Thio-sugar Nucleosides

Reist, E J, Eisher, L V, Goodman, L, Thio Sugars. Synthesis of the adenine nucleosides of 4-thio-D-xylose and 4-thio-D-arabinose, J. Org. Chem., 33, 189-192, 1968. 

The yeast nucleoside containing a thio sugar has been shown to be 6-amino-9-(5-d-methyl-5-thio-D-ribofuranosyl)-9i/-purine []5-deoxy-5-(methyIthio)adenosine] (130). 

Natural products still have many surprises in store, as evidenced by the discovery of the antibiotic oxetanocin, a nucleoside analogue possessing a four-membered sugar ring other antibiotics apparently contain novel thio-sugar components. We have reviewed about 1460 references for this report. 

The synthesis of purine and pyrimidine 2 -deoxynucleosides from a 1,2-dithio-sugar precursor is noted in Chapter 21, which also refers to the alkylation of seleno- and thio-substituted nucleosides using a mixture of a dialkyl disulphide (or diselenide) and tributylphosphine in DMF. Other thio-sugar derivatives are mentioned in Chapter 12. 

Significant stability of ketohexose nucleosides in various media has facilitated their direct transformation, leading to important structures of biological interest, such as branched-chain and rare-sugar nucleosides (for example, amino-, epimino-, thio-, and trideoxy-nucleosides). 

This article collates information on the reactivity of sugar isothiocyanates and isomeric thiocyanates, and illustrates some of the chemical properties that have contributed to the synthesis of nucleoside analogs,1719 and thio and deoxy sugars. 

In an article that collates information not extensively treated before, Z. J. Witczak (West Lafayette) describes the synthesis, chemistry, and preparative applications of monosaccharide thiocyanates and isothiocyanates the thiocyanate anion is an ambident nucleophile of great synthetic versatility in approaches to nucleoside analogs and to thio and deoxy sugars. 

Structures of a range of base and/or sugar-modified nucleoside analogues have been described. The 6-azacytosine 71, pyrazolo[3,4-/>]quinoline P-ribo-furanoside 72 5 -0-benzoyl-3 -deoxy-2 -keto-a-uridine, 3 -deoxy-3 -5-(2-nitrophenyldisulfanyl)thymidine, ° anhydronucleoside 73, 5-adamantyl-2 -deoxy-4 -thio-a-uridine, the bicyclic nucleoside analogue 74, and bicyclic analogues 75 (both epimers) and 76. ... 

The oxadiazole 140, related to ribavirin, has been prepared by cyclization of a known sugar-protected amidoxime. The 4 -thio-analogues 141 (X = O, S) of furanfurin and thiophenfurin (Vol. 29, p. 283), themselves analogues of ribavirin, have been prepared by condensation between the heterocycles, as their ethyl esters, with 0-protected derivatives of 4 -thioribofuranosyl acetate. The thiophene compound ( thiophenthiofurin ) had cytotoxicity towards cancer cell lines, but less so than thiophenfurin. A previously-known 2,5-anhydroglucose derivative 142 has been converted to the pyrazole 143, and some related compounds. Some pyrazole iso-C-nucleosides are mentioned in Chapter 2. Various 3-cyano-2-(P-D-ribofuranosyl)-1,5-benzodiazepines have been prepared by a novel ring transformation of 5-(tri-0-benzoyl-p-D-ribofuranosyl)isoxazole-4-carbaldehyde. ... 

Both ribose-l-P and deoxyribose-l-P serve as sugar donors in the synthetic reaction. In addition to the naturally occurring purines, certain purine analogues can also serve as substrates or inhibitors of purine nucleoside phosphoiylase. Of these, 8-azaguanine, 6-mercaptopurine, 6-thio-guanine, and allopurinol bind most tightly to the human erythrocyte enzyme 17). 

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