Uridine 2,2 -anhydro

It is claimed that this reaction proceeds via a 2, 3 -thionocarbonate or a thiocarbamate derivative. If the 5 -OH group of uridine was not protected, the yield of the 2,2 -anhydro-l-(j -D-arabinofuranosyl)uracil was low. 

Another example of displacement at C2 with fission of the anhydro bridge has been observed263 in the hydrolysis of the 3,5-diacetate ester of LXXXVII with dilute mineral acid. Aside from the expected spongouridine (XXXIII, R = H), uridine was obtained in appreciable yield. The production of uridine finds a ready explanation in the formation, in part, of an intermediate orthoester ion during the reaction, as a result of a nucleophilic... 

The studies of Levene and LaForge60 on the nitration of uridine have since been re-investigated. It had been reported, several decades ago, that treatment of uridine with nitric acid produced a Nitro-Uridin-Carbon-saure which was stated to be a dimer containing an anhydro typeof linkage (positions unspecified) between two nucleoside residues.60 According to an abstract,269 this compound has now been identified as the monomeric 5-ni-tro-l-(/8-D-ribosyluronic acid)uracil (CXXII) this was converted to the isopropyl ester and the 2,3-O-isopropylidene acetal thereof. Nitration of the pyrimidine moiety of uridine without oxidation of the 4-(hydroxy-... 

Uridine 3 -phosphate (147) was prepared by Hall and Thedford by the phosphorylation of 2, 5 -di-0-trityluridine with 2-cyanoethyl phosphate and iVjiV -dicyclohexylcarbodiiinide to give the diester (146). This diester was de-esterified with alkali, and then hydrolyzed with 80% acetic acid at 100° for 90 minutes, to give (147). The structure of (14S) had been rigorously established by Yung and Fox, who methanesulfonated (145) to obtain (148). Treatment of (148) with sodium benzoate in N,N-di-methylformamide gave the 2,3 -anhydronucleoside (149). The anhydro... 

Indeed, in the acid hydrolysis of uridine 3 5 -cyclic phosphate (175), reported by Khorana and coworkers, the 67% yield of uracil observed may represent the minimum amount of anhydronucleotide intermediates (176) and (180) which had formed, as uridine 5 -phosphate is, under these conditions, completely stable. In addition to cleavage to uracil, it would be expected that some of the anhydronucleotide (180) would also give rise to uridine 3 (2 )-phosphate. Furthermore, intermediate (176) may also generate l- 3-D-xylofuranosyluracil 5 -phosphate (177) and its arabino isomer (181), as well as uracil. Such a reaction has been observed by Yung and Fox in the acid hydrolysis of 2,3 -anhydro-l- 3-D-xylofuranosyl-uracil (182), which yielded the xylo- (183) and arabwo-nucleosides (184) and uracil. The formation of the arabino nucleoside (184) would arise by conversion of some of (182) into a 2, 3 -epoxide, which would be directly hydrolyzed to (183) and (184), or by conversion of this 2, 3 -epoxide into a 2,2 -anhydronucleoside, which would be hydrolyzed by acid to (184). Such mechanisms, applied to the anhydronucleotide (176), could give rise to (177) and (181). 

Sodium ferf-butoxide in N,N-dimethylformamide at KXP was found to be very effective in promoting intramolecular displacements408 and 2,5 -anhydrothymidine was obtained directly from 5 -0-(methyl-sulfonyl)thymidine with these reagents. The same conditions have also been used to synthesize the anhydronucleosides 121 and 122 from a pseudouridine derivative408 and from a D-ribosyl derivative of 2,4-quinazolinedione.410 The same reagents with 3 -0-p-tolylsulfonyl-uridine gave mainly 1 -(2,3 -anhydro-y3-D-xylofuranosyl)uracil.408... 

