Tegafur derivatives

M-Benzyl-O-methyl-L-serinoate (173) was condensed with phosphoryl trichloride giving cyclic chloridate 174 that reacted with the Tegafur derivative 175 with the formation of almost equal amounts of 2-alkoxy-l,3,2 oxazaphospholidine-2-oxides 176a and 176b (Scheme 49) [80],... 

The pyrimidine 5-fluorouracil (64) is used extensively in the clinic as an antimetabolite antitumor agent. As a consequence of poor absorption by the oral route, the drug is usually administered by the intravenous route. A rather simple latent ated derivative, tegafur (66), has overcome this limitation by providing good oral absorption. Reaction of 5-fluorouracil with trimethylsilyl chloride in the presence of base gives the disilylated derivative (65). Reaction of this with dihydrofuran (obtained by dehydro-... 

Fluorouracil and its derivatives are still important dmgs in the chemotherapy of numerous cancers (doxifluridine, tegafur, carmofur) (cf. Chapter 8). Studies on the mechanism of action of 5-FU had great influence on the development of other antitumor drugs that are derived from pyrimidine and purine. 5-FU is industrially prepared by fluorination of uracil with elemental fluorine (cf. Figure 2.6, Chapter 2). 

Pyrimidine derivatives capecitabine, cytarabine, fluorouracil (SEDA-23,476), gemcitabine, tegafur. 

Syntheses of Fluorouracil prodrugs relied on either chemical modification of 1 or direct fluorination of the corresponding pyrimidine derivatives. In particular, Tegafur (3) was obtained from 1 by reaction with 2,3-dihydrofuran [49-54], 2-chloro- [55, 56], 2-alkoxy- [57], 2-acetoxytetrahydrofuran [58, 59, 300], and 4-tri-methylsilyloxybutyraldehyde dimethyl acetal (48) (Scheme 9) [60]. Alternatively, 3 was prepared via fluorination of compound 49 [61] or ester 50 [62],... 

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