Enantioselective Syntheses of 10B-Enriched L- and D-Carboranylalanine and Their Radiobiological Evaluation in V-79 Chinese Hamster Cells

  • Stephen B. Kahl
  • John J. Schaeck
  • Brenda Laster
  • Lynn Warkentien

Abstract

The single greatest impediment to widespread clinical use of BNCT is the development of boron compounds that deliver large amounts of boron to the tumor, are highly tumor selective while clearing from normal tissues and blood, and which have acceptably low systemic toxicity. Boronated amino acids represent one potentially useful approach to meeting these requirements. While BPA possesses some of these very desirable characteristics, its single boron atom and lack of significant aqueous solubility requires that very large doses of the fructose complex be administered to achieve minimal acceptable tumor boron and tumor:normal tissue ratios. Amino acids bearing the polyhedral carbo-rane cage represent a potential source of compounds which, either in and of themselves or in a small tumor-seeking peptide, might provide alternatives to BPA. The carborane analog of phenylalanine, carboranylalanine or Car, has received special attention in this regard. First synthesized by Zakharkin et al.1 and by Brattsev and coworkers2 and later by Soloway’s group as the racemic mixture,3 Car has more recently been prepaid stereoselectively.4, 5, 6 Our group was the first to publish a truly stereoselective method of preparation by which both enantiomers could be made available.7 Beginning with allyl-o-carborane and following an oxazolidinone approach pioneered by Evans et al.,8 the 6 step synthesis produced either L- or D-Car in about 34% overall yield.

Keywords

Boron Alkyne Phenylalanine Benzyl Azide 

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Stephen B. Kahl
    • 1
  • John J. Schaeck
    • 1
  • Brenda Laster
    • 2
  • Lynn Warkentien
    • 2
  1. 1.Department of Pharmaceutical ChemistryUniversity of CaliforniaSan FranciscoUSA
  2. 2.Medical DepartmentBrookhaven National LaboratoryUSA

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