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. 1984 Jan 25;12(2):1179–1192. doi: 10.1093/nar/12.2.1179

Total synthesis of certain 2-, 6-mono- and 2,6-disubstituted-tubercidin derivatives. Synthesis of tubercidin via the sodium salt glycosylation procedure.

Z Kazimierczuk, G R Revankar, R K Robins
PMCID: PMC318564  PMID: 6694909

Abstract

Direct glycosylation of the sodium salt of 4,6-dichloro- or 4,6-dibromo-2-methylthiopyrrolo[2,3-d]pyrimidine with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide gave good yield of the corresponding N7-glycosylated pyrrolo [2,3-d]pyrimidine. The intermediate 4-amino-6-chloro-2-methylthio-7-beta-D-ribofuranosylpyrrolo[2,3-d] pyrimidine provided a new synthetic route to tubercidin, via 6-chlorotubercidin. 6-Chloro-2-methoxytubercidin was also obtained from 10 via the methylsulfone. Application of this glycosylation procedure to 4,6-dichloro- or 4,6-dibromo-2-methylpyrrolo [2,3-d]-pyrimidine also furnished the corresponding N7-glycosyl derivatives with beta-configuration. Dehalogenation of gave 2-methyl-tubercidin and bromination with bromine in a buffered solution gave 5,6-dihalo-2-methyltubercidin. Several new 2,6-disubstituted tubercidin derivatives were prepared from these glycosyl intermediates. This new sodium salt glycosylation procedure was found to be superior to other procedures for the total synthesis of these halogenated 7-deazapurine nucleosides.

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Selected References

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  1. BHUYAN B. K., RENIS H. E., SMITH C. G. A collagen plate assay for cytotoxic agents. II. Biological studies. Cancer Res. 1962 Oct;22:1131–1136. [PubMed] [Google Scholar]
  2. Bergstrom D. E., Brattesani A. J. Halogenation of tubercidin by N-halosuccinimides. A direct route to 5-bromotubercidin, a reversible inhibitor of RNA synthesis in eukaryotic cells. Nucleic Acids Res. 1980 Dec 20;8(24):6213–6219. doi: 10.1093/nar/8.24.6213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bobek M., Whistler R. L., Bloch A. A. Synthesis and biological activity of 4'-thio analogs of the antibiotic toyocamycin. J Med Chem. 1972 Feb;15(2):168–171. doi: 10.1021/jm00272a011. [DOI] [PubMed] [Google Scholar]
  4. DUVALL L. R. TUBERCIDIN. Cancer Chemother Rep. 1963 Jul;30:61–62. [PubMed] [Google Scholar]
  5. Grage T. B., Rochlin D. B., Weiss A. J., Wilson W. L. Clinical studies with tubercidin administered after absorption into human erythrocytes. Cancer Res. 1970 Jan;30(1):79–81. [PubMed] [Google Scholar]
  6. Mizuno Y., Ikehara M., Watanabe K., Suzaki S. Structural elucidation of tubercidin. Chem Pharm Bull (Tokyo) 1963 Aug;11(8):1091–1094. doi: 10.1248/cpb.11.1091. [DOI] [PubMed] [Google Scholar]
  7. OWEN S. P., SMITH C. G. CYTOTOXICITY AND ANTITUMOR PROPERTIES OF THE ABNORMAL NUCLEOSIDE TUBERCIDIN (NSC-56408). Cancer Chemother Rep. 1964 Mar;36:19–22. [PubMed] [Google Scholar]
  8. RENIS H. E., JOHNSON H. G., BHUYAN B. K. A collagen plate assay for cytotoxic agents. I. Methods. Cancer Res. 1962 Oct;22:1126–1130. [PubMed] [Google Scholar]
  9. SMITH C. G., LUMMIS W. L., GRADY J. E. An improved tissue culture assay. II. Cytotoxicity studies with antibiotics, chemicals, and solvents. Cancer Res. 1959 Sep;19:847–852. [PubMed] [Google Scholar]
  10. Stevens J. D., Ness R. K., Fletcher H. G., Jr Syntheses with partially benzylated sugars. XI. Studies on the synthesis of the anomeric 5,6-dimethyl-1-D-ribofuranosylbenzimidazoles (ribazoles). Comparison of the condensation of 2,3,5-tri-O)-benzoyl-D-ribofuranosyl bromide and 2,3,5-tri-O-benzyl-D-ribofuranosyl chloride with 5,6-dimethylbenzimidazole. J Org Chem. 1968 May;33(5):1806–1810. doi: 10.1021/jo01269a022. [DOI] [PubMed] [Google Scholar]
  11. Tolman R. L., Robins R. K., Townsend L. B. Pyrrolo[2,3-d]pyrimidine nucleoside antibiotics. Total synthesis and structure of toyocamycin, unamycin B, vengicide, antibiotic E-212, and Sangivamycin (BA-90912). J Am Chem Soc. 1968 Jan 17;90(2):524–526. doi: 10.1021/ja01004a076. [DOI] [PubMed] [Google Scholar]
  12. Tolman R. L., Robins R. K., Townsend L. B. Pyrrolopyrimidine nucleosides. 3. The total synthesis of toyocamycin, sangivamycin, tubercidin, and related derivatives. J Am Chem Soc. 1969 Apr 9;91(8):2102–2108. doi: 10.1021/ja01036a040. [DOI] [PubMed] [Google Scholar]
  13. Wolberg W. H. Effect of tubercidin on nucleoside incorporation in human tumors. Biochem Pharmacol. 1965 Dec;14(12):1921–1925. doi: 10.1016/0006-2952(65)90290-x. [DOI] [PubMed] [Google Scholar]

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