Nucleosides 6-halogeno

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. 

M. Ikebara and H. Miki, Studies of nucleosides and nucleotides. LXXXH Cyclonucleosides. (39). Synthesis and Properties of 2 -halogeno-2 -deoxyadenosines, Chem. Pharm Butt. 26 2449 (1978). 

Ikehara, M. and Imura, J. (1981) Studies on nucleosides and nucleotides. LXXXIX. Purine cyclonucleosides. (43). Synthesis and properties of 2 -halogeno-2 -deoxyguanosines. Chem. Pharm. Bull., 29, 3281-3285. 

Cushley, R. J., Codington, J. F. and Fox, J. J. (1968) Nucleosides. XLIX. Nuclear magnetic resonance studies of 2 -and 3 -halogeno nucleosides. The conformations of 2 -deoxy-2 -fluorouridine and 3 -dcoxy-3 -(l Lioro-jl-D-arabi noliiranosyl uraci I. Can. J. Client., 46, 1131-1140. 

Synthesis.—By Cycloaddition. The Noyori cycloaddition of halogeno-ketones to furans is now sufficiently well established to provide a firm base for the successful synthesis of C-nucleosides. For example, the ketone (109) has been prepared ... 

Dideoxynucleosides can also be prepared by hydrogenolysis of 2, 3 -dideoxy-2 -thio [158], 2, 3 -dideoxy-3 -thio [159, 160], 8,3 -S-anhydronucleo-sides of purine [161] and 2, 3 -dideoxy-3 -halogenoderivatives of nucleosides [52,162,163]. The intermediate dideoxy-3 -thio and 3 -halogeno derivatives can be easily prepared by nucleophilic displacement of the sulfonyloxy group of 2 -deoxy-3 -0-mesyl or tosyl nucleosides with mercaptide anion or with halide ion, respectively. The procedure has been successfully used for the synthesis of 3 -deoxythymidine 109h, 2, 3 -dideoxyuridine 109i and 2, 3 -dideoxy-5-... 

Treatment of 5-deoxy-5-halogeno nucleosides of adenine and uracil with trimethylamine yielded the corresponding 5-deoxy-5-trimethylammonium salts, whose interaction with anionic polynucleotides was then examined. Various A -alkyl, A -cycloalkyl, and iV-alkaryl derivatives of 3-amino-3-deoxy-and 3, 5 -diamino-3, 5 -dideoxy-adenosine have been prepared from the amino-sugar nucleosides the 3 -benzylamino derivative gave the unusual oxazolidine derivative (52). ° ... 

Reference to nucleosides containing halogeno-sugars is made in... 

Halogeno-sugar and Amino-sugar Nucleosides Thionucleosides... 

The synthesis of radiolabelled halogeno-nucleosides is included in Chapter 20, while the use of halogeno-sugars in synthesis is referred to in Chapters 12 and 13. 

Figure 13.4. Structures of AZT and 3 -azido-2, 3, 4 -trideoxy-5-halogeno-4 -thio-fi-D-uridine nucleosides.

Deoxy-2-halogeno-arabinosyl bromides have been used to prepare halo-nucleosides from 5-substituted-uracil or -cytosine bases leading to 2 -bromo, 2 -chloro, and 2 -fluoro-arabino-nucleoside analogues the 2 -fluoro analogues were most effective as anti-viral 48... 

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