Anomeric radicals nucleosides

A. Kittaka, T. Asakura, T. Kuze, H. Tanaka, N. Yamada, K. T. Nakamura, and T. Miyasaka, Cyclization reactions of nucleoside anomeric radical with olefin tethered on base Factors that induce anomeric stereochemistry,/. Org. Chem., 64 (1999) 7081-7093. 

While numerous applications of anomeric radicals exist, three examples serve to illustrate possible future applications and directions for this chemistry. Barton has developed a short and convergent synthesis of the C-nucleoside showdomycin 292 (Scheme 80) [127]. Kessler has prepared an interesting C-linked glycopeptide unit 294 via radical addition to a dehydroaminoacid acceptor 293 (Scheme 81) [137]. In the latter example, good anomeric stereo-... 

There has been a further report on the formation of C-nucleosides by reaction of anomeric radicals (formed by decarboxylation) with heterocycles (see Vol. 25, p.260). ... 

Synthesis of spiro sugars and C-nucleosides using anomeric free radicals 98SL700. 

Saccharidic Difluorophosphonates Difluoromethylene phospho-nates have been the focus of numerous works. Indeed, these compounds are able to mimic the phosphate bond in the synthesis of enzyme inhibitors. This interest is obvious for the furanose series in this case, they are non scissible analogues of 5-phosphate nucleosides (cf. Chapter 7). Difluoromethylene phosphonates can be prepared via a radical path starting from compounds that have the difluoromethylene moiety in the pseudo-anomeric position. Nevertheless, methods based on metal derivatives of difluorophosphonates are generally easier and broadly applicable. 

The use of the hypervalent iodine reagent [bis(trifluoroacetoxy)iodo]benzene has been reported to be effective in the synthesis of C-nucleoside-like compounds. Radical decarboxylation of a suitably protected uronic acid, initiated photochem-ically, followed by addition of a heterocyclic base provided the C-nucleoside in high yield.154 The mode of action involves initial radical formation of 122 (Scheme 33), followed by introduction of the base and radical coupling.155 The anomeric selectivity was high in some examples, and low in others—lepidine gave the highest proportion of the ( anomer. Isolated yields were poor to moderate. 

The marked stereoselectivity of these radical reactions must be ascribed to the effect of the bulk of the protecting groups. However, the radicals that were manipulated may have also shown an anomeric effect due to the vicinal oxygen. In a furanose sugar it is not easy to evaluate the anomeric effect without ESR, and also, the molecules concerned have two fused five-membered rings. This fixes the conformation into a V-shape. Such molecules are well known to have exo-reactivity and the formation of endo-bonds is difficult. All these effects may be acting together to make this nucleoside chemistry especially stereospecific. 

Tetrahydrofurans are known to be less conformationally rigid than their 6-membered ring counterparts, and hence anomeric effects in these systems also tend to be less pronounced. In the reactions of 2-tetrahydrofuranyl radicals, stereoselectivities tend to be dictated by steric rather than electronic effects [13]. With respect to C-1 nucleoside radicals, both Tanaka and Chatgilialoglu have independently reported methods for forming these species via 1,2-acyloxy migration and... 

There have been further reports on pyridine C-nucleosides. 4-Carbam-oyl-2-p-D-ribofuranosylpyridine 54 and 3-carbamoyl-5-P-D-xylofuranosyl-pyridinel55 have been prepared by Alderweireldt s approach (see Vol. 21, p. 211), and some 2 -deoxy-r,2 -didehydro-pyridine C-nucleosides have been prepared by base-catalyzed elimination. Addition of lithiopyridines to 2,3-C-isopropylidene-5-C-TBDMS-D-ribonolactone gives adducts such as (133), which can be reduced to p-pyridyl C-nucleosides with EtaSiH.l T Coupling of the anomeric free radical, produced by photolysis of an iV-acyl-thiohydroxamate, with pyridinium and quinolinium salts gave 2-pyridyl C-nucleosides and 2-quinolinyl systems such as (135), where P-selectivity was... 

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