The conjugate addition of benzylamine to three polyalkoxy α,β-enones derived from D-glyceraldehyde, D-erythrose, and D-mannose, whose carbonyls were flanked by the thiazole ring, proceeded with modest to good syn-selectivity. The resulting polyalkoxy β-amino 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.
Stereoselective conjugate addition of nitrogen and carbon nucleophiles to sugar-derived enones: Synthesis of sialic acid analogues
DONDONI, Alessandro;MARRA, Alberto;
1999
Abstract
The conjugate addition of benzylamine to three polyalkoxy α,β-enones derived from D-glyceraldehyde, D-erythrose, and D-mannose, whose carbonyls were flanked by the thiazole ring, proceeded with modest to good syn-selectivity. The resulting polyalkoxy β-amino 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
