Anomeric Samarium(III) Intermediates of N-Acetylneuraminic Acid from Anomeric 2-Pyridylsulfides

Abstract

Treatment of the anomeric 2-thiopyridyl derivative of N-acetylneuraminic acid (sialic acid or Neu5Ac) with samarium diiodide in the presence of aldehydes or ketones provides the corresponding C-sialylated derivatives in excellent yields.The efficiency of the reductive samariation of the anomeric 2-pyridylsulfide moiety in the Neu5Ac series does not require any cosolvent or additive.This samarium Reformatsky-like reaction from anomeric 2-pyridylsulfide derivatives of Neu5Ac provides an efficient and highly stereoselective access to α-2,6-C-disaccharides.N-Acetylneuraminic acid (Neu5Ac) is the more common nine-carbon member of the ulosonic acids family, that are important constituents of numerous oligosaccharides and glycoconjugates. 1 The terminal position of the Neu5Ac residues in these conjugates confer a major role to these structures in many biological processes. 2,3The α-glycosidic linkage of this important structural unit exhibits however poor chemical and enzymatic hydrolytic stability thus providing unstable tools for biological research.The replacement of the interglycosidic oxygen by a carbon atom provides carbon-linked analogues (C-glycosides) that are stable to hydrolysis. 4 Based on our previous work on neutral aldoses 5 and 2-acetamido-2-deoxy-sugars, 6 Linhardt and coworkers 7 have reported, over the past years, efficient and stereoselective access to C-glycosides of Neu5Ac based on the reductive metallation of anomeric aryl sulfones and chloride.In an effort to further simplify the preparation of the anomeric organometallic precursor, our laboratory previously reported procedures that rely on the reductive samariation of standard peracetylated intermediates 8 and subsequent coupling with carbonyl electrophiles.Along these