Halo sugars

Verheyden, J.P.H. and Moffatt, J.G., Halo sugar nucleosides. I. Iodination of the primary hydroxyl groups of nucleosides with methyltriphenoxyphospho-nium iodide, /. Org. Chem., 35, 2319, 1970. 

J. P. Verheyden and J. G. Moffatt, Halo sugar nucleosides. III. Reactions for the chlorination and bromination of nucleoside hydroxy groups, J. Org. Chem. 37 2289 (1972). 

The radical is generated on the sugar template using mostly the tin hydride method and halo derivatives [72,87,89], thionocarbonate [90-91], or selenium derivatives [91,94, 95]. Again, in these reactions, the kinetically controlled 5-exo cyclization is always... 

A. Carbocycles from unsaturated halo sugars by hex-5-enyl... 

A. Carbocycles from Unsaturated Halo Sugars by Hex-5-enyl Radical Cyclizatlon [8]... 

C. S. Wilcox and L. M. Thomasco, New syntheses of carbocycles from carbohydrates. Cycliza-tion of radicals derived from unsaturated halo sugars, J. Org. Chem. 50 546 (1985) see also S. Hanessian, D. S. Dhanoa, and P, L. Beaulieu, Synthesis of tt-substituted a,P-unsaturated esters via radical-induced cyclizations, Can. J. Chem. 65 1859 (1987). 

The reaction has found little application so far however, one of the first examples of an asymmetric synthesis using peroxidases was the highly regio- and diastereo-selective halohydration of glycals to 2-deoxy-2-halo sugars in the presence of CPO [263]. Some examples of selective halogenation reactions of aromatic compounds using CPO optimized by directed evolution approaches are also known [264]. 

After it was demonstrated that silylated sugars easily form diglycosides225 when they are applied to 1-halo-sugars, further studies followed. It became apparent that these silylated heterocycles are convenient intermediates, especially for the synthesis of nucleosides when acylated 1-halo-sugar are employed224,22S. ... 

Epoxy sugars are frequently used as starting compounds in the synthesis of sugar derivatives (compare Section IV) such as halo, amino, azido, thio, deoxy, and branched-chain derivatives. The oxirane ring is in general more reactive than the oxetane or oxolane ring. It is opened with nucleophiles under base or acid catalysis. On the other hand, the oxirane ring remains unattacked under the conditions of catalytic debenzylation on palladium,... 

Oxidation of aldoses by hypoiodite can also be used for preparative purposes.7 Other types of halogen oxidants, especially A-halo compounds, are useful. For example, A -bromocarbamide was recommended by Kiss8 as a selective and convenient reagent for oxidizing benzylated sugars to their corresponding aldonolactones in yields exceeding 90%. Another example is the use of A-iodosuccinimide and tetrabutylammonium iodide.9... 

Similarly, heptamethyltrisilane (K), heptamethyltrisilanethiol (L), 5,10-dihydro-disilanthracene (M) also reduce organic halides and xanthates, though the reactivities are decreased and they cannot be used for C-C bond formation [18, 19]. Reagent (N) is water-soluble monosilane and it can reduce sugar halides and halo-nucleosides in water [20]. However, the reactivity is low and it can only be used for the reduction of organic... 

A number of cyclic and sugar-derived halo acetals 273 were subjected to radical 5-exo cyclizations catalyzed by a cobalt salen catalyst 274 with NaB H4 as the stoichiometric reductant but in the presence of air (entry 11) [321, 322]. Under these conditions, bicyclic oxygenated tetrahydrofurans 275a were obtained in 50-84% yield. Diastereomeric isomers 275b were isolated as the minor components. The yields were similar to those obtained with tributyltin hydride. The oxygen concentration proved to be important, since air gave better yields... 

In 1970, 1 was prepared by direct glycosylation of the silylated 5-azacytosine with acylated 1-halo sugars, but the yields were very low.20 In this procedure, 1,3,5-tri-O-acetyl-2-deoxy-D-ribofuranose (9) was converted into 3,5-di-0-acetyl-2-deoxy-D-ribofuranosyl chloride (10).21 The trimethylsilyl derivative of 5-azacytosine (11),22 prepared from 4-amino-6-pyrimidine by treatment with hexamethyldisilazane, was then allowed to react with intermediate 10 in acetonitrile over 7 days to give a mixture of anomers of l-(3,5-di-(9-acetyl-2-deoxy-D-ribofuranosyl)-5-azacytosine (12) in 10% overall yield. The anomeric mixture was treated with ethanolic ammonia to remove the acetyl groups. The resulting a and p anomers were separated by a combination of fractional crystallization and preparative layer chromatography on silica gel to give pure decitabine (1) and its a-anomer 13 in 7% and 52% yield, respectively. 

The interest in the sugar derivatives of some of these systems as isosteres of purine nucleosides has led to considerable research into their direct electrophilic coupling reactions with halo-sugars or other activated sugars. Generally however, electrophilic attack occurs at several positions as is evident with 7-amino-1,2,3-triazolo[4,5-t/]pyrimidine (54a), the so-called 8-azaadenine , giving rise... 

Halo-sugars are very useful building blocks for designing further reactions by substitution of halogen atoms. From these compounds, we have developed a che-moenzymatic strategy giving 5-thio-D-xylose in four steps (the key step being catalyzed by FruA). 

Heterocondensed uracils are easily accessible from acyllactones, -lactams, -thiollactones (72S151), and heterocyclic /3-enamino esters, especially (85AHC299). The latter gives a broad range of novel types of condensed systems. With the aid of the hexamethyldisilazane trimethyl-chlorosilane (HMDS/TMSC1) technique or the use of NaH and halo-sugars, respectively, simple approaches have been developed to obtain unusual nucleosides [92JPR(ip)] (Scheme 15). 

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