SYNTHESIS AND BIOLOGICAL PROPERTIES OF 1-(2-DEOXY-2-FLUORO-BETA-D-ARABINOFURANOSYL)URACIL

A novel 5-o-carboranyl-containing nucleoside, l-1-(2-deoxy-2-fluoro-be ta-D-arabinofuranosyl)urac il (6, CFAU), was synthesized as a potentia l intracellular neutron capture agent. This compound was prepared in f ive steps starting from 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)ur acil (1). The desired carboranyl derivative was obtained by addition o f decaborane [as the bis(propionitrile) adduct] to the protected acety lenic nucleoside precursor followed by debenzoylation. The synthesis o f CFAU was also performed by glycosylation of the suitably protected 5 -o-carboranyluracil with the appropriate 2-fluoroarabinosyl derivative . This compound was evaluated for its cytotoxicity in human lymphocyte s, monkey cells, and rat and human gliomas cells, as well as for antiv iral activity against human immunodeficiency virus and herpes simplex virus type 1. Its biological activity was compared to 5-o-carboranyl-1 -(2-deoxyribofuranosyl)uracil in these cell culture systems, human bon e marrow cells, and mice. The results obtained to date suggest that CF AU has suitable characteristics as a sensitizer for boron neutron capt ure therapy.