Nitrones nucleosides

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

Isoxazole (as well as isoxazoline, and isoxazolidine) analogues of C-nucleosides related to pseudouridines 25 and 27 have been regioselectively synthesized by 1,3-dipolar cycloaddition (1,3-DC) of nitrile oxides (and nitrones) derived from uracyl-5-carbaldehyde 24 and 2,4-dimethoxypyrimidine-5-carbaldehyde 26 respectively <06T1494>. 

The reaction of silyl ketene acetal addition to nitrones has been used for the synthesis of optically active (2S,3S)-benzoyl- and /V- oc-phenyl isoserine (636a) of isoxazolidine nucleoside-analog of thymine polyoxine C(636b) and of... 

The reaction of O-methyl-O-tert-butyldimethylsilyl ketene acetal with N-benzyl- and A-methyl-2,3-O-Mopropylidene D-glyceraldehyde nitrones (292), in the presence of boron trifluoride etherate, affords the corresponding isoxazolidine-5-ones in high yields. These compounds were successfully applied as key intermediates in the synthesis of isoxazolidinyl nucleosides of the L-series (Scheme 2.177) (638). 

The reaction of 1,3-dipolar cycloaddition of enantiopure cyclic nitrones to protected allyl alcohol, is the basis of stereoselective syntheses of bicyclic N, O-iso-homonucleoside analogs (747), of isoxazolidine, to analogs of C-nucleosides related to pseudouridine (748) and to homocarbocyclic-2 -oxo-3 -azanucleosides (749) (Fig. 2.36). 

Dipolar cycloadditions of nitrones with vinyl acetate leads to 5-acetoxy-isoxazolidines, which can be easily transformed to isoxazolidinyl nucleosides by the Vorbriieggen methodology (803). 

Nitro compounds, synthesis of, 12, 3 Nitrone-olefin cycloadditions, 36, 1 Nitrosation, 2, 6 7, 6 Nucleosides, synthesis of, 55, 1... 

S. Sahabuddin, A. Roy, M. G. B. Drew, B. G. Roy, B. Achari, and S. B. Mandal, Sequential ringclosing metathesis and nitrone cycloaddition on glucose-derived substrates A divergent approach to analogues of spiroannulated carbanucleosides and conformationally locked nucleosides, J. Org. Chem., 71 (2006) 5980-5992. 

Among a number of other homochiral furanosyl- and isoxazolidinylthymine targets, these workers also applied an achiral cycloaddition approach with vinyl acetate to successfully prepare the antiviral agent d4T (11) and its 2-methyl analogue (Fig. 1.1) (45). In more recent work, similar nitrones [9, R = Me or benzyl (Bn)] were used to prepare hydroxymethyl substituted isoxazolidines [3-(46) and 3,5-substituted (47)] for the preparation of further nucleoside analogues. 

A number of workers have described the synthesis and cycloaddition reactions of oxazoline nitrone dipoles, (e.g., 361 and 362, Scheme 1.80) (413 17). A homochiral oxazoline nitrone derived from camphor has been used to great effect by Langlois and co-workers (418,419), from which they have prepared a number of natural targets through enantioselective cycloaddition reactions, including the antiviral carbocyclic nucleoside analogue (+)-carbovir (48) (Fig. 1.1, Section 1.3). 

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