55474-11-8

Basic information

• Product Name: 5-fluoro-1-(2,3,5-tri-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione
• Synonyms: 4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl)tetrahydro-3-furanyl acetate
• CAS NO: 55474-11-8
• Molecular Formula: C₁₅H₁₇FN₂O₉
• Molecular Weight: 388.3019
• Mol File: 55474-11-8.mol

Chemical Properties

• Density: 1.48g/cm³
• Refractive Index: 1.539
• CAS DataBase Reference: 5-fluoro-1-(2,3,5-tri-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 5-fluoro-1-(2,3,5-tri-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione(55474-11-8)
• EPA Substance Registry System: 5-fluoro-1-(2,3,5-tri-O-acetylpentofuranosyl)pyrimidine-2,4(1H,3H)-dione(55474-11-8)

Safety Data

• Hazardous Substances Data: 55474-11-8(Hazardous Substances Data)

Upstream product

• 316-46-1 5-fluorouridine 
• 108-24-7 acetic anhydride 
• 4105-38-8 Tri-O-acetyluridine 
• 51-21-8 5-fluorouracil 
• 13035-61-5 1,2,3,5-tetraacetylribose 
• 40554-98-1 [(2R,3R,4R)-3,4-diacetoxy-5-chlorotetrahydrofuran-2-yl]methyl acetate 
• 17242-85-2 5-fluoro-2,4-bis(trimethylsilyloxy)pyrimidine 
• 28708-32-9 1,2,3,5-tetra-O-acetyl-D-ribofuranose 
• 194474-73-2 2′,3′,5′-tri-O-acetyl-5-nitrouridine 
• 105659-31-2 5-bromo-2’,3’,5’-tri-O-acetyluridine 
• 4105-38-8 2',3',5'-tri-O-acetyl-uridine 

Downstream Products

• 2341-22-2 5-fluorocytidine 
• 175650-97-2 5'-O-dimethoxytrityl-4-O-methyl-5-fluorouridine 
• 175650-98-3 1-[(2R,3R,4R,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-3-(tert-butyl-dimethyl-silanyloxy)-4-hydroxy-tetrahydro-furan-2-yl]-5-fluoro-4-methoxy-1H-pyrimidin-2-one 
• 1338923-32-2 5'-O-(4,4'-dimethoxytrityl)-4-deoxo-3,4-dehydro-4-(2-cyanoethylthio-)-5-fluorouridine 
• 1338923-34-4 5'-O-(4,4'-dimethoxytrityl)-2'-O-methyl-4-deoxo-3,4-dehydro-4-(2-cyanoethylthio)-5-fluorouridine 
• 1338923-35-5 5'-O-(4,4'-dimethoxytrityl)-3'-O-methyl-4-deoxo-3,4-dehydro-4-(2-cyanoethylthio)-5-fluorouridine 
• 316-46-1 5-fluorouridine 
• 727-79-7 5-fluoro-4-thiouridine 
• 316-46-1 5-fluorouridine 

Relevant articles and documents

Transglycosylation in the Modification and Isotope Labeling of Pyrimidine Nucleosides

Transglycosylation of pyrimidine nucleosides is demonstrated in a one-pot synthesis of uridine derivatives under microwave irradiation. Inductive activation of 2′,3′,5′-tri-O-acetyl uridine with a 5-nitro group produces a more-reactive glycosyl donor. Under optimized Vorbrüggen conditions, the 5-nitrouridine facilitates a reversible nucleobase exchange with a series of 5-substituted uracils. The protocol is also exemplified in a gram-scale reaction under thermal heating. The strategy provides easy access to isotopically labeled uridine.

A solid-supported acidic oxazolium perchlorate as an easy-handling catalyst for the synthesis of modified pyrimidine nucleosides via Vorbrüggen-type N-glycosylation

A solid-supported acidic oxazolium perchlorate was investigated as a heterogeneous catalyst in N-glycosylation reactions using silylated modified pyrimidines and an acylated ribose or glucose to afford the corresponding pyrimidine nucleosides. This salt is a nonhygroscopic and stable powder whose activity is comparable to that of 2-methyl-5-phenylbenzoxazolium perchlorate. A reaction with this polymer catalyst can be conducted on a gram scale. Reusability of the solid-supported catalyst was also investigated.

Effective synthesis of nucleosides utilizing O-acetyl-glycosyl chlorides as glycosyl donors in the absence of catalyst: Mechanism revision and application to silyl-hilbert-johnson reaction

An effective synthesis of nucleosides using glycosyl chlorides as glycosyl donors in the absence of Lewis acid has been developed. Glycosyl chlorides have been shown to be pivotal intermediates in the classical silyl-Hilbert-Johnson reaction. A possible mechanism that differs from the currently accepted mechanism advanced by Vorbrueggen has been proposed and verified by experiments. In practice, this catalyst-free method provides easy access to Capecitabine in high yield.

