SummaryThe separate, radical denitration with Bu3SnH of the pyranose derivatives 3, 4, 9, and 10 gave in good yields exclusively the 'C-glycosides' 5 and 11, respectively (Scheme 1). Similar reduction of the cyclohexyl derivatives 15, 16, 19 and 20 gave 4:l mixtures of 17, 18, 21 and 22, respectively, always with predominant formation of an axial C,H-bond. In the furanose series a divergent behaviour was observed for the D-mannose-derived nitro ethers 25 and 27 and the D-ribose-derived nitro ethers 30 and 31, respectively, in that the former two gave isomerically homogeneous reduction products (26 and 28, respectively; Scheme 3) and the latter a 1 : 1 mixture of the diastereoisomers 32 and 33 (Scheme 4). The stereochemical results were explained on the basis of the stereoelectronic effect of the ring O-atom, the preferred conformation of the intermediate, pyramidal alkoxyalkyl radicals and steric effects in the trioxabicyclo [3.3.0]octane ring system. As far as it is known, these reactions follow a radical-chain mechanism and proceed via planar radical intermediates. As expected, the few stereochemically relevant reductions so far studied occur without stereospecificity [2] and with a variable diastereoselectivity [7] which is difficult to predict2).In the case of conformationally biased n-nitro ethers, however, the analogous reductive denitrations are expected to occur with a high degree of diastereoselectivi ty .

A synthesis of N‐acetylneuraminic acid (1) and of N‐acetyl‐4‐epineuraminic acid (2, R = H) from 2‐acetamido‐4,6‐O‐benzylidene‐1,2‐dideoxy‐1‐nitro‐D‐mannopyranose (3) and 2‐acetamido‐1,2‐dideoxy‐4,6‐O‐isopropylidene‐1‐nitro‐D‐mannopyranose (4), respectively, is described. Michael addition of 3 and 4 to tert‐butyl 2‐(bromomethyl)prop‐2‐enoate (5) and subsequent hydrolytic removal of the NO2 group gave the 4‐nonulosonate tautomers 6/7 and 8/9, respectively (Scheme). Stereoselective reduction of 6/7 and 8/9 with NaBH4/AcOH in dioxane/H2O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6/7 and 8/9 in the absence of AcOH or in EtOH gave 12/13 (15:85) and 14/15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert‐butyl neuraminate 22 and tert‐butyl 4‐epineuraminate 24, respectively. Ozonolysis of 14/15, separation of the products 20 and 21, and hydrolytic removal of the isopropylidene groups gave 22 and 24, respectively. The tert‐butyl ester 22 was saponified to give 1, which was further characterized as the methyl ester 23. Saponification of 24 gave the crude 4‐epimer of 1, which was converted into the stable Na salt 2 and also into the methyl ester 25.

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1-C-Nitroglycals. Preparation and Reaction with Some Nitrogen NucleophilesAcetylation of the I-deoxy-1-nitromannopyranoses 2 and 6 was accompagnied by spontanous 8-elimination to give the 1-C-nitroglucals 3 and 7, respectively, while acetylation of the gluco-and galucto-contigurated I-deoxy-1-nitropyranoses 8 and 14 gave the acetates 9 and 15, respectively (Scheme I). The acetylation of the riboand urahino-contigurated I-deoxy-I-nitrofuranoses 19 and 21 also occurred without 8-elimination to give the acetates 20 and 22, respectively (Scheme 2). Mild base treatment of the previously described U-acetylnitro-B-oglucose 4, the 0-acetylnitro-/I-D-pyranoses 9 and 15, and the 0-acetylnitro-8-D-furanoses 17, 20, and 22 gave the I-C-nitroglycals 3,10,16,18 and 23, respectively (Scheme I and 2). The previously obtained I-C-nitroglucal3 was deacetylated by treatment with MeOH in the presence of KCN or sodium m-nitrophenolate to give the free nitroglucal 5. Deacetylation of the benzylidene protected I-C-nitroglucal 10 (MeOH, NaOMe) gave the 4,643-benzylidene-I-C-nitroglucal 11 and traces of the 2-0-methyl-1-C-nitromannoses 12 and 13. The UV, IR, 'H-NMR and I3C-NMR spectra of the I-C-nitroglycals are discussed. In solution, the I-C-nitroglycals 1, 5,7,10,11, and 16 adopt approximately a 4H5-and 3 a flattened 4H5 conformation. The structure of 5 was established by X-ray analysis. In the solid state, 5 adopts a sofa conformation, which is stabilized by an intramolecular H-bond. The 8-addition of NH, to the 1-C-nitroglucals 7 and 10 was followed by an O+N acetyl migration to give exclusively anomeric pairs of the N-acetyl-1-nitromannosamine derivatives 24/25 and 26/27, respectively (Scheme 3). The /I-addition of methylamine, octadecylamine, and tryptamine to the 1-C-nitroglucal 11 also stereoelectronically controlled and gave the crystalline N-alkyl-1-nitromannosamines 28,29, and 30, respectively. The stereoelectronically controlled /I-addition of NH, to the 1-C-nitrogalactal 16, followed by acetylation, yielded exclusively the talosamine derivative 31, while the reversible 8-addition of azide ions to 16 gave the anomeric 2-azido-I-nitrogalactoses 32 and 33. The @-addition of azide ions to the I-C-nitroglucal 1 led to the 2-azido-I-nitromannose 34. In the presence of excess formaldehyde, this addition was followed by a Henry reaction. Chromatography of the crude product was accompagnied by solvolytic removal of the NOz group to give the 3-azidomannoheptulose 35 in high yields (Scheme 4 ) .

The synthesis of the 6-amino-6-deoxysialic-acid analogues 4,5, and 6 is described. Mitsunobu reaction of the 1-C-nitroglycal8 (PPh,, HCOOH, DEAD) gave the formiate 10 with inversion of configuration at C(3) (Scheme 2). Treatment of 10 with aq. NH, and subsequent protection of the amino function gave the imines 14 and 15 (Scheme 3 ) , which were transformed into the triflates 17. Substitution by azide, deprotection, and N-acetylation gave the anomeric 2-acetamido-3-azido-I-deoxy-1-nitro-D-mannoses 16 and the enol ether 18. Chain elongation of the nitro azides 16 followed by hydrolysis gave the nonulosonates 20/22, which upon reduction yielded the diols 23 and 24, respectively (Scheme 4 ) . The diol 23 was transformed into the sialic-acid analogues 5, 6, and 32 by ozonolysis, transfer hydrogenation, hydrogenolysis, and deprotection (Scheme 5 ) . and the diol 24 into 4 by a similar reaction sequence. The sialic-acid analogues 4 and 6 inhibit bacterial and viral sialidases competitively. The inhibitor constants for this enzyme from Vibrio cholerae are 0.12 mM for 4 and 0.19 mM for 6, respectively. The activity of fowl plague virus sialidase was reduced by 17% and 36% under the influence of 4 and 6, respectively, at a concentration of 0.1 mM. Compound 5 was inactive. Several sialidase inhibitors are known [16][17][18][19][20], e.g. N-acetyl-2-deoxyneur-2-enaminic acid ('2,3-dehydro-N-acetylneuraminic acid'; Neu2enSAc) [2 11 [22], N-acetyl-2-deoxy-4-epineur-Zenaminic acid (4epiNeu2enSAc) [22] [23], and N-acetyl-2-deoxy-4-oxoneur-2-