Protecting Groups: Strategies and Applications in Carbohydrate Chemistry

Sebastien Vidal

• Publisher: Wiley-VCH
• Year: 2018
• ISBN:
  9783527697021
• Edition: 1
• Topic: Sciences physiques
• Subtopic: Chimie physique et théorique

A unique overview of the most important protecting group strategies in carbohydrate chemistry Protecting Groups: Strategies and Applications in Carbohydrate Chemistry provides a detailed account of key strategies and methodologies for the protection of carbohydrates. Divided into two parts, the first focuses on groups that are used best to protect a specific position on a carbohydrate. In the second part, specific carbohydrate residues or compounds are discussed in the context of a specific protecting group strategy used to reach the desired regioisomer. This important book: -Features chapters on protecting groups at the primary and secondary positions of carbohydrates
-Describes protecting group strategies towards sialic acid derivatives, glycofuranoses, sulfated glycosaminoglycans, and cyclodextrins
-Provides information on automated glycan assembly
-Includes a chapter on the industrial scale synthesis of heparin analogs Written by a team of leaders in the field, Protecting Groups: Strategies and Applications in Carbohydrate Chemistry is an indispensable guide for academics and industrial researchers interested in carbohydrate and natural product synthesis, pharmaceutical chemistry, and biochemistry.

1
Protecting Group Strategies in Carbohydrate Chemistry

Anne G. Volbeda Gijs A. van der Marel and Jeroen D. C. Codée

Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands

Carbohydrates are the most densely functionalized class of biopolymers in nature. Every monosaccharide features multiple contiguous stereocenters and bears multiple hydroxyl functionalities. These can, in turn, be decorated with sulfate groups, acyl esters, lactic acid esters and ethers, or phosphate moieties. Amine and carboxylate functions can also be present. Most often, the amine groups are acetylated, but different amide functions are also found, as well as N‐sulfates and alkylated amines. The discrimination of the functional groups on a carbohydrate ring has been and continues to be one of the great challenges in synthetic carbohydrate chemistry [1–3].

This chapter describes the differences in the reactivity of the various functional groups on a carbohydrate ring and how to exploit these in the design of effective protecting group strategies. The protecting groups on a carbohydrate dictate the reactivity of the (mono)saccharide, and this chapter will describe how protecting group effects can be used to control stereoselective transformations (most importantly, glycosylation reactions) and reactivity‐controlled one‐pot synthesis strategies. Applications and strategies in automated synthesis are also highlighted.

1.1 Discriminating Different Functionalities on a Carbohydrate Ring

The main challenge in the functionalization of a carbohydrate (mono)saccharide is the discrimination of the different hydroxyl functionalities. The – often subtle – differences in reactivity can be capitalized upon to formulate effective protecting group strategies (see Scheme 1.1A). The primary alcohol functionality is generally the most reactive of the hydroxyl groups because of steric reasons (see Chapter 2). It can be site selectively addressed using bulky protecting groups such as silyl or trityl ethers. The anomeric hydroxyl group discerns itself from the other secondary hydroxyl groups in that it is part of a hemiacetal functionality (see Chapter 5). It can, therefore, be selectively modified using acetal chemistry, and acid‐catalyzed acetal and mixed thioacetal formations are among the most used methods to start a protecting group manipulation sequence. Because it is part of a hemiacetal functionality, the anomeric hydroxyl group is also the most acidic alcohol on a carbohydrate ring, and it can be chemoselectively modified under basic conditions. Conversely, it is less reactive than the other secondary alcohol groups under acidic conditions. Axial secondary alcohols are generally slightly less reactive than the equatorial ones on a carbohydrate ring, and these reactivity differences can often be exploited in designing an efficient protecting group scheme (see Chapters 3 and 4). Finally, the position of a hydroxyl group on the carbohydrate ring and the nature of its neighboring substituents affect its reactivity. In this regard, the use of cyclic protecting groups that engage two hydroxyl groups in a cyclic context (see Chapter 11) has proven to be a very powerful tool [4]. Benzylidene acetals and silylidene ketals can be used to mask C‐4 C‐6 diols, where isopropylidene groups and orthoesters are commonly employed to protect cis‐hydroxyl groups in a five‐membered ring constellation. Butane 2,3‐bisacetals and the recently introduced o‐xylylene groups can be used to protect vicinal diequatorial diols [5]. To illustrate how the reactivity of various alcohol groups can be exploited, two examples are given in Scheme 1.1B,C. The first example shows a four‐step reaction sequence that has been used to site selectively mask all groups of a glucosamine synthon 1. Thus, the nitrogen functionality in D‐glucosamine can be chemoselectively protected with a trichloroacetyl group, by virtue of its higher nucleophilicity with respect to the alcohols present. Next, the primary alcohol at C‐6 and the hydroxyl group at C‐4 can be masked with a di‐tert‐butyl silylidene ketal. The selectivity of this transformation originates from the bulky nature of the protecting group and the fact that a stable trans‐decalin system can be formed. Next, the anomeric hydroxyl group can be selectively addressed using basic conditions to install an imidate group. Finally, the remaining alcohol can be masked with a levulinoyl ester [6]. In the second example, ...

Table of contents

• Cover
• Table of Contents
• Foreword
• Preface
• 1 Protecting Group Strategies in Carbohydrate Chemistry
• 2 Protecting Groups at the Primary Position of Carbohydrates
• 3 Protecting Groups at the Secondary Positions of Carbohydrates
• 4 Regioselective Protection at the Secondary Positions of Carbohydrates with Acyclic Protecting Groups
• 5 Protecting Groups at the Anomeric Position of Carbohydrates
• 6 N‐protecting Groups for 2‐Amino‐2‐deoxy‐glycosides
• 7 One‐pot Multistep Regioselective Protection of Carbohydrates Catalyzed by Acids
• 8 Acyl Migrations in Carbohydrate Chemistry
• 9 De Novo Asymmetric Synthesis of Oligosaccharides Using Atom‐less Protecting Groups
• 10 Protecting Group Strategies for Sialic Acid Derivatives
• 11 Strategies Toward Protection of 1,2‐ and 1,3‐Diols in Carbohydrate Chemistry
• 12 Protecting Group Strategies Toward Glycofuranoses
• 13 Cyclodextrin Chemistry via Selective Protecting Group Manipulations
• 14 Protecting Group Strategies Toward Sulfated Glycosaminoglycans
• 15 Applications of Fluorous and Ionic Liquid Tags in Oligosaccharide Synthesis
• 16 Orthogonally Protected Building Blocks for Automated Glycan Assembly
• 17 Kilogram‐scale Production of Synthetic Heparin Analogs: Some Chemical Considerations
• Index
• End User License Agreement