Library oligosaccharides

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). 

Applications Using these protocols, an oligosaccharide library was prepared (Table 11.2). The synthesis of a tetrasaccharide in general, takes 3-15 min, and with the aid of the computer program, a library of individual oligosaccharides can be assembled rapidly. 

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... 

Figure 12.10 Creating random oligosaccharide libraries using the p-methoxyphenoxy octyl group as the aglycon.

A similar approach to create an oligosaccharide library was reported using a glycal and diols as the donor and acceptor to produce stereospecific regiorandom mixture of glycosides (Fig. 12.12).15 a-Specific glycosylations were achieved via addition of... 

Figure 12.12 Formation of an oligosaccharide library using glycal and diols as donor and acceptor, respectively, to produce a stereospecific regiorandom glycoside mixture.

Takahashi et al.45 used a 4-hydroxybenzenesulfonate linker on Syn-Phase polystyrene Crowns to prepare glucose derivatives and macrocycles (Scheme 20). Displacement of the monosaccharide-supported Crowns 70 with nucleophiles such as azide, iodide, and acetate gave the respective 6-substituted glucose derivatives 71, 72, and 73 in excellent purities and yields. The authors suggest that this methodology could be utilized for the preparation of oligosaccharide libraries. 

In the synthesis of diverse oligosaccharide libraries, a conventional SPOS methodology would involve laborious solution-phase preparation of many building blocks and that number would increase if increased diversity of the library is to be obtained. To develop a versatile and practical approach, it is necessary to reduce the number of building blocks ideally... 

Fig. 11. Combinatorial oligosaccharide library approach in solution with an orthogonal...

The use of microfluidic systems in oligosaccharide synthesis is in its infancy and far from being automated. More extensive use and development of such systems will open up new ways to access high-throughput and combinatorial oligosaccharide libraries. 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

While these advances make the synthesis of di-and trisaccharide combinatorial libraries a relatively facile process, the synthesis of oligosaccharide libraries (such as tetrasaccharides and higher derivatives) is still quite challenging. This is largely due to the fact that the present glycosylation methods are not quantitative. 

Ito Y, Hikino M, Yajima Y, Mikami T, Sirko S, von Holst A, Faissner A, Fukui S, Sugahara K. Structural characterization of the epitopes of the monoclonal antibodies 473HD, CS-56, and MO-225 specific for chondroitin sulfate D-type using the oligosaccharide library. Glycobiology 2005 15 593-603. 

Yamago S, Yamada T, Ito H, Hara O, Mino Y, Yoshida J. Combinatorial synthesis of an oligosaccharide library by using beta-bromoglycoside-mediated iterative glycosylation of seleno-glycosides rapid expansion of molecular diversity with simple building blocks. Chem. Eur. J. 2005 11 6159-6174. 

Jemth P, Smeds E, Do AT, Habuchi H, Kimata K, Lindahl U, Kusche-Gullberg M. Oligosaccharide library-based assessment of heparan sulfate 6-O-sulfotransferase substrate specificity. J. Biol. Chem. 2003 278(27) 24371-24376. 

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