Systematic assignment of NMR spectra of 5-substituted-4-thiopyrimidine nucleosides

Unambiguous characterization of 5-substituted-4-thiopyrimidine nucleosides (ribonucleosides and 2'-deoxynucleosides) was performed using NMR spectroscopy. Assignments of all proton and carbon signals of 5-bromo-4-thiouridine and related nucleosides were systematically carried out and firmly established by COSY and HMQC techniques. The NMR data of various 4-thiopyrimidine nucleosides are compared, and the key contributing factors discussed. The approach presented here is applicable to other modified nucleosides and nucleotides, as well as nucleobases. Copyright

Triazole pyrimidine nucleosides as inhibitors of Ribonuclease A. Synthesis, biochemical, and structural evaluation

Five ribofuranosyl pyrimidine nucleosides and their corresponding 1,2,3-triazole derivatives have been synthesized and characterized. Their inhibitory action to Ribonuclease A has been studied by biochemical analysis and X-ray crystallography. These compounds are potent competitive inhibitors of RNase A with low μM inhibition constant (Ki) values with the ones having a triazolo linker being more potent than the ones without. The most potent of these is 1-[(β-d-ribofuranosyl)-1,2,3-triazol-4-yl]uracil being with Ki = 1.6 μM. The high resolution X-ray crystal structures of the RNase A in complex with three most potent inhibitors of these inhibitors have shown that they bind at the enzyme catalytic cleft with the pyrimidine nucleobase at the B1 subsite while the triazole moiety binds at the main subsite P1, where P-O5′ bond cleavage occurs, and the ribose at the interface between subsites P1 and P0 exploiting interactions with residues from both subsites. The effect of a susbsituent group at the 5-pyrimidine position at the inhibitory potency has been also examined and results show that any addition at this position leads to a less efficient inhibitor. Comparative structural analysis of these RNase A complexes with other similar RNase A - ligand complexes reveals that the triazole moiety interactions with the protein form the structural basis of their increased potency. The insertion of a triazole linker between the pyrimidine base and the ribose forms the starting point for further improvement of these inhibitors in the quest for potent ribonucleolytic inhibitors with pharmaceutical potential.

Functionalization including fluorination of nitrogen-containing compounds using electrochemical oxidation

Nitrogen-containing compounds have been subjected to electrochemical oxidation with Et3N-3HF as an electrolyte. Caffeine afforded 8- fluorocaffeine as a sole product in 40.3% yield. Guanosine tetraacetate and uridine triacetate gave the fluorinated compounds in 17.5 and 4.6% yields, respectively. Similar electrochemical oxidation of caffeine with methanol, KCl, or KCN afforded 8-methoxycaffeine, 8-chlorocaffeine, or 8- cyanocaffeine, respectively.

A convenient synthesis of 5-fluoropyrimidines using 1-(chloromethyl)-4-fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate)-SELECTFLUOR reagent

The pyrimidine bases uracil and thymine react with the titled reagent in water to generate the corresponding fluorohydrins. Uracil fluorohydrin provides 5-fluorouracil on sublimation. Triacetyluridine reacts similarly in the presence of H2O, AcOH, or MeOH to form the respective adducts from which 5-fluorotriacetyluridine was obtained. The fluorohydrin of diacetylthymidine and the difluoromethoxy derivative of triacetylcytidine were also obtained by reaction of the nucleosides with 1-(chloromethyl)-4-fluoro-1,4-diazobicyclo[2.2.2]octane bis(tetrafluoroborate)-SELECTFLUOR in H3O and MeOH, respectively. This method represents a new practical and direct route to 5-fluoropyrimidine nucleoside.

The synthesis of difluoro and trifluoro analogues of pyrimidine deoxyribonucleosides: a novel approach using elemental fluorine

The preparation of some novel fluorodeoxy nucleosides in good yields by the fluorination of unsaturated intact nucleosides with elemental fluorine at -78 deg C in mixtures of chloroform, ethanol and fluorotrichloromethane is described.This is the first example of the fluorination of an intact nucleoside by elemental fluorine and represents a considerable step forward in the use of the element in the synthesis of bioactive species.Thus, we were able to obtain 1-(2',3'-didehydro-2',3'-dideoxy-β-D-ribofuranosyl)-5-fluorouracil (6), 1-(2',3'-didehydro-2',3'-dideoxy-2',3'-difluoro-β-D-ribofuranosyl)-5-fluorouracil (7), 1-(2',3'-didehydro-2',3'-dideoxy-2-fluoro-β-D-ribofuranosyl)-5-fluorouracil (8), 1-(2',3'-dideoxy-2',3'-difluoro-β-D-ribofuranosyl)-5-fluorocytosine (10), 2',3'-dideoxy-5-fluorouridine (11), 1-(2',3'-dideoxy-2'-fluoro-β-D-arabinofuranosyl)-5-fluorouracil (12), 1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-5-fluorouracil (13), 1-(2-deoxy-3,5-di-O-acetyl-β-D-ribofuranosyl)-5-fluorouracil (14) and (5R,6S)- and (5S,6R)-1-(3',5'-anhydro-2-deoxy-β-D-threo-pentofuranosyl)-difluoro-5,6-dihydro-5-methyluracil (16 and 17) by a series of fluorinations and deprotections.From the products we have obtained, it is clear that (at least in these fluorinations) the addition of the fluorine is in a cis mode.

Functionalization Including Fluorination of Caffeine, Guanosine Tetraacetate, and Uridine Triacetate using Electrochemical Oxidation

The title compounds have been subjected to electrochemical oxidation with Et3N-3HF as an electrolyte.Caffeine afforded 8-fluorocaffeine as a sole product in 43percent yield.Guanosine tetraacetate and uridine triacetate gave the fluorinated compounds in 7.3 and 4.8 percent yield, respectively.Similar electrochemical oxidation of caffeine with methanol, KCl or KCN yielded 8-methoxycaffeine, 8-chlorocaffeine, or 8-cyanocaffeine, respecticvely.

NMR studies show monomeric 5-fluorouridine forms base pairs of increased stability compared with uridine in non-aqueous solvents

The binding constants and geometries for nucleoside base pairs involving 5-fluorouridine (FUr) and adenosine were determined by 1H, 13C, and 19F NMR to better understand how FUr may perturb RNA structure. 5FU:A base pairs are more stable than U:A base pairs.