A combinatorial approach to recognition of chirality:: Preparation of highly enantioselective aryl-dihydropyrimidine selectors for chiral HPLC
A combinatorial approach to recognition of chirality:: Preparation of highly enantioselective aryl-dihydropyrimidine selectors for chiral HPLC
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DOI：
10.1021/cc980014p
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发表时间：
1999-01-01
影响因子：
--
通讯作者：
Fréchet, JMJ
中科院分区：
文献类型：
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作者：
Lewandowski, K;Murer, P;Fréchet, JMJ
使用单步 Biginelli 多组分缩合合成了 108 种 4-芳基-1,4-二氢嘧啶 (DHPM) 对映体的平行文库，这些对映体是手性 HPLC 分离的潜在选择器。通过观察“刷型”L-(3,5-二硝基苯甲酰基)亮氨酸手性固定相上拆分的对映选择性来筛选各个化合物，分离因子 α 高达 12。文库中的最佳候选物在嘧啶环的 C4 碳原子处含有邻位取代的芳香基团，在 N1 氮原子处含有烷基取代基。使用半制备手性 HPLC 拆分先导化合物 4-(9-菲基)-DHPM 8 的对映体，然后连接到单分散大孔氨基甲基丙烯酸酯珠上，提供了基于新型聚合物的手性固定相，在拆分几种吡酸芳基二氢嘧啶时具有良好的对映选择性，并且 衍生化的洛芬。此外，α-氨基酸的3,5-二硝基苯甲酰氨基衍生物可以在正相HPLC条件下分离，分离因子高达8。
A parallel Library of 108 4-aryl-1,4-dihydropyrimidine (DHPM) enantiomers, which are potential selectors for chiral HPLC separations, was synthesized using the single-step Biginelli multicomponent condensation. The individual compounds were screened by observing the enantioselectivity for resolution on a "brush-type" L-(3,5-dinitrobenzoyl)leucine-based chiral stationary phase, and separation factors alpha up to 12 were achieved. The best candidates from the library contained an ortho-substituted aromatic group at C4 carbon atom of the pyrimidine ring and an alkyl substituent at N1 nitrogen atom. Resolution of the enantiomers of the lead compound, 4-(9-phenanthryl)-DHPM 8, using semipreparative chiral HPLC followed by attachment to monodisperse macroporous aminomethacrylate beads, provided the novel polymer based chiral stationary phase with good enantioselectivities in the resolution of several pi-acidic aryl-dihydropyrimidines and derivatized profens. In addition, 3,5-dinitrobenzamido derivatives of alpha-amino acids could be resolved under normal phase HPLC conditions with separation factors up to 8.