Solid-phase synthesis complex carbohydrates

The first by Manzi and Keifer discussed the acquisition of NMR data of microgram quantities of complex carbohydrates using Nano-probe technology.196 Later in 1997, Keifer197 reviewed the utilization of Nano-probe technology in solid-phase synthesis and combinatorial chemistry. 

A complex synthesis of the precursors and the sophisticated coupling-deprotection steps restricted the common use of the proposed solid phase synthesis approach, while the liquid phase synthesis is still a reasonable alternative for most carbohydrate chemists. Nevertheless, the perspectives of solid phase synthesis are not questioned with increased commercial... 

Automated solid phase synthesis, which has enabled synthesis libraries of peptides (15) and nucleic acids (16) and their use in drug discovery, is emerging as a useful tool for carbohydrate production (17). This technology has been difficult to develop largely due to the aforementioned inherent complexity of carbohydrates (18). Both nucleic acids and proteins can be assembled only in head-to-tail chains, whereas a chain of carbohydrates has the potential to elongate at any one of five different points on the sugar and these linkages can... 

There have been several recent solid-phase and solution-phase libraries reported that contain the spiroketal moiety (Figure 7.5). These libraries introduce additional structural complexity and new interaction modes of carbohydrate-like molecules with biological targets. Ley and cowoikers reported the solid-supported synthesis of spiroketals. Using stereoselective aldol reactions of boron enolates, the Waldmann and Paterson groups reported the solid-phase synthesis of 6,6-spiioketals. The 1,7-dioxaspiro [5.5]undecane spiroketal served as the core template for Porco s three-point diversity library to explore protein-protein interactions. ... 

Automated carbohydrate synthesis allows for the production of complex carbohydrates orders of magnitude faster than other approaches. This advance has the potential to parallel the breakthroughs achieved by researchers in the peptide and DNA fields that opened up the pro-teomic and genomic eras in biotechnology. By increasing the scope of the carbohydrate building block library and streamlining the reaction conditions further we anticipate that automated solid-phase carbohydrate synthesis will become the method of choice for carbohydrate production. 

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