Carbohydrate Chemistry

Proven Synthetic Methods, Volume 5

Paul Kosma, Tanja M. Wrodnigg, Arnold Stütz

• Publisher: CRC Press
• Year: 2021
• ISBN:
  9781351256063
• Edition: 1
• Topic: Medicine
• Subtopic: Biochemistry in Medicine

Volumes in the Proven Synthetic Methods Series address the concerns many chemists have regarding irreproducibility of synthetic protocols, lack of identification and characterization data for new compounds, and inflated yields reported in chemical communications—trends that have recently become a serious problem.

Exploring carbohydrate chemistry from both the academic and industrial points of view, this unique resource brings together useful information into one convenient reference. The series is unique among other synthetic literature in the carbohydrate field in that, to ensure reproducibility, an independent checker has verified the experimental parts involved by repeating the protocols or using the methods.

Featuring contributions from world-renowned experts and overseen by a highly respected series editor, this latest volume compiles reliable protocols for the preparation of intermediates for carbohydrate synthesis or other uses in the glycosciences.

Key Features:

• Explains reliable and tested protocols for the preparation of intermediates for carbohydrate synthesis
• Offers a unique resource in glycosciences, compiling useful information in one reference
• Presents protocols that are of wide use to a broad range of readers in the carbohydrate field and the life sciences, including undergraduates taking carbohydrate workshops
• Explores synthetic carbohydrate chemistry from both the academic and industrial points of view
• Guarantees the reader a good, clean, reproducible experiment

Part I

Synthetic Methods

1

Synthesis of Glycosyl Thiols via 1,4-Dithiothreitol-Mediated Selective Anomeric S-Deacetylation

Lei Cai, Yan Liu, Xiong Xiao, Jing Zeng, Qian Wan^*

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Huazhong University of Science and Technology,

Wuhan, P. R. China

Han Ding^a

Key Laboratory of Marine Medicine, Chinese Ministry of Education, School of Medicine and Pharmacy, Oceans University of China,

Qingdao, P. R. China

CONTENTS

• Experimental
  • General Methods
  • General Procedure for Anomeric S-Deacetylation
  • 2,3,4-Tri-O-Acetyl-6-Deoxy-1-Thio-β-D-Galactopyranose (2A )
  • 2,3,4-Tri-O-Acetyl-6-Deoxy-1-Thio-β-D-Glucopyranose (2B )
• Acknowledgments
• References

We describe a practical method for the synthesis of glycosyl thiols (1-thiosugars) by 1,4-dithiothreitol (DTT)-mediated selective S-deacetylation. Glycosyl thiols are common building blocks for construction of S-linked glycosides, such as S-linked oligosaccharides, glycopeptides, and glycolipids.¹ The stability of S-glycosidic bond in these compounds allows for their wide application in the investigation of biological processes and the development of new therapeutics.² A convenient and practical synthesis of glycosyl thiols is based on selective S-deacylation of peracylated thioglycosides.³ However, most of the reported methods involve the use of a strong base, such as NaOH or NaOMe, and require careful control of the reaction conditions.⁴ Weaker bases, for example, Et₃N or NaSMe, have also been applied to the selective anomeric S-deacylation, but only moderate yields were reported.⁵ Recently, Zhu et al. reported an improved method applying aqueous NaSMe as base.⁶ Inspired by native chemical ligation, we have developed a cysteine mediated S-deacetylation reaction.³ This method has been further expanded to a DTT-mediated selective S-deacetylation reaction under weakly basic conditions through transthioesterification. The advantages of this method lie in mild reaction conditions, high efficiency on large scale, simple purification without column chromatography, and the ease of recovery of DTT. Herein, we present the detailed procedures of this DTT-mediated selective anomeric S-deacetylation as applied to 6-deoxy-D-pyranoses.

^aChecker: under supervision of Prof. Ming Li: [email protected]

^*Corresponding author: [email protected]

Fully acylated thiosugars (1a, 1b) reacted with DTT smoothly to produce glycosyl thiols 2a and 2b in good yields in the presence of 0.1 equiv of NaHCO₃ at room temperature (25°C) (Figure 1.1). Notably, the reaction must be quenched immediately once the starting material is completely consumed (TLC), as extended reaction times lead to formation of side products. In addition, the absence of moisture is essential, as its presence causes O-deacetylation. Furthermore, the use of DMA (N,N-dimethylacetamide) as reaction solvent is important: It allows for the isolation of the glycosyl thiols from the water-diluted reaction mixture by extraction with toluene. Normally, the products obtained by these processes are sufficiently pure for further transformations. The aqueous phase containing excess of DTT and acetylated DTT is saturated with NaCl followed by extraction with ethyl acetate. Further evaporation of ethyl acetate and treatment of the mixture of DTT and acetylated DTT with K₂CO₃ in MeOH regenerates a considerable amount of DTT. The regenerated DTT could be used in the next selective anomeric S-deacetylation without affecting the reaction efficiency.³

FIGURE 1.1 Selective anomeric S-deacetylation and the recovery and regeneration of DTT. ^aThe yields of recovered DTT in parentheses.

EXPERIMENTAL

GENERAL METHODS

All reactions were monitored by thin-layer chromatography on silica gel-coated TLC plates (HSGF 254, Yantai Chemical Industry Research Institute). The spots were visualized by charring wit...

Table of contents

• Cover
• Half Title
• Carbohydrate Chemistry: Proven Synthetic Methods
• Title Page
• Copyright Page
• Dedication
• Contents
• Foreword
• Introduction
• About the Series Editor
• About the Editors
• Contributors
• PART I SYNTHETIC METHODS
• PART II SYNTHETIC INTERMEDIATES