861. Deoxynucleosides and related compounds. Part VIII. Some further transformations of O²: 2′-cyclouridine

Abstract

Heating 5'-O-acetyl-2'-O-toluene-~-sulphonyluridine (I) with either sodium azide in methyl cyanide or sodium acetate in acetonylacetone affords 5'-0-acetyl-02 : 2'-cyclouridine (11; R = H, R' = Ac). The latter is converted into 5'-O-acetyl-2'-deoxy-2'-iodouridine (111) by sodium iodide in acetonylacetone containing glacial acetic acid ; the iodide (111) , also obtained directly from sulphonyl derivative (I) with sodium iodide, is now assigned the ribo-configuration.3' : 5'-Di-O-acetyl-0 : 2'-cycZouridine on acid hydrolysis gives both uridine and spongouridine, in contrast to O2 : 2'-cycZouridine which gives only the latter. The chemistry of the oxazolidine ring in cyclouridine derivatives is discussed and a possible pathway is suggested for the biochemical conversion of pyrimidine ribo-into deoxyribo-nucleosides.

Chemistry of the Nucleotides

“…Thus,S' -0-acetyl-2-0-toluene p-sulphonyl uridine on reaction with sodium iodide gave S'-O-acetyl-2' deoxy-2'-iodouridine, from which 2'-deoxyuridine was obtained by reduc tion and deacetylation (37). Since the same iodo derivative was obtained by the action of sodium iodide and acetic acid on 5'-O-acetyl-02,2'-cyclouridine (to which it could be reconverted by treatment with base), Brown, Parihar & Todd (38) consider the cyclonucleoside to be an intermediate in the re placement of the toluene-p-sulphonyl group by iodination, the final product being the result of two displacements with inversion at 0'. The same proce dures applied to 5'-O-acetyl-3-,B-D-ribofuranosyl thymine yielded thymidine (37).…”

The Reaction of O-Benzylidene Sugars with N-Bromosuccinimide.: VI. A New Synthesis of 2′-Deoxyuridine and some of its Selectively Substituted Derivatives

“…Conventional 2'-Deoxyuridine (5) 3'-0-Benzoyl-2'-deoxyuridine (100 mg) was dissolved in anhydrous methanolic ammonia (7 ml) and the solution was allowed to stand in the cold overnight. Evaporation to dryness below 20" (bath temperature) followed by addition of methanol and repeated evaporation afforded a syrup.…”

“…The introduction of a halogen atom in the 5-position of the uracil ring, imparts biologically and therapeutically significant properties to the parent nucleoside, as in the case of 2'-deoxy-5-halouridines (4). Of the procedures available for the synthesis of 2'-deoxyuridine, those based on nucleoside interconversion, resulting in the ultimate placement at C-2' of a reducible function such as halogen (5)(6)(7)(8)(9)(10) or thioether (11) groups, are among the 'For part V, see ref.…”

Synthesis of some pyrimidine 2'-amino-2'-deoxynucleosides

“…The dichloroacetyl derivative of the 2'-amino group was prepared by conventional methods. Acetylation of 3 followed by reaction with phosphorus pentasulfide and amination of the resulting 4-thiouracil derivative gave 2'-amino-2'-deoxycytidine (8). The latter compound was also obtained directly by reaction of 3',5'-di-0-acetyl-2'-azido-2'-deoxyuridine (9) with phosphorus pentasulfide in pyridine followed by treatment with methanolic ammonia.…”

“…The methods of synthesis have involved both transformations of preformed nucleosides2•513'6'7 and condensations of derivatives of suitable amino sugars with the purine or pyrimidine bases. The notably missing member in the above series is the pyrimidine 2 '-amino-2 '-deoxyribonucleosides and in this paper we describe the synthesis of two such compounds, namely l-(2-amino-2-deoxy-d-D-ribofuranosyl)uracil (3) and l-(2-amino-2-deoxy-/3-D-ribofuranosyl)cytosine (8).…”