Stereoselective Conjugate Addition of Nitrogen and Carbon Nucleophiles to Sugar-Derived Enones: Synthesis of Sialic Acid Analogues
✍ Scribed by Alessandro Dondoni; Alberto Marra; Alessia Boscarato
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 211 KB
- Volume
- 5
- Category
- Article
- ISSN
- 0947-6539
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✦ Synopsis
The conjugate addition of benzylamine to three polyalkoxy a,benones derived from d-glyceraldehyde, d-erythrose, and d-mannose, whose carbonyls were flanked by the thiazole ring, proceeded with modest to good synselectivity. The resulting polyalkoxy bamino ketones were converted by ketalization into methyl 1-(2-thiazolyl)-pyranosides that in turn were transformed into 4-amino-3,4-dideoxy-ulosonic acids by sequential cleavage of the thiazole ring into the formyl group and oxidation of the latter to carboxylate. Thus, starting from the enone derived from d-mannose, the 4-acetamido-nonulosonic acid iso-Neu4Ac, a positional isomer of sialic acid Neu5Ac, was prepared. Because of some unsatisfactory reactions, a more efficient synthesis of iso-Neu4Ac was carried out by the use of trimethylsilyl azide as a nitrogen nucleophile in the initial conjugate addition reaction. Also, in the presence of DBU the addition of nitromethane to the same enones proceeded with good syn-selectivity and chemical yield. The cyclization of the resulting ketones afforded methyl 3-nitromethyl-1-(2-thiazolyl)-pyranosides. Furthermore, the pyranoside derived from the enone incorporating the d-mannose moiety afforded after reduction of the nitro to the amino group and carboxylate generation from the thiazole ring, a 4-acetamidomethyl-3,4-dideoxy-ulosonic acid, which is a branched one-carbon higher homologue of iso-Neu4Ac.