydrazine to form 5-amino-6-hydrazino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H- pyrrolo[3,2-c]-pyridin-4(5H)-one (7) and 5,6-diamino-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-1H- pyrrolo[3,2-c]pyridin-4(5H)-one (11), respectively. Treatment of 7 with Raney nickel provided the 2'-deoxyguanosine analog 8 while reaction of 11 with Raney nickel followed by palladium hydroxide/cyclohexene treatment gave the 2'-deoxyguanosine analog 13. The anomeric configuration of 8 was assigned as beta by proton NMR, while that of 13 was confirmed as beta by single-crystal X-ray analysis of the deblocked precursor ethyl 2-cyanomethyl-1-beta-D-arabinofuranosyl-1H-pyrrole-3-carboxylate (10a).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cottam H. B., Kazimierczuk Z., Geary S., McKernan P. A., Revankar G. R., Robins R. K. Synthesis and biological activity of certain 6-substituted and 2,6-disubstituted 2'-deoxytubercidins prepared via the stereospecific sodium salt glycosylation procedure. J Med Chem. 1985 Oct;28(10):1461–1467. doi: 10.1021/jm00148a015. [DOI] [PubMed] [Google Scholar]
  2. Preobrazhenskaya M. N., Vigdorchik M. M., Suvorov N. N. Glycosylindoles. VII. Synthesis of 1-(D-beta-ribofuranosyl)indole. Tetrahedron. 1967 Dec;23(12):4653–4660. doi: 10.1016/s0040-4020(01)92563-3. [DOI] [PubMed] [Google Scholar]
  3. Revankar G. R., Gupta P. K., Adams A. D., Dalley N. K., McKernan P. A., Cook P. D., Canonico P. G., Robins R. K. Synthesis and antiviral/antitumor activities of certain 3-deazaguanine nucleosides and nucleotides. J Med Chem. 1984 Nov;27(11):1389–1396. doi: 10.1021/jm00377a002. [DOI] [PubMed] [Google Scholar]
  4. Robins M. J., Robins R. K. Purine nucleosides. XI. The synthesis of 2'-deoxy-9-alpha- and-beta-D-ribofuranosylpurines and the correlation of their anomeric structure with proton magnetic resonance spectra. J Am Chem Soc. 1965 Nov 5;87(21):4934–4940. doi: 10.1021/ja00949a042. [DOI] [PubMed] [Google Scholar]
  5. Schneller S. W., Hosmane R. S., MacCartney L. B., Hessinger D. A. Synthesis and xanthine oxidase inhibitory analysis of 1H-pyrrolo[3,2-c]pyridine-4,6(5H,7H)-dione (3,7-dideazaxanthine) and two of its derivatives. J Med Chem. 1978 Sep;21(9):990–993. doi: 10.1021/jm00207a028. [DOI] [PubMed] [Google Scholar]
  6. Walton E., Holly F. W., Jenkins S. R. Indole and 4-aminoindole nucleosides. J Org Chem. 1968 Jan;33(1):192–197. doi: 10.1021/jo01265a602. [DOI] [PubMed] [Google Scholar]

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