Saccharide synthesis

Oligo- and Poly-saccharide Synthesis with Sucrose Analogues... 

C. J. Hamilton, Enzymes in preparative mono- and oligo-saccharide synthesis, Nat. Prod. Rep., 21 (2004) 365-385. 

From a historic perspective glycosyl chlorides and bromides introduced, respectively, by Michael [2] and Koenigs and Knorr [3] were the most widely used donors in the saccharide synthesis for a very long time. The introduction of 1,2-orthoesters in 1964 [4] was the first important attempt to find an alternative to the Koenigs-Knorr method. However, Paulsen in his 1990 review of reliable donors for glycosyl... 

Scheme 5.18 Kong and coworkers one-pot method for saccharide synthesis. Reaction conditions (i) 2,4-lutidine, AgOTf, molecular sieves (ii)TMSOTf, 0°C.

There are several other indirect and special methods that have not found any broader application for glycoside and saccharide synthesis yet but that might be useful for certain cases or might develop into more common procedures in the future. Such other indirect and special methods are discussed in this chapter. 

The protection of amino groups of amino sugars benefits particularly from the use of new blocking groups introduced for peptide synthesis. In this context, light-sensitive urethans and amides that can be utilized for the protection of amino groups in amino sugars are of particular interest in saccharide synthesis and modification. 

Table II (104) shows the results of an experiment to learn the proportion of a-D-glucosyl fluoride that is hydrolyzed vs. that used for saccharide synthesis by the different crystalline a-amylases and by diluted saliva. The substrate was again 0.2 M and the enzymes at one-tenth to one-one hundredth the concentrations of the preceding experiment. These digests were analyzed directly for amounts of fluoride (104, 107) and D-glucose (glucose oxidase method) liberated during 2 hours at 30°C.

Table II. Saccharide Synthesis vs. a-D-Glucosyl Fluoride Hydrolysis by Different a-Amylases °...

K. B. Sharpless Application of asymmetric epoxidation in saccharide synthesis... 

Methylenation of 58 with an excess of the Takai reagent and subsequent RCM with the second generation Grubbs catalyst 7 (35 mol%) gave an intermediate (bis)-C-glycal which was directly subjected to hydroboration by BH3 THF and subsequent oxidative work-up to afford the C-trisaccharide 60 in 49% yield over three steps (26). Although double RCM reactions are known (27), this was the first time it has been used in the context of C-saccharide synthesis. 

The Trichloroacetimidate Method Application to Glycoside and Saccharide Synthesis... 

Due to the drawbacks of the Fischer-Helferich method it was early recognized that other approaches to glycoside and saccharide synthesis had to be introduced. 

A versatile and generally applicable method for a didstereocontrolled glycoside and saccharide synthesis seems to necessitate a two-step procedure with the following requirements. ... 

N-glycoside synthesis. The simplicity of the procedure offers valuable additions to glycoside and saccharide synthesis. 

T. Ziegler, E. Eckhardt, and V. Birault, Synthetic studies toward pyruvate acetal containing saccharides. Synthesis of the carbohydrate part of the Mycobacterium smegmatis pentasaccharide glycolipid and fragments thereof for the preparation of neoantigens,./. Org. Chem., 58 (1993) 1090-1099. 

Saccharide synthesis in vivo is a very complex process that is not regulated by universally conserved codes, and has not been automated in vitro yet. Ultimately, in order to provide useful quantities of materials a combination of chemical and enzymatic techniques is necessary. 

Biocatalytic synthetic pathways are very attractive as they have many advantages such as mild reaction conditions, high enantio-, regio-, chemoselectivity and are nontoxic natural catalysts. In enzymatic methods for glycoside and saccharide synthesis no selective protection/deprotection steps are necessary and control of configuration at newly formed anomeric centers is absolute. 

Two approaches have dominated enzyme-catalyzed saccharide synthesis glyco-syl transferase and glycosidase-catalyzed glycosidic bond formation. The first uses the normal biosynthetic machinery of living organisms. In the second, enzymes that normally catalyze transfer of an enzyme-bound glycosyl residue to water are induced to transfer it instead to a different acceptor. 

A rule of thumb in classical complex saccharide synthesis is that the addition of each monosaccharide unit requires on an average seven steps. Although there have been striking improvements in synthetic methods in recent years, the synthesis of a trisaccharide, for example, can still take 10 or more steps. The application of glycosidases to the synthesis of complex hetero-oligosaccharides represents a considerable saving in time and materials, and hence in overall cost. 

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