Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers.
1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D005472:Fluorouracil / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000503:physiopathology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005641:Tegafur / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
D005641:Tegafur; D005472:Fluorouracil