5 -Ketonucleosides, synthesis

Stereoselective synthesis of 3 -substituted 2 -deoxy C-nucleoside pyrazolo[l,5- ][l,3,5]triazines and their 5 -phos-phate nucleotides starting from related 3 -ketonucleosides have been accomplished <2006TL5099>. Regioselective ring closure to derivatives of the same ring system - reminiscent of those discussed in Section 11.17.5.3.5 - has been described <2006TL5441>. 

This Subsection deals with the preparation of 2 - and 4 -ketohexosyl-purines and -pyrimidines, which have proved to be versatile synthetic intermediates. A 5 -keto derivative of a hexofuranose nucleoside is also described. The synthesis of epoxy-, halogeno-, unsaturated, epimino-, and thio-ketonucleosides will be developed in subsequent Subsections and Sections. 

The synthesis of the first reported51,52 unsaturated ketonucleoside, 61a, was accomplished by acetylation of the known 7-(6-deoxy-/ -L-h/xo-... 

Among the unsaturated ketonucleosides may be classified the disaccharide derivative 74, which is an analog of the biologically active compound 68c. The key intermediate for the synthesis of this unsaturated ketodisaccharide nucleoside was the partially protected, disaccharide nucleoside 73, which was prepared by two separate routes,56 Treatment of 73 with the Me2SO-acetic anhydride reagent for two days at room temperature afforded 7-[2,3-di-0-benzoyl-4-0-(3-0-benzoyl-2,6-di-deoxy - / - d - glycero - hex - 2 - enopyranosyl - 4 - ulose) - 6 - deoxy - / - d -glycopyranosyl]theophylline (74), isolated crystalline.56... 

The role of the reaction medium for the successful synthesis and study of the reactions of ketonucleosides has also been emphasized by Hersco-vici and Antonakis, who reported40,41 catalytic solutions to this problem. Thus, the use of inorganic catalysts proved to be of great efficiency for the oxidation of fragile molecules, especially in the nucleoside field. 

Other pyrimidine keto-nucleosides, such as 47a and 47b, could be treated with acetic anhydride-pyridine without glycosylic cleavage.33 The stability of 47a and 47b in this medium permitted elaboration of a new, mild, regioselective synthesis of enol acetates, The reaction of 4 -ketonucleosides of uracil with acetals of N,N-dimethylformamide led,33 after addition of acetic anhydride, to the corresponding enol acetate-nucleosides 77a and 77b. 

In contrast to nucleophilic additions to ketoses, which very often lead to diastereoisomeric products, additions to ketonucleosides have been found to be highly stereoselective, permitting ready synthesis of amino-, epimino-, triazolo-, and other rare-sugar nucleosides. 

Nevertheless, the availability of ketonucleosides due to the methods of synthesis described in Section II has, over the past decade, produced some interesting biological studies opening large horizons for extensive... 

A thorough investigation12 of the effects of the unsaturated ketonu-cleoside 61a on KB cells in culture confirmed the high cytotoxic potency of this compound. Moreover, it appeared that, at low doses, where no cytotoxic effect occurs, the ketonucleoside impaired DNA, RNA, and protein synthesis, and strongly inhibited cell multiplication. 

K. Bock and C. and H, Pedersen extend the article in Vol. 41 by the first two authors, on the 13C-n.m.r. spectroscopy of monosaccharides, to a compilation of such data for oligosaccharides that should prove of great value as a source of reference. K. Antonakis (Villejuif, France) presents a discussion of ketonucleosides, compounds of interest in synthesis and in biological roles they have not hitherto been comprehensively examined in this Series. 

Three additional approaches to the synthesis of CNT are shown in Fig. 9. The first [77, 78] involves transformation of 3 -ketonucleoside 44 into cyanohydrin 45, followed by deoxygenation at 3 and then at 2 to afford 47, which is easily epimerized to 31 by treatment with base (pH = 9). Treatment of 2 -0-acyl derivatives of 46 with bases produced elimination to give the 2, 3 -unsaturated nucleoside 48. An important factor in the chemistry of these cyanonucleosides is the acidity of the H-3 hydrogen atom in a-position to the nitrile group. This acidity is responsible for the facile epimerization 47 31 and for the elimination... 

---