Tumour-targetted boranes. Part 2. Coupling of closo-carboranes to substituted 2-nitroimidazoles via 1,3-dipolar cycloaddition

Abstract

Carboranes targetted to specific tumour tissues are important for boron neutron capture therapy of cancer. Direct syntheses of carboranes linked to 2-nitroimidazole were unsuccessful. A mild procedure for 1, 3-dipolar cycloaddition of 4-(carboranylmethoxy)benzonitrile N-oxide 32 with a nitroimidazolyl-alkene 27 and with nitroimidazolyl-alkynes 3 and 30 has been developed, using a series of model reactions, yielding a dihydroisoxazole 28 and the isoxazoles 29 and 31, respectively. The nitrite oxide 32 is unusually stable. Dithioacetals are shown to be suitable protecting groups for aromatic aldehydes under the vigorous reductive and Lewis acidic-basic conditions of carborane formation. 6- Methoxy-4H-[1] benzopyrano [4,3-c] isoxazole 16 has been synthesised by intramolecular 1,3-dipolar cycloaddition. The structure of the isoxazole derivative 29 has been confirmed by an X-ray crystal structure analysis.