TUMOR-TARGETED BORANES .2. COUPLING OF CLOSO-CARBORANES TO SUBSTITUTED 2-NITROIMIDAZOLES VIA 1,3-DIPOLAR CYCLOADDITION

Carboranes targetted to specific tumour tissues are important for boro n neutron capture therapy of cancer. Direct syntheses of carboranes li nked to 2-nitroimidazole were unsuccessful. A mild procedure for 1,3-d ipolar cycloaddition of 4-(carboranylmethoxy)benzonitrile N-oxide 32 w ith 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 and31. respectively. The nit rile oxide 32 is unusually stable. Dithioacetals are shown to be suita ble protecting groups for aromatic aldehydes under the vigorous reduct ive and Lewis acidic-basic conditions,of carborane formation. 6-Methox y-4H-[1]benzopyrano[4,3-c]isoxazole 16 been synthesised by intramolecu lar 1,3-dipolar cycloaddition. The structure of-the isoxazole derivati ve 29 has been confirmed by an X-ray crystal structure analysis.