Novel Carboranyl Diols and Their Derived Phosphate Esters

  • Robert R. Kane
  • Christine S. Lee
  • Cindy L. Coe
  • Melissa A. St. Rose
  • Karin Drechsel
  • M. Frederick Hawthorne


Tumor-directed antibodies or their immunoreactive fragments are attractive candidates for the selective delivery of 10B for BNCT, provided that ~1000 10B atoms can be attached to each immunoreactive protein without significantly altering its biological properties. 1 Previous studies have revealed problems associated with randomly conjugating whole monoclonal antibodies (MAbs) with large numbers of small boron-containing compounds 2 or with limited numbers of heterogeneous 3 or homogeneous boron-rich polymers. 4 Recently, we have described an approach to this problem based on the synthesis of a homogeneous boron-rich ‘trailer’ compound and it’s conjugation to a specific site of a tumor-directed antibody fragment (Fab-SH). 5 The success of this approach rests upon the ability to precisely synthesize a hydrophilic “trailer” molecule containing ~1000 10B atoms. An oligophosphatebased boronated “trailer” is an attractive target, as the requisite coupling chemistry is well developed (in the context of DNA synthesis 6) and the polyanionic oligomers would be expected to be inherently hydrophilic. We report herein preliminary results concerning the solution-phase synthesis of hydrophilic boron-rich oligophosphates, novel compounds that may find utility as intermediates in the assembly of tumor-localizing boron-rich compounds. 7


Selective Delivery Carborane Derivative Label Biomolecule Polyanionic Oligomer Immunoreactive Fragment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    It can be calculated that antibodies with this load of10B would deliver ∼30 ppm 10B in tumor.Google Scholar
  2. 2.
    Mizusawa, E.; Dahlman, H.L.; Bennett, S.J.; Goldenberg, D.M.; Hawthorne, M.F. (1982) Proc, Nat. Acad. Sci. U.S.A. 79 3011–3014. Goldenberg, D.M.; Sharkey, R.M.; Primius, F.J.; Mizusawa, E.; Hawthorne, M.F. (1984) Proc,Nat. Acad. Sci. U.S.A. 81 560–563. Mizusawa, E.; Thompson, M.R.; Hawthorne, M.F. (1985) Inorg. Chem. 24 1911–1916.Google Scholar
  3. 3.
    For example, see: Alam, F.; Soloway, A.H.; Barth, R.F.; Mafune, N.; Adams, D.M.; Knoth, W.H. (1989) J. Med. Chem. 32 2326–2330. Pettersson, M.L.; Courel, M.-N.; Girard, N.; Gabel, D.; Delpech, B. (1989) Strahlenther Oncol. 165(2/3) 151–152.Google Scholar
  4. 4.
    Varadarajan, A.; Hawthorne, M.F. (1981) Bioconjugate Chem. 2(4) 242–253. Paxton, R.J.; Beatty, B.G.; Varadarajan, A.; Hawthorne, M.F. (1992) Bioconjugate Chem. 3(3) 241–247.Google Scholar
  5. 5.
    Hawthorne, M.F. (1991) Pure and Appl. Chem. 24 327–334.CrossRefGoogle Scholar
  6. 6.
    Gait, M.J. (ed.) Oligonucleotide Synthesis: A Practical Approach; IRL, Ltd.: Oxford, 1984.Google Scholar
  7. 7.
    Some of these results were presented at the 203rd National Meeting of the American Chemical Society (ORGN#242).Google Scholar
  8. 8.
    Throughout this paper closo-carborane, o-carborane, or carboranyl refer to derivatives of the closo-1, 2-C2B 10H12 cage, while nido-carborane refers to derivatives of the [nido-7,8-C2B9H11]- cage fragment.Google Scholar
  9. 9.
    For example, see Grimes, R.N. Carboranes Academic Press, New York: 1970.Google Scholar
  10. 10.
    Hawthorne, M.F.; Wegner, P.A.; Stafford, R.C. (1965) Inorg. Chem. 4 1675. Wiesboeck, R.A.; Hawthorne, M.F. (1964) J. Am. Chem. Soc. 86 1643–1644.Google Scholar
  11. 11.
    Yields are reported for material homogeneous by NMR, TLC and/or HPLC. All new compounds reported in this communication have been appropriately characterized (HRMS, HPLC, multinuclear NMR, etc.).Google Scholar
  12. 12.
    Key NMR data for compound 3: 1H (200 MHz, CD3OD) δ 3.56 (triplet, J=5.9 Hz, 4 H), 2.37 (aa’bb’ pattern, 4 H), 1.83–1.69 (multiplet, 4 H); 13C (50 MHz, CD3OD) δ 81.35, 61.48, 33.62, 32.60; 11B (160 MHz, CD3OD) δ –4.44 (doublet, J B-H=146.0, 2 B), -8.91(doublet, J B-H=153.7, 2 B), -10.09(doublet, J B-H=161.4, 6 B). Google Scholar
  13. 13.
    A 3:1:1 mixture of acetic acid: tetrahydrofuran: water was added to the silylprotected alcohol and the mixture was stirred at room temperature until all the starting material was dissolved (~4 hours). Corey, E.J. (1972) J. Am. Chem. Soc. 94, 6190–6192. Attempted deprotection of 4 with TBAF resulted in the formation of an intractable mixture of products.Google Scholar
  14. 14.
    Reese, C.B.; Titmas, R.C.; Yau, L. (1978) Tetrahedron Lett. (30) 2727–2730.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Robert R. Kane
    • 1
  • Christine S. Lee
    • 1
  • Cindy L. Coe
    • 1
  • Melissa A. St. Rose
    • 1
  • Karin Drechsel
    • 2
  • M. Frederick Hawthorne
  1. 1.University of California at Los AngelesLos AngelesUSA
  2. 2.On leave from Institut für Anorganische Chemie der TechnischenHochschule AachenAachenGermany

Personalised recommendations