Random glycosylation

Dzumela and McGarvey have recently described plans for the preparation of an oligosaccharide library using what they describe as the sulfoxide random glycosylation method.40 They have synthesized 128 and 129 as a prelude to this exercise (Fig. 3.5). 

Figure 12.8 Protein binding to two random glycosylation libraries.

On the basis of the early results described above, random glycosylation as an approach to oligosaccharide library preparation has been further pursued. The product distributions in these early reactions were difficult to determine, and in subsequent work, the aglycon of the acceptor was changed to the p-methoxyphenoxy octyl... 

To facilitate the analysis of random glycosylation reactions, all six possible products (13-18) were synthesized as reference standards to simplify the determination of product distributions.11 These standards could be separated on a PAC column permitting direct analysis of mixtures by HPLC. A typical chromatogram of a separation of a random glycosylation is shown in Figure 12.9. 

Early on, random glycosylation of unprotected disaccharides, involving the nonselec-tive coupling of a fucosyl donor, was used to produce three sub-libraries of a-fucosylated disaccharides in one step (136). Nearly statistical mixtures of all possible trisaccharides were obtained after chromatography. Linear and branched trisaccharide libraries were prepared by the latent-active glycosylation (137, 138). This concept made use of the convenient access to both glycosyl donors and acceptors from common allyl glycoside precursors. 

Combinatorial methods for the identification of biologically active carbohydrates are evolving. Generation of random glycosylation-based libraries as heterogeneous mixtures have given way to focused libraries that employ discrete saccharide cores. 

Scheme 16.12. Oligosaccharide synthesis by a random glycosylation strategy.

With the advent of combinatorial chemistry new problems are raised for writers of review material which refers to specific compounds. Thus, the random glycosylation of an W-acetyllactosaminide with an L-fucosylating agent affords a... 

Figure 3. The solution phase random glycosylation of the unprotected disaccharide A with the trichloroacetimidate donor B trisaccharides in nearly equal amounts.

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