Abstract
Several 5-fluorouracil derivatives in which the phthalidyl (1, 3-dihydro-3-oxoisobenzofuran-1-yl) group, appropriately substituted on its benzene ring, is substituted at the N (1)-or N (3)-position or at both positions were synthesized, and their antitumor activities were evaluated. Among these compounds, 1-(1, 3-dihydro-3-oxoisobenzofuran-1-yl)-5-fluorouracil (3a, 590-S) was shown to be markedly active against several experimental tumor systems. Several methods for a simple and efficient large-scale preparation of 3a were examined. The large-scale preparation of 3a was effected most efficiently by the condensation of 5-fluorouracil with the quaternary ammonium salt of 3-bromophthalide in the presence of a base. The synthesis of (+)- and (-)-3a is also described.
