Diastereoselective Synthesis of d-erythro- and d-threo-Isoxazolidinyl ­Nucleosides

Eva Hýrošová; Lubor Fišera; Jozef Kožíšek; Marek Fronc

doi:10.1055/s-2008-1042942

PAPER

Diastereoselective Synthesis of d-erythro- and d-threo-Isoxazolidinyl Nucleosides

Eva Hýrošová^a, Lubor Fišera*^a, Jozef Kožíšek^b, Marek Fronc^b
^a Institute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinskeho 9, 81237 Bratislava, Slovak Republic
Fax: +421(2)52968560; e-Mail: lubor.fisera@stuba.sk;
^b Institute of Physical Chemistry and Chemical Physics, Slovak University of Technology, Radlinskeho 9, 81237 Bratislava, Slovak Republic

Abstract

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Abstract

The synthesis of isoxazolidinyl nucleosides based on the Vorbrüggen nucleosidation of 5-acetoxyisoxazolidines 5 and 9 is reported. The 1,3-dipolar cycloaddition of d-erythro-nitrone 4 with vinyl acetate proceeded with respectable anti-facial (84:16) and endo-facial (72:28) diastereoselectivity to give the diastereomeric isoxazolidines 5-7. The reaction of d-threo-nitrone 8 with vinyl acetate is more selective and proceeds with excellent anti-facial preference producing only two diastereomers 9 and 10, although four diastereomers are possible. The condensation of the acetoxyisoxazolidines 5 and 9 with silylated uracil, thymine, N-acetylcytosine, N ²-acetylguanine, and purines proceeded with moderate to excellent stereoselectivity with formation of the expected isoxazolidinyl β- and α-nucleosides. The stereoselectivity of the addition of silylated nucleobase is depended on the structure of the substituent at C3 originating from the starting chiral nitrone and on the attacking nucleobase.

Key words

nucleosides - isoxazolidines - cycloadditions - C-glycosyl nitrones - stereoselective synthesis

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References

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Diastereoselective Synthesis of d-erythro- and d-threo-Isoxazolidinyl ­Nucleosides

Diastereoselective Synthesis of d-erythro- and d-threo-Isoxazolidinyl Nucleosides