Synthese und Umwandlungen von Isoxazolidin‐Nucleosiden

Abstract

Synthesis and Transformations of Isoxazolidine‐Nucleosides Reaction of the oxime 12 with formaldehyde, acetaldehyde or acetone in the presence of methacrylic acid methylester leads in a highly stereoselective 1,3 dipolar cycloaddition of the corresponding nitrones to the protected isoxazolidine ribosides 13, 14, 20, 21 and 26 ( Scheme 1 and 2 ). Using a new, mild procedure to effect detriylation, the cycloaddition products were transformed into the alcohols 16–19 , 22–25 and 27 . Cleavage of a mixture of the glycosides 16 and 17 yielded the N ‐unsubstituted isoxazolidine 29 in 65% optical purity while the cleavage of 27 gave optically pure 28 . Alternatively, the isoxazolidine ribosides 13, 14, 16–18 and 26 were transformed via reductive cleavage of the isoxazolidine N‐O bond and subsequent lactamization into the corresponding pyrrolidinone‐ribosides 30, 33, 35, 42, 49 and 50 , the ribitolyl pyrrolidinones 31, 34, 36–39 and 43–46 (see Scheme 4 ) and the ribitolyl isoxazolidine 47 .