Enantioselective Syntheses of 10B-Enriched L- and D-Carboranylalanine and Their Radiobiological Evaluation in V-79 Chinese Hamster Cells
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.
KeywordsChinese Hamster Cell Hydrochloride Salt Benzyl Ester Dose Enhancement Enantioselective Synthesis
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- 1.L.I. Zakharkin, A.V. Grebennikov, and A.I. L’vov Izv. Akad. Nauk, SSSR Ser. Khim. 106–112 (1970).Google Scholar
- 2.V.A. Brattsev, and V.I. Stanko Zh. Obshch. Khim. 39, 1175–6 (1969).Google Scholar
- 5.S. Sjöberg, J. Carlsson, P. Lindstrom, and J. Malmquist Current Topics in the Chemistry of Boron; G.W. Kabalka, Ed; Royal Society of Chemistry: Cambridge, U.K. pp. 172–176 (1994).Google Scholar