New method for organic synthesis based on affinity separation

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A new method named synthesis based on affinity separation (SAS) was developed for high throughput synthesis : the reaction is carried out in solution and the desired products can be isolated rapidly by the host-guest interaction between the solid-support and the desired products which possess the host and guest structures, respectively.The interaction between crown ether (32-crown-10) and ammonium ion was previously found to be useful for this purpose. The synthesis started with a starting material tagged with the crown ether. After each reaction cycle, the reaction mixture was applied to the aminomethylated polystyrene column (trifluoroacetic acid form). The compound possessing the crown ether was selectively adsorbed on the column, whereas other impurities without the crown ether such as excess reagents and byproducts were washed off. Subsequent desorption with CH_2CL_2-MeOH (1 : 1) afforded the desired compound in high yield. We then found Triton X-100 (polyethylene glycol based detergent) can be used as a tag in place of 32-crown-10.The interaction between a barbituric acid derivative and its artificial receptor [= bis(2,6-diaminopyridine)amide of isophthalic acid] was also found to be effective. Both methods were applied to the synthesis of peptides, heterocycles, and oligosaccharides. New efficient synthesis of lipid A, an immunostimulating glycoconjugate of bacteria, was achieved by using the latter method. The small lipid A library was also constructed by the method. These new strategies are expected to be useful for, particularly, multiple parallel synthesis and combinatorial library preparation.