Jiří Kroutil

Aziridine Ring Cleavage by Nucleophiles in Epimino Derivatives of 1,6-Anhydro-β-D-hexopyranoses

The regioselectivity of aziridine ring cleavage by nucleophiles (Cl−, Br−, I−, N3−, HBr) in a series of N-tosyl- and N-benzylepimino derivatives of 1,6-anhydro-β-D-hexopyranoses of D-allo, D-manno and D-galacto configurations has been studied. On treatment with halide anions, the tosylepimines 1, 3, 5 and 7 were opened trans-diaxially according to the Furst−Plattner rule. The courses of the reactions of benzylepimines 2, 4, 6 and 8 depended strongly on the configuration of the epimine and partially on the type of nucleophile used. On treatment with bromide and iodide, N-benzylepimines of D-allo (compounds 2, 4) and D-galacto (compound 6) configuration gave products of trans-diequatorial cleavage, while the manno-epimine 8 was opened trans-diaxially. In comparison, the reactions of all benzylepimines with azide and hydrobromic acid were independent of the configuration and proceeded trans-diaxially. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of All Configurational Isomers of 1,6-Anhydro-2,3,4-trideoxy-2,3-epimino-4-fluoro-β-d-hexopyranoses

We have prepared a full series of 1,6-anhydro-2,3,4-trideoxy-4-fluoro-2,3-epimino-beta-d-hexopyranoses. The key step was the reaction of azido sulfonates possessing a free C-4 hydroxyl with DAST and subsequent LiAlH(4) reduction. Nucleophilic displacement of the hydroxyl activated by DAST proceeded without rearrangement and with moderate to good yields. A convenient synthesis of d-mannoepimine from a readily available 3-benzylamino derivative was also developed.

Chemistry of Carbohydrate Aziridines

Publisher Summary This chapter discusses the chemistry of carbohydrate aziridines, with emphasis being placed on surveying preparative methods and ring-opening reactions. Carbohydrate aziridines or epimines are derivatives in which an aziridine ring is fused to a pyranose or furanose ring or to an exocyclic part of a carbohydrate molecule. From the mechanistic point of view, the reported syntheses of carbohydrate aziridines are based almost exclusively on S N 2 intramolecular nucleophilic substitution. The nucleophile is a nitrogen-containing group, often free or an N -substituted amino group, which can be generated in situ by the reduction of an azido or cyano group, or by the Michael addition of amines to a double bond with appropriate substitution. The neighboring leaving group is typically an alkyl (aryl)sulfonyloxy group, or is generated in situ , which is the case with the Mitsunobu reaction. The aziridine-ring closure invariably proceeds with the inversion of configuration at the atom bearing the leaving group. The stereochemistry of S N 2 nucleophilic substitution strongly favors the antiperiplanar disposition of the participating groups in the transition state. This chapter describes the methods for the synthesis of carbohydrate aziridines. It also explains the general properties of carbohydrate aziridines and elaborates the reactions of carbohydrate aziridines.

Synthesis of S-linked glucosaminyl-4-thiohex-2-enopyranosides via allylic SN2′ substitution of a tosylhexenose

Treatment of 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-beta-D-glucopyranose with 1,6-anhydro-3,4-dideoxy-2-O-p-toluenesulfonyl-beta-D-erythro-hex-3-enopyranose gave 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-glucopyranosyl-(1-->4)-1,6-anhydro-2,3-dideoxy-4-thio-beta-D-erythro-hex-2-enopyranose in 86% yield. Its 1,6-anhydride bond was cleaved with methanol to give a mixture of methyl glycosides (alpha/beta approximately 5:1), from which the alpha anomer was separated by crystallization and converted into its 6-acetate, 6-methanesulfonate, or deacetylated to obtain the corresponding free methyl thiodisaccharide. The structure of the new compounds was confirmed by 1H and 13C NMR spectra.