Solid-Phase Synthesis of Complex Oligosaccharides

OLIGOSACCHARIDE SYNTHESIS ON SOLID, SOLUBLE POLYMER, AND TAG SUPPORTS 

General condiUone 1/18 for automated solid-phase synthesis of 58 

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Glycosyl phosphates, building blocks in automated solid-phase synthesis of complex oligosaccharides, were prepared via a 1,2-epoxide (O Scheme 13). Oxidation of the appropriately substituted D-glucal 28 with DMDO followed by reaction with dialkyl phosphate provided the -phosphate 33, which anomerized further to the a-analog [31]. 

X. Wu and R. R. Schmidt, Solid-phase synthesis of complex oligosaccharides using a novel capping reagent,./. Org. Chem., 69 (2004) 1853—1857. 

Silyl ethers of aliphatic alcohols are inert towards strong bases, oxidants (ozone [81], Dess-Martin periodinane [605], iodonium salts [610,611], sulfur trioxide-pyridine complex [398]), and weak acids (e.g., 1 mol/L HC02H in DCM [605]), but can be selectively cleaved by treatment with HF in pyridine or with TBAF (Table 3.32). Phenols can also be linked to insoluble supports as silyl ethers, but these are less stable than alkyl silyl ethers and can even be cleaved by treatment with acyl halides under basic reaction conditions [595], Silyl ether attachment has been successfully used for the solid-phase synthesis of oligosaccharides [600,601,612,613] and peptides [614]. 

The automated solid-phase synthesis of oligosaccharides was first reported in 2001 [38], A peptide synthesizer was modified to enable solid-phase oligosaccharide synthesis. The synthesizer was equipped with a cooling system for low-temperature glycosylations. As in the case with other automated platforms, a combination of new technologies and synthetic methods were developed, and distinctive breakthroughs were achieved. Many state-of-the-art synthetic and analytical methods were adopted and adjusted over the years. The first decade of automated solid-phase oligosaccharide synthesis relied on the development of new methods to access complex structures (Fig. 7.3). 

The preceding sections discussed the strengths and weaknesses of the donor- and acceptor-bound synthetic strategies developed to date for the synthesis of complex oligosaccharides. Boons et al. recently described an approach that combines both strategies in a bidirectional solid phase oligosaccharide synthesis [67]. 

Over the past year, solid-phase synthesis approaches have been employed to tackle the preparation of a number of complex natural and synthetic targets. Fraser-Reid, Geysen et al. reported the solid-phase synthesis of oligosaccharides [100], which adds to... 

Initial attempts at solid-phase oligosaccharide synthesis (SPOS) were met with little success due to the limited range of glycosylation methods [98], It was not until much later when new methods emerged that SPOS was reexplored and has achieved remarkable success in the construction of complex oligosaccharides. 

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