Preparation of 4-Pentenoic Acid Ester of Neu5Ac and 4-Pentenyl Glycoside of Neu5Ac and Their Application to Glycosylation

Abstract

N-Acetylneuraminic acids (Neu5Ac), sialic acids are most frequently found as a-glycosidically linked terminal residues of glycoproteins and glycolipids. There are a wide range of biological properties endowed by sialic acids on natural glycoconjugate structure and function, often involved in important cell surface communications and infection processes. 1-3)The development of the efficient method of O-sialylation has been a challenging task in the field of sialic acid chemistry. 4,5) Fraser-Reid and his co-workers introduced a 4-pentenyl group as a new and effective leaving group at the anomeric center of the glycosyl donor.6) The attractiveness of 4-pentenyl glycosides is enhanced by the fact that they can be applied to the armed/disarmed methodology of oligosaccharide synthesis.7) 4-Pentenyl glycosides are of interest for studying various biological and physiological phenomena of carbohydrates.8) To the best of our knowledge, there has been no report on the synthesis of 4-pentenoic acid ester of Neu5Ac (1a). A few reports 9,10) on the synthesis of 4-pentenyl glycoside of Neu5Ac (1b) have been reported, however application of 1b to O-sialylation has not been studied. As a part of our program aimed at the development of new O-sialylation, 11,12) we are interested in finding out whether 1a, b would be suitable for stereoselective O-sialylation. This paper describes the synthesis of 1a, b and their application to O-sialylation. Results and DiscussionWe first focused on an efficient synthesis of 1a having 4-pentenoyloxy group at the 2-position of Neu5Ac as a leaving group. Treatment of per-O-acetylated Neu5Ac 2 with hydrogen chloride in AcCl-AcOH (1 : 1) gave 2-chloro derivative 3 in a quantitative yield. Compound 3 was treated with silver carbonate in acetone-H 2 O (9 : 1) to afford 2-hydroxy derivative 4 13) in 88% yield. Acylation of 4 was achieved by 4-pentenoic anhydride and pyridine and N,N-dimethylaminopyridine (DMAP) in CH 2 Cl 2 to give 1a in a quantitative yield as an anomeric mixture with b-anomer as the major product (Chart 1). Next, we focused on a search for an efficient method of synthesizing 1b. When silver salicylate was used as a promoter in the presence of 4-penten-1-ol in CH 2 Cl 2 , 1b was obtained in 80% yield.9) The best result was obtained when the reaction was performed by Koenigs-Knorr condi- * To whom correspondence should be addressed. e-mail: ikeda@u-shizuoka-ken.ac. Novel sialosyl donors, 4-pentenoic acid ester of N-acetylneuraminic acids (Neu5Ac) (1a) and 4-pentenyl glycoside of Neu5Ac (1b) were successfully prepared from the corresponding per-O-acetylated 2-hydroxy and 2-chloro derivatives of Neu5Ac, respectively and applied to the synthesis of O-sialosides.

A Highly Reactive and Stereoselective β‐Mannopyranosylation System: Mannosyl 4‐Pentenoate/PhSeOTf

“…Glycosyl pentenoates are not really new but have been reported as glycosyl donors with iodonium dicollidine perchlorate (IDCP) and N ‐iodosuccinimide/trifluoromethanesulfonic acid (NIS–TfOH) promoters by the research groups led by Kunz8 and Fraser‐Reid9 independently. However, no detailed studies on the stereoselectivity and no application to oligosaccharide synthesis have been reported,10 except that sialyl 4‐pentenoate is reported to be inferior to 4‐pentenyl sialoside as a glycosyl donor 11. Herein we describe the use of 1 as the glycosyl donor and PhSeOTf as the promoter for the synthesis of β‐mannopyranosides and the efficient construction of an oligosaccharide.…”