2 -Deoxy-2 -fluorouridine synthesis

C.Y. Shiue, A.P. Wolf, M. Friedkin, Synthesis of 5 -deoxy-5-[ F]-fluorouridine as a probe for measuring tissue proliferation in vivo, J. Label. Compds Radiopharm. 19(1982) 1395. 

Analogous reactions have been carried out with uridine (CXI, b series) and with l-jS-D-ribofuranosylthymine (CXI, c series).62 The latter series provided an avenue to the synthesis of 5 -methylcytidine, a nucleoside which is probably identical with that detected by Dunn60 in the ribonucleic acid of wheat germ. The thiation process has also been applied to the synthesis of 5 -fluorocytidine and 2-deoxy-5 -fluorocytidine261 from 5 -fluoro-uridine and 2-deoxy-5 -fluorouridine,209,228 respectively.2618... 

Uridine and A -benzyluridine have been reported to show sleep-promoting activity [37] and hypnotic activity [38], respectively. We have been very interested in this topic and have studied the hypnotic activity of A3-substituted 2 -deoxy-2 -a-fluorouridines to determine their SAR trends. For the synthesis of the key compound 4 (2 -deoxy-2 -a-fluorou-ridine), an alternative synthetic route via arabinoside was developed since a previously reported method [39] involving a ring-cleavage reaction of 2,2 -O-cyclouridine (3, X = H) required severe reaction conditions, such as exposure to HF (see Scheme 7.1). The new route is illustrated in Scheme 7.7. The hydroxyl groups of 2,2 -O-cyclouridine (3) were... 

Sato, Y., Utsumi, K., Maruyama, T., et al. (1994) Synthesis and hypnotic and anti-human immunodeficiency virus-1 activities of -Substituted 2 -Deoxy-2 -fluorouridines. Chem. Pharm. Bull., 42, 595-598. 

Different synthetic routes have been described for synthesis of 2 -modified nucleosides [152]. 2 -Fluoro nucleosides are usually prepared starting from arabinofuranosylnucleosides. 2,2 -Anhydroarabinofuranosyluracil 61 has been reported to yield 2 -deoxy-2 fluorouridine upon treatment with hydrogen fluoride. 2 -Amino-2-deoxyuridine may be easily prepared by similar rearrangements in large scale synthesis [153]. Synthesis of 2 -deoxy-2 -fluoropurine... 

An enzymic synthesis of 2 -deoxy-2 -fluororibavirin (63) has been reported, involving the use of nucleoside transferase to exchange the triazole of ribavirin with the base of 2 -deoxy-2 -fluorouridine. ... 

Farquhar D, Khan S, Srivastva DN, Saunders PP (1994) Synthesis and antitumor evaluation of bis[(pivaloyloxy)methyl] 2 -deoxy-5-fluorouridine 5 -monophosphate (FdUMP) a strategy to introduce nucleotides into cells. J Med Chem 37 3902-3909... 

This approach has been applied to the delivery of the 5 -monophosphate of anticancer nucleoside, 2 -deoxy-5-fluorouridine (FdU) [78, 79], in which prodrug (59, R = 5 -FdU) cleaves to FdU 5 -monophosphate and acrolein in the presence of carboxyesterase. The prodrug inhibited DNA synthesis in both Chinese hamster ovary cells and thymidine kinase-deficient mouse fibroblasts this effect has been attributed to intracellular metabolism to FdU 5 -monophosphate and subsequent inhibition of thymidine monophosphate synthase. The prodrug was also as effective as 5-ffuorouracil in prolonging the life-span of mice with P-388 leukaemia. The prodrug was tolerated better by mice when administered with 2-mercaptoethanesulphonic acid, a scavenger for the toxic by-product, acrolein. 

Deoxy-3 -fluorouridine has been synthesized in four steps from 5-O-benzyl-3-deoxy-3-fluoro-D-arabinofuranose, but it did not inhibit RNA synthesis in vitrol-(6-Deoxy-6-fluoro- -D-glucopyranosyl)thymine has been prepared by a direct displacement on a corresponding nucleoside 6 -sulphonate with fluoride ion, whereas l-(6-deoxy-6-fluoro-j3-D-gaIactopyranosyl)thymine was obtained via condensation of l,2,3,4-tetra-0-acetyl-6-deoxy-6-fluoro-/3-D-galactopyranose with 5-methyl-2,4-bis(trimethylsilyioxy)pyrimidine. ... 

Hfebabecky H, Beranek J (1978) 5 -halogeno-2, 3 -cyclic sulphite isomers in the preparation of 5 -halogeno nucleosides. Synthesis of 5 -deoxyuridine and 5 -deoxy-5-fluorouridine. Nucleic Acids Res 5 1029-1040... 

The synthesis of a series of 2 -fluoro-5-substituted arabinofuran-osyl-cytosines and -uracils has been described. 5-Methyluracil and 5-iodocytosine derivatives were the most effective against herpes simplex virus. The arabino configuration was essential for antibiotic activity, and corresponding chloro and bromo analogues were less effective.5 -Bromo-, 5 -fluoro-, and 5 -iodo-deriv-atives of 5-fluorouracil have been prepared conventionally. The a-anomer of 5 -fluoro-5 -deoxyuridine has been synthesized from a 1,2-oxazoline derivative of 5-deoxy-5-fluoro-D-ribose, in turn prepared by a sulphonate displacement using pyridinium fluoride. Treatment of 1-(o-D-arabinofuranosyl)-uracil with diphenylcarbonate yielded the 1,4-oxazin derivative (23) which yielded the 2 -chloro-2 -deoxy-arabino-a-nucleoside (24) on chlorination this was then reduced to the 2 -deoxy analogue (25). 5-Fluorouridine has been... 

MJ. Robins, K.B. Mullah, S.F. Wnuk, and N.K. Dailey, Nucleic acid related compounds. 73. Fluorination of uridine 2 -thiocthers with xenon difluoride or (diethylamino)sulfur trifluoride. Synthesis of stable 2 -[alkyl(or aryl)sulfonyl]-2 -deoxy-2 -fluorouridines,/. Org, Chem, 57 2357 (1992). 

An improved synthesis of 2 -deoxy-2 -fluoroadenosine has been described, involving a sequence of two inversions of configuratkMi at C-2 of an adenosine derivative, whilst the 2 -deoxy-2 -fluoroderivatives of a wide range of purine nucleosides have been made by glycosyl transfn 6tMn 2 -deoxy-2 -fluorouridine uring diymidine phosphorylase and purine nucleoside phosphc lase. ... 

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