Synthesis and Glycosidation of Anomeric Halides: Evolution from Early Studies to Modern Methods of the 21st Century

Abstract

Advances in synthetic carbohydrate chemistry have dramatically improved access to common glycans. However, many novel methods still fail to adequately address challenges associated with chemical glycosylation and glycan synthesis. Since a challenge of glycosylation has remained, scientists have been frequently returning to the traditional glycosyl donors. This review is dedicated to glycosyl halides that have played crucial roles in shaping the field of glycosciences and continue to pave the way toward our understanding of chemical glycosylation.

Figure 1.

Mechanistic interpretation of action of hydroxyl carboxylate and dicarboxylate silver salts.

Figure 2.

Contradicting reactivity trends in the cooperatively catalyzed Koenigs–Knorr glycosylations.

Figure 3.

Linear oligosaccharides syntheses using Koenigs–Knorr (A) and halide-catalyzed (B) approaches

Scheme 1.

Outline of General Glycosylation Mechanisms

Scheme 2.

First Glycosylation Reactions Reported by Michael (A), Koenigs and Knorr (B), and Fischer (C)

Scheme 3.

First Attempts to Enhance Utility of the Koenigs–Knorr Reaction

Scheme 4.

Glycosidation of 1,2-cis and 1,2-trans Glycosyl Halides and the Formation of 1,2-Orthoesters

Scheme 5.

Synthesis of Glycosyl Bromides from Unprotected Sugars and Glycosyl Esters

Scheme 6.

Synthesis of Glycosyl Bromides from Thioglycosides (A), Hemiacetals (B), and O-Glycosides (C)

Scheme 7.

Silver Silicate-Promoted Glycosidation of 2-Deoxy- and 2,6-Dideoxyglycosyl Bromides

Scheme 8.

Borinic Acid-Catalyzed Glycosidation of Glycosyl Bromide

Scheme 9.

Regenerative Glycosylation

Scheme 10.

TMSOTf-Catalyzed Koenigs–Knorr Glycosylation

Scheme 11.

Cooperatively Catalyzed Koenigs–Knorr Glycosylation in Polar and Nonpolar Solvents

Scheme 12.

Acyl Group-Directed α-Stereoselective Galactosylation in Cooperatively Catalyzed Glycosylations

Scheme 13.

Visible Light-Mediated Cu(I)-Catalyzed 1,2-cis α-Selective Glycosylation

Scheme 14.

Visible Light-Mediated Intermolecular Addition of Glycosyl Bromide to Methyl Acrylate

Scheme 15.

Mercury Salt-Promoted Glycosidations of Glycosyl Bromides

Scheme 16.

Glycosylation and Anomerization in Zinc Salt-Promoted Glycosylations

Scheme 17.

Cadmium Salt-Promoted Glycosylation

Scheme 18.

Indium Salt-Promoted Glycosidations of Glycosyl Bromides

Scheme 19.

Tin Salt-Mediated Glycosidation of Glycosyl Bromides

Scheme 20.

Bismuth(III) Salt-Promoted Activation of Glycosyl Halides

Scheme 21.

Reaction of Glycosyl Bromide 4 in the Presence of Pyridine

Scheme 22.

Synthesis of α-Glycoside via Positively Charged Glycosyl Donors

Scheme 23.

1,2-cis Glycosylation via β-Phenanthrolium Intermediates

Scheme 24.

Formation of 1,2-cis Glycosides via In Situ Anomerization

Scheme 25.

Iodine or Iodine Monobromide/Chloride-Promoted Glycosylations

Scheme 26.

Bromine-Promoted α-Selective Glycosylations

Scheme 27.

NIS-TfOH-Promoted Glycosidation of Glycosyl Bromides

Scheme 28.

Examples of Alcoholysis Reactions

Scheme 29.

Convergent Synthesis of Heptasaccharide 117

Scheme 30.

Phenanthroline-Catalyzed Synthesis of 1,2-cis Glycans

Scheme 31.

Selective Activation Utilizing Three Leaving Groups

Scheme 32.

In Situ Activation of Thioglycosides via Bromides

Scheme 33.

Oligosaccharide Synthesis via Regenerative Glycosylation

Scheme 34.

Synthesis of Glycosyl Chlorides from Ethers or Hemiacetals

Scheme 35.

New Methods for the Synthesis of Glycosyl Chlorides

Scheme 36.

Direct Synthesis of Glycosyl Chlorides from Thioglycosides

Scheme 37.

Cadmium or Tin Salt-Promoted Glycosidations of Glycosyl Chlorides

Scheme 38.

Silver Triflate-Promoted Activation of Sialic Acid Chlorides

Scheme 39.

Organoboron-Catalyzed Glycosidation of 2-Deoxy and 2,6-Dideoxy Glycosyl Chlorides

Scheme 40.

Glycosyl Chloride Activation Using Ag₂O and TfOH Promoter System

Scheme 41.

Glycosyl Chloride Activation Using Thioureas

Scheme 42.

Halogen Bond-Mediated Activation of Glycosyl Chloride

Scheme 43.

Glycosyl Chloride Activation Using Catalytic FeCl₃

Scheme 44.

Bismuth(III)- and Palladium(II)-Catalyzed Activations of Glycosyl Chlorides

Scheme 45.

Selective Activation of Sialyl Chloride 142 over Sialyl Fluoride 167

Scheme 46.

Anomerization of Glycosyl Iodides

Scheme 47.

Synthesis of C-Glycosides Using Glycosyl Iodides

Scheme 48.

Synthesis of O-Glycosides Using Glycosyl Iodides

Scheme 49.

Glycosidation of Iodides of Different Series

Scheme 50.

Dehydrative Glycosidation of Hemiacetals

Scheme 51.

Iterative Synthesis of Trisaccharide 196 Using Glycosyl Iodides

Scheme 52.

Synthesis of Glycosyl Fluorides from Acetates

Scheme 53.

Synthesis of Glycosyl Fluorides from Other Halides

Scheme 54.

Synthesis of Glycosyl Fluorides from Hemiacetals

Scheme 55.

Synthesis of Glycosyl Fluorides from Chalcone Glycosides

Scheme 56.

Synthesis of Glycosyl Fluorides from Other Starting Materials

Scheme 57.

Glycosidation of Glycosyl Fluoride in the Presence of Tin(II)-Based Reagents

Scheme 58.

Glycosidation of Glycosyl Fluoride in the Presence of Other Tin-Based Reagents

Scheme 59.

Glycosidation of Glycosyl Fluoride in the Presence of Silicon-Based Reagents

Scheme 60.

Glycosidation of Glycosyl Fluoride in the Presence of Boron-Based Reagents

Scheme 61.

Glycosyl Fluoride Activation with Main Group Metal Salts

Scheme 62.

Glycosyl Fluoride Activation with Transition Metals Salts

Scheme 63.

Glycosyl Fluoride Activation with Lanthanide Metals Salts

Scheme 64.

Other Methods for the Activation of Glycosyl Fluorides

Scheme 65.

Convergent Assembly of High Mannose Type N-Glycan

Scheme 66.

Borane-Catalyzed Convergent Oligosaccharides Synthesis

Scheme 67.

Two-Step Activation with Fluorides and Thioglycosides

Scheme 68.

Orthogonal Activation Was Discovered with Fluorides and Thioglycosides

Scheme 69.

Orthogonal Synthesis on Solid Phase

Scheme 70.

Ionic Liquid-Tagged Synthesis of Mannans

Scheme 71.

Synthesis of Xylans 320 Using an Engineered Xylanase