Synthesis of chiral calixarenes and application as functional organic catalysts

通过对取代苯酚二聚体(2-(5-甲基水杨基)-4-叔丁基苯酚和(5-tert-butyl-11-methyl-17，23-diphenyl-25，26，27，28-tetrahydroxycalix醇)的裂解-缩合反应，根据K.No和同事的多步法，合成了具有三种不同上缘取代基的手性杯[4]芳烃(3-(3-hydroxymethyl-5-phenylsalicyl)-5-phenyl-2-hydroxybenzyl[4]芳烃)的外消旋混合物。另一方面，以N-(苯氧甲酰基)-D(L)-氨基酸为原料，通过羧基与对硝基苯酚和二环己基碳二亚胺的酯化反应，合成了Z-D(L)-丙氨酸-PNP，Z-D(L)-Trp-PNP氨基酸酯。杯[4]芳烃和氨基酸酯的结构经元素分析、比旋光度、红外光谱和核磁共振光谱确证。对于杯[4]芳烃催化的Z-D(L)-Trp-PNP在Z-L-Phe-OH存在下的水解，根据速率常数观察到轻微的抑制作用。尤其是D-底物的水解率略低于L底物。此外，计算机模拟(分子力学)研究表明，杯[4]芳烃将采用“锥形”构象。这些结果表明杯[4]芳烃可以与Z-D(L)-Trp-PNP形成包合物。手性杯[4]芳烃的立体化学排列可能导致了Z-D(L)-Trp-PNP的对映体选择性。

The racemic mixture of chiral calix [4]arenes (5-tert-butyl-11-methyl-17,23-diphenyl-25,26,27,28-tetrahydroxycalix [4]arene) with three different upper rim substituents was synthesized by the fragmentation-condensation of p-substituted phenol dimmers (2-(5-methylsalicyl)-4-tert-butylphenol and 3-(3-hydroxymethyl-5-phenylsalicyl)-5-phenyl-2-hydroxybenzyl alchol) according to K. No and coworkers' multi-step method. On the other hand, amino acid esters (Z-D(L)-Ala-PNP, Z-D(L)-Trp-PNP) were prepared from N-(benzyloxycarbonyl)-D(L)-amino acids by esterification of the COOH group with p-nitrophenol and dicyclohexylcarbodiimide. The calix[4]arenes and amino acid esters were confirmed by elemental analysis, specific rotation, IR and NMR spectroscopic measurements. With respect to the hydrolysis of Z-D(L)-Trp-PNP mediated by the calix[4]arenes in the presence of Z-L-Phe-OH, a little inhibition effect was observed on the basis of the rate constants. Particularly, the hydrolysis of D-substrate tended to be slightly slower than that of L-substrate. Furthermore, the computer modeling (molecular mechanics) studies indicated that the calix[4]arene would adopt a "cone" conformation. These results suggest that the calix[4]arenes could form inclusion complexes with Z-D(L)-Trp-PNP. Probably, the stereochemical arrangements of the chiral calix[4]arenes may induce the enantioselectivity for the hydrolysis of Z-D(L)-Trp-PNP.