Asymmetric Synthesis of o- and p-Carboranyl Amino Acids
The amino acid p-boronophenylalanine (BPA) containing one boron atom is presently of considerable clinical interest for use in BNCT of cancer. Amino acids, substituted with polyhedral boron clusters, could also be of interest for BNCT.1a–k We have recently reported the synthesis of some amines and optically active amino acids, containing the lipophilic o-carborane cage1b,e In this contribution we describe the synthesis of the hydrophilically substituted o-carborane derivatives, the diolamine 3 (DAC-1) and the diolamino acid 7 (DAAC-1) as well as the asymmetric synthesis of the highly lipophilic amino acid p-carboranylalanine 14. A method for determination of enantiomeric purities of o-carboranylalanine using supercritical fluid chromatography (SFC) on a β-cyclodextrin based stationary phase is reported.
KeywordsBoron Atom Chiral Selectivity Boron Neutron Capture Therapy Asymmetric Synthesis Supercritical Fluid Chromatography
Unable to display preview. Download preview PDF.
- 1.a)P. Lindström, Boron neutron capture therapy. Synthesis of boron containing substances and tests of their binding and toxicity, Doctoral Dissertation, Acta Univ. Uppsaliensis 32, 1994.Google Scholar
- S. Sjöberg, M.F. Hawthorne, P. Lindström, J. Malmquist, J. Carlsson, A. Andersson, and O. Pettersson, Asymmetric synthesis of carboranyl amino acids with potential use in BNCT, in: “Advances in Neutron Capture Therapy”, Barth, R.F.; Carpenter, D.E.; Soloway, A.H., Eds.; Plenum: New York, 1993, pp. 269–273.CrossRefGoogle Scholar
- c).P. Radel and S.B. Kahl, Enantioselective synthesis of an unnatural amino acid, L-carboranylalanine. ibid; pp 277–280.Google Scholar
- e).S. Sjöberg, J. Carlsson, P. Lindström, and J. Malmquist, Carboranyl amino acids and amines with potential use in BNCT. Current Topic in the Chemistry of Boron, Kabalka, G. W., Ed. The Royal Society of Chemistry, 1994, pp. 173–176.Google Scholar
- h).J.-L. Fauchère, O. Leukart, A. Eberle, and R. Scwyzer, The synthesis of(4-carboranylalanine, 5-leucine)-enkephalin, Hel: Chim. Acta 629: 1386–1395, 1979.Google Scholar
- j).L.I. Zakharkin, A.V. Grbenikov, and A.I. L’vov, Synthesis of some nitrogenous barene derivatives, Izv. Akad. Nauk SSSR, Ser Khim. 1: 106–112, 1970.Google Scholar
- k).V.A Brattsev and V.I. Stanko, (3-(o-Barenyl)alanine, Zh. Ohshch Khim. 39: 1175–1176, 1969.Google Scholar
- 4.P. Lindström, P. Olsson, J. Malmquist, J. Petterssson, P. Lemmen. S. Sjöberg, A. Olin, J. Carlsson, New carborane based compounds for boron neutron capture therapy: binding and toxicity of ANC-1, DAC-I and B-Et-11-OMe in cultured glioma and mouse melanoma cells, Anti Cancer Drugs 5: 43–52, 1994PubMedCrossRefGoogle Scholar
- 5.P. Olsson, P. Lindström, N. Tilly, M. Black, J. Malmquist, S. Sjöberg, and J. Carlsson, Uptake and biological effects of the carborane based compounds DAC-1 and DAAC-I, In this proceedings.Google Scholar
- 8.A. Harada and S. Takahashi, Preparation and properties of inclusion complexes of 1,2-dicarbadodecaborane(12) with cyclodextrins, J. Chem. Soc. Chem. Commun. 1352–1353, 1989.Google Scholar