Synthesis and Isolation of Diastereomeric Anomeric Sulfoxides from a d-Mannuronate Thioglycoside Building Block

Eleni Dimitriou,Gavin J Miller

doi:10.3390/m1111

Abstract

Methyl [S-phenyl 4-O-acetyl-2,3-di-O-benzyl-1-thio-α-d-mannopyranoside (R/S)S-oxide] uronate was synthesised from a thioglycoside mannosyl uronate donor in a 98% yield. By using one equivalent of meta-chloroperbenzoic acid (m-CPBA) as the sulphur oxidant, a smooth conversion to the diastereomeric sulfoxide products was achieved. The product was fully characterized by 1H, 13C and 2D NMR alongside MS analysis.

Highlights

Glycosyl sulfoxides have been successfully used as glycosyl donors within carbohydrate synthesis ever since a report by Kahne and co-workers in which they activated an anomeric sulfoxide with triflic anhydride to glycosylate a deoxycholic ester derivative [1]
Glycosyl sulfoxides are traditionally formed by the careful oxidation of a parent thioglycoside component to form an S-oxide, typically by using meta-chloroperbenzoic acid (m-CPBA) as the oxidant, other methods, including OXONE®, have recently been developed [3,4]
Whilst the oxidation generally proceeds to yield diastereomeric mixtures, stereoselective sulfoxidations have been reported for particular classes of parent thioglycosides, e.g., α-mannopyranose thioglycosides [5,6,7]

Summary

Introduction

Glycosyl sulfoxides have been successfully used as glycosyl donors within carbohydrate synthesis ever since a report by Kahne and co-workers in which they activated an anomeric sulfoxide with triflic anhydride to glycosylate a deoxycholic ester derivative [1]. Glycosyl sulfoxides are traditionally formed by the careful oxidation of a parent thioglycoside component to form an S-oxide, typically by using meta-chloroperbenzoic acid (m-CPBA) as the oxidant, other methods, including OXONE® , have recently been developed [3,4]. Whilst the oxidation generally proceeds to yield diastereomeric mixtures, stereoselective sulfoxidations have been reported for particular classes of parent thioglycosides, e.g., α-mannopyranose thioglycosides [5,6,7]. Uronic acids, where the C6 pyranosyl carbon is at the carboxylic acid oxidation level, have been prepared as glycosyl sulfoxide donors for the synthesis of oligosaccharide targets that contain d-glucuronic acid [8]. As part of a wider project concerning the chemical synthesis of alginate oligosaccharides [9], we required access to a d-mannuronic acid glycosyl sulfoxide building block (3). Provide here our record of its synthesis and full characterization from S-phenyl thioglycoside (2)

Results

General

C NMR signals were