Synthesis of a Water-Soluble o-Carborane Bearing Uracil Moiety Via Palladium Catalyzed Reaction under Essentially Neutral Conditions

  • Hisao Nemoto
  • Jianping Cai
  • Yoshinori Yamamoto


Although the icosahedral boron cluster, dodecaboranethiol (1), has been used clinically1 as a boron carrier for boron neutron capture therapy (BNCT), we still need to enhance the efficiency and selectivity of boron uptake by cancer cells. Therefore, a number of synthetic studies of boron carriers2~7 containing the similar cluster, o-carborane (2) have been recently reported (Figure 1).


Boron Neutron Capture Therapy Boron Uptake Methyl Chloroformate Allyl Carbonate Cascade Type 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. Hatanaka, K. Sano, and H. Yasukochi, “Progress in Neutron Capture Therapy for Cancer, B. J. Allen, D. E. Moore, B. V. Harrington ed., Plenum Press, New York, 1992, pp. 561–568.; M. F. Hawthorne, The role of chemistry in the development of boron neutron capture therapy of cancer, Angew. Chem. Internat. Ed. Engl. 32: 950–984 (1993).Google Scholar
  2. 2.
    Y. Yamamoto, T. Seko, H. Nakamura, H. Nemoto, H. Hojo, N. Mukai and Y. Hashimoto, Synthesis of carboranes containing nucleoside bases. Unexpectedly high cytostatic and cytocidal toxicity toward cancer cells, J. Chem. Soc., Chem. Commun., 157- (1992).Google Scholar
  3. 3.
    Y. Yamamoto, T. Seko, H. Nakamura and H. Nemoto, Synthesis of carboranes containing nucleoside bases, Heteroatom Chem., 3: 239–244 (1992).CrossRefGoogle Scholar
  4. 4.
    H. Kets, W. Tjarks, and D. Gabel, Synthesis of nido-carborane containing thioureas, Tetrahedron Lett., 31: 4003–4006 (1990).CrossRefGoogle Scholar
  5. 5.
    J. L. Maurer, F. Berthier, A. J. Serino, C. B. Knobler and M. F. Hawthorne, Glycosylcarborane derivatives and the determination of the absolute configuration of a diastereomeric triol from X-ray diffraction, J. Org. Chem., 55: 838–843 (1990).CrossRefGoogle Scholar
  6. 6.
    S. B. Kahl, and M.-S. Koo, Synthesis of tetrakiscarborane-carboxylate esters of 2,4- bis(a,ßdihydroxyethyl)-deuteroporphyrin IX, J. Chem. Soc., Chem. Commun.,1769–1771 (1990).Google Scholar
  7. 7.
    A. K. M. Anisuzzaman, F. Alam, and A. H. Soloway, Synthesis of a carboranyl nucleoside for potential use in neutron capture therapy, Polyhedron, 9: 891–892 (1990).CrossRefGoogle Scholar
  8. 8.
    M. Takagaki, Y. Oda, Z. H. Zhen and H. Kikuchi (Department of Neurosurgery, Faculty of Medicine, Kyoto University), Unpublished results.Google Scholar
  9. 9.
    H. Nemoto, J. G. Wilson, H. Nakamura and Y. Yamamoto, Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy, J. Org. Chem., 57: 435–435 (1992).Google Scholar
  10. 10.
    H. Nemoto, F-G. Rong and Y. Yamamoto, The first alkylation of o-carboranes under essentially neutral conditions. Application to the synthesis of 10B carriers, J. Org. Chem.,55:6065- (1990). The previous allylation of carboranes was carried out with those having an electron withdrawing group at the carbon terminus.Google Scholar
  11. 11.
    Regiochemistry of allylations via palladium catalysts is dependent upon the substrates, leaving groups, phosphine ligands, and nucleophiles. J. Tsuji, Catalytic Reactions via t-allylpalladium complexes, Pure and Appl. Chem., 54: 197–206 (1982).CrossRefGoogle Scholar
  12. 12.
    The simple allylation of o-carboranes proceeded very well at room temperature.10 Google Scholar
  13. 13.
    Preparation of 8 R. F. Schinazi and W. H. Prusoff, Synthesis of 5-(dihydroxyboryl)-2’- deoxyuridine and related boron-containing pyrimidines, J. Org. Chem.,50:841–847 (1985).Google Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Hisao Nemoto
    • 1
  • Jianping Cai
    • 1
  • Yoshinori Yamamoto
    • 2
  1. 1.Department of Applied Molecular ScienceInstitute for Molecular Science, Okazaki National Research InstitutesOkazaki, Aichi 444Japan
  2. 2.Department of Chemistry, Faculty of ScienceTohoku UniversityJapan

Personalised recommendations