ИСТИНА

Optically active chiral macrocycles such as calixarenes have attracted considerable attention in recent decades in the development of enantioselective host molecules, ligands for metal catalysts, and even organocatalysts. Among them, the inherently chiral calixarenes are particularly important due to their ability to create a multifunctional asymmetric environment that can tightly ‘embrace’ chiral guest species. Nevertheless, effective synthesis approaches to ‘true’ inherently chiral calixarenes, which have an asymmetric arrangement of various functional groups in the macrocyclic core, are still very limited. Herein we report a facile and flexible approach to the synthesis of racemization-robust enantiomers of cone calix[4]arenes possessing inherent chirality due to asymmetric substitution pattern at the wide rim of the macrocycle. The introduction of two tert-butoxycarbonyl protecting groups into the proximal positions of the readily available