Studies on antitumor agents. IV. Syntheses and antitumor activities of compounds related to 1-(tetrahydro-2-furanyl)-5-fluorouracil metabolites.

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Abstract
A hydroxylated metabolite of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT), 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (trans-3''-OH-FT, VIII) and its isomer, 1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (cis-3''-OH-FT, VI), were synthesized and isolated at high purity. As compounds related to FT metabolites, 2,3''-anhydro-1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (2,3''-anhydro-FT, V), 1-(2,5-dihydro-2-furanyl)-5-fluorouracil (3'',4''-dehydro-FT, XII) and 1-(5-acetoxytetrahydro-2-furanyl)-5-fluorouracil (5''-AcO-FT, XI) were also synthesized. The antitumor activities of these compounds against (mouse) sarcoma 180 and (leukemia) L 1210 were examined. The activities of cis-3''-OH-FT (VI) and 2,3''-anhydro-FT (V) were lower than that of FT. The activity of 5''-AcO-FT (XI) was the same as that of FT. 3'',4''-Dehydro-FT (XII) showed much greater activity than FT.