Synthesis of 5-(Dihydroxyboryl)-2'-deoxyuridine and Related Boron-Containing Pyrimidines

Article abstract of DOI:10.1021/jo00206a024

Organoboron derivatives of pyrimidines and of 2'-deoxyribonucleosides have been synthesized as potential antiviral and anticancer agents.The first 5-boron-substituted pyrimidine nucleoside, 5-(dihydroxyboryl)-2'-deoxyuridine, has been prepared via a metal-halogen exchange at -50 deg C in tetrahydrofuran on 5-bromo-3',5'-bis (O-trimethylsilyl)-2'-deoxyuridine using n-butyllithium followed by boronation at -65 deg C with tri-n-butyl borate in the presence of HMPT.After hydrolysis, the product was purified by column chromatography and repeated fractional crystallization and the purity determined by HPLC.This hydrolytically stable compound showed no activity against Sarcoma 180 (S-180) but inhibited herpes simplex virus type 1 at a nontoxic concentration.The compound sensitized hamster V-79 cells to neutrons and could be of potential use in boron neutron capture therapy. 5-(Dihydroxyboryl)uracil and 6-(dihydroxyboryl)uracil were prepared also by a similar route from the corresponding 5- or 6-bromo-2,4-bis(benzyloxy)pyrimidine.However, the mixture was maintained at -85 deg C during the whole reaction sequence and the product was obtained by hydrolysis followed by catalytic hydrogenation.The physical characteristics of these analogues, as well as those of their iminodiethanol esters, are described.