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New method for organic synthesis based on affinity separation

基于亲和分离的有机合成新方法

基本信息

批准号：
12640571
负责人：
FUKASE Koichi
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12640571/
关键词：
affinity separation oligosaccharide peptide molecular recognition high through put synthesis glycoconjugate lipid A library ピリドA タグ固相合成

项目摘要

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.

本文提出了一种新的高通量合成方法--亲和分离合成法（SAS）。该反应在溶液中进行并且所需产物可以通过固体载体和具有主体和客体结构的所需产物之间的主体-客体相互作用而快速分离，冠醚（32-冠-10）和铵离子之间的相互作用先前被发现可用于此目的。合成开始于用冠醚标记的起始材料。在每个反应循环后，将反应混合物施加到氨甲基化聚苯乙烯柱（三氟乙酸形式）上。具有冠醚的化合物被选择性地吸附在柱上，而没有冠醚的其他杂质如过量的试剂和副产物被洗掉。用CH_2CL_2-MeOH（1：1）洗脱，得到目标化合物，产率高。然后我们发现Triton X-100（聚乙二醇基洗涤剂）可以代替32-冠-10作为标记物。巴比妥酸衍生物与它的人工受体[=双（2，6-二氨基吡啶）氨基丙酸]之间的相互作用也被发现是有效的。这两种方法都适用于合成肽，杂环，和寡糖。利用后一种方法，实现了一种新的高效合成脂质A的方法。脂质A是一种具有免疫刺激作用的细菌糖缀合物。利用该方法构建了脂质A小文库。这些新的策略预计将是有用的，特别是，多个平行合成和组合库的制备。