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Hydrophobically Assisted Switching Phase Synthesis:  The Flexible Combination of Solid-Phase and Solution-Phase Reactions Employed for Oligosaccharide Preparation

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Leibniz Institute for Molecular Pharmacology (FMP), 13125 Berlin, Germany, Institute for Chemistry, Organic Chemistry, Free University of Berlin, 14195 Berlin, Germany, and Institute for Organic Chemistry, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany
Cite this: J. Am. Chem. Soc. 2005, 127, 20, 7296–7297
Publication Date (Web):April 28, 2005
Copyright © 2005 American Chemical Society

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    Hydrophobically assisted switching phase (HASP) synthesis is a concept that allows the choice between the advantages of solid-supported chemistry and those of solution-phase synthesis. Starting from the examination of adsorption and desorption properties of hydrophobic molecules to and from reversed-phase silica, we designed a dilipid as a quantitative and fully reversible HASP anchor, permitting final product release. The utility of this new tool in synthetic organic chemistry was demonstrated on oligosaccharide preparation. The synthesis of a pentarhamnoside was accomplished by repetitive glycosylation reactions. Glycosylations were conducted preferably in solution, whereas all protecting group manipulations were performed on solid support. Without the need for chromatographic purification of intermediates, the HASP system furnished the final product after 12 linear steps with average yields of 94% per step at a scale of 0.1 mmol, thus overcoming several of the limitations encountered in the solid-phase synthesis of complex carbohydrates.

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     Leibniz Institute for Molecular Pharmacology.

     University of Tübingen.


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