The field of carbohydrate chemistry has occupied the minds and hearts of many scientists for over a hundred years and, as we enter the twenty-first century, it continues to be both vigorous and challenging. Among the most exciting aspects of organic chemistry in the last few decades has been the interplay between the specialized subdisciplines of carbohydrate chemistry and total synthesis, each enabling and advancing the other in new directions and towards greater heights. In this review article we highlight our own adventures at the interface of these disciplines, which were driven for the most part by objectives in chemical synthesis and chemical biology. Specifically, we describe our interests and efforts to utilize carbohydrates as starting materials for total synthesis, to invent and develop new synthetic technologies for carbohydrate synthesis, to construct complex oligosaccharides in solution or on solid support, and to utilize carbohydrate templates as scaffolds for peptide mimetics and for molecular diversity construction. Finally, applications of the developed synthetic strategies and enabling technologies towards the solution of biologically significant problems are discussed.

Adventures in Carbohydrate Chemistry: New Synthetic Technologies, Chemical Synthesis, Molecular Design, and Chemical Biology

Strategies in Oligosaccharide Synthesis

Repeating glycosidic linkages of oligosaccharides can be synthesized by solid-phase methods. Glycals were attached to a polystyrene copolymer with a silyl ether bond and were activated to function as glycosyl donors with 3,3-dimethyldioxirane. Glycosidation was performed by reactions with a solution-based acceptor (itself a glycal). Excess acceptor and promoter were removed by rinsing after each coupling, and the desired oligosaccharides were then easily obtained from the polymer by the addition of tetra-n-butylammonium fluoride. By this method, glycosidations are stereospecific and interior deletions are avoided.

https://science.sciencemag.org/content/sci/260/5112/1307.full.pdf

A strategy for the solid-phase synthesis of oligosaccharides

Umpolung-based strategies play a significant role in organic synthesis. Particularly important are 1,3-dithiane linchpins, which serve as convenient acyl anion equivalents. The general synthetic accessibility and impressive reactivity of 1,3-dithianes have thus led to widespread application. Since the late 1970s, dithianes have featured prominently in our program directed toward the synthesis of complex natural and unnatural products, both for effective union of advanced fragments and for multicomponent linchpin couplings. In this Account, we present the evolution of dithiane chemistry in our laboratory.

Evolution of Dithiane-Based Strategies for the Construction of Architecturally Complex Natural Products

Advances in carbohydrate chemistry have certainly made common oligosaccharides much more accessible. However, many current methods still rely heavily upon specialized knowledge of carbohydrate chemistry. The application of automated technologies to chemical and life science applications such as genomics and proteomics represents a vibrant field. These automated technologies also present opportunities for their application to organic synthesis, including that of the synthesis of oligosaccharides. However, application of automated methods to the synthesis of carbohydrates is an underdeveloped area as compared to other classes of biomolecules. The overarching goal of this review article is to present the advances that have been made at the interface of carbohydrate chemistry and automated technology.

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Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges.

Synthese d'oligosaccharides a partir de tri-O-benzyl-3,4,6 glucal, de di-O-benzoyl-3,4 glucal et d'hexofuranoses ou d'hexopyranoses proteges

On the controlled oxidative coupling of glycals: a new strategy for the rapid assembly of oligosaccharides

Application of substituent-controlled oxidative coupling of glycals in a synthesis and structural corroboration of ciclamycin 0: new possibilities for the construction of hybrid anthracyclines

On the use of the haloetherification method to synthesize fully functionalized disaccharides

Application of Substituent-Controlled Oxidative Coupling of Glycals in a Synthesis and Structural Corroboration of Ciclamycin 0: New Possibilities for the Construction of Hybrid Anthracyclines.

Synthetic routes to the fully functionalized α-linked disaccharides 19 21 and 25 are described starting from a common intermediate the iodo acetate 15. This substance was in turn prepared via a haloetherification reaction between the allal derivative 13 the galactose alcohol 14 and an “iodonium” equivalent.

Richard W. Friesen

Papers

On the controlled oxidative coupling of glycals: a new strategy for the rapid assembly of oligosaccharides

Application of substituent-controlled oxidative coupling of glycals in a synthesis and structural corroboration of ciclamycin 0: new possibilities for the construction of hybrid anthracyclines

On the use of the haloetherification method to synthesize fully functionalized disaccharides

Application of Substituent-Controlled Oxidative Coupling of Glycals in a Synthesis and Structural Corroboration of Ciclamycin 0: New Possibilities for the Construction of Hybrid Anthracyclines.

On the Use of the Haloetherification Method to Synthesize Fully Functionalized Disaccharides.