Treatment of 2, 3, 5 -tri-0-(methylsulfonyl)uridine (137) with one equivalent of sodium hydroxide in aqueous ethanol gave high yields of the 2-2 -anhydride (138), demonstrating the favored formation of the cis-fiised, five-membered ring-system.417 When aqueous solutions of 138 or of the corresponding 5 -0-benzoyl (139) or 5 -deoxy (140) derivatives were boiled for one hour, good yields of the D-lyxo-furanosyluracil derivatives 141, 142, and 143 were obtained.418 The mechanism of this reaction involves initial hydrolysis of the 2,2 -anhydro bond, intramolecular displacement at C-3, and, probably, rearrangement to the 2,2 -anhydride prior to hydrolysis.3 ... 

J.-C. Wu and J. Chattopadhyaya, Michael addition reactions of a,P-ene-3 -phenylselenone of uridine. New synthesis of 2, 3 -dideoxy-riZ)o-aziridino-, 2, 3 -dideoxy-2, 3 -r feo-cyclopropyl-, and 2,2 -0-anhydro-3 -deoxy-3 -aminouridine derivatives, Tetrahedron, 45 (1989) 4507-4522. 

Compounds of the type 65 have been prepared by opening of the epoxide ring of l-(2,3-anhydro-5-0-trityl-P-D-lyxofuranosyl)uracil with a variety of carbon nucleophiles such as ethynyl lithium, vinylmagnesium bromide/cuprous iodide and l,3-dithian-2-yl lithium. These reactions afforded regioselectively 3 -C-substituted-3 -deoxy-P-D-arabinofuranosyl nucleosides 69-71 in 10-68% yield [84, 87] (Fig. 12). These intermediates have been transformed into a variety of other 3 -C-substituted-3 -deoxy-arabinofuranosyl uridines 72-77 [84]. 9-(3-Deoxy-3-C-methyl-P-D-xylofuranosyl)adenine has been prepared by glycosidation reaction of a 3-deoxy-3-C-methyl-P-D-xy/ofuranosyl chloride with adenine [90]. 

Anhydro-adenosine has been isomerized to 2, 3-anhydro-jS-D-lyxo-furanosyl-adenine in 42% overall yield by the sequence outlined in Scheme 8. Deamination of l-(3-amino-3-deoxy-j3-D-xylofuranosyl)-uracil with nitrous acid did not yield any 2, 3 -anhydro-uridine or products derived from this anhydro-sugar derivative, uracil being the major product. ... 

Benzoylation. Triethylamine added to a stirred mixture of b-ethyl-O. /. nhydro-uridine, benzoyl cyanide, and acetonitrile, and stirred 1 hr. at room temp. -> 3, 5 -di-0-benzoyl-02,2 -anhydro-6-ethyluridine. Y 78%. F. e. s. A. Holy, Coll. 39, 3374... 

Br]-2 -Bromo-2-deoxy-uridine has been prepared either from 2,2 -anhydro-uridine using radio labelled ammonium bromide or by irradiation of unlabelled... 

Nucleosides, Nucleotides, Derivatives, and Related Compounds. — 5-Substituted uracils were examined for conformational dependence on the substituents, uridine 5 -phosphate disodium salt, 2 -deoxyuridine 5 -phosphate disodium salt, " 6-methyl-2 -deoxyuridine, 5-C-acetyl-2 -deoxyuridine, dihydrouridine 3 -phosphate potassium salt, 5-hydroxymethyl-2 -deoxyuridine, 4-thio--uridine, 2,5 -anhydro-2, 3 -0-isopropylidene-2-thiouracil, 2,2 -an-hydro-1 - 3-D-arabinofuranosyl-2-thiouracil. ... 

Syntheses of3,6-anhydro-l-deoxy-l-(5-halogenouracil-l-yl)-D-mannitols and 5-cyclopropyl-uridine and -6-azauridine ° have been described. Carbenes added to the 5,6-double bond of uridine derivatives to give a mixture of endo- and exoadducts [ e.g. (552)] in modest to good yields. The adducts (552) or those obtained... 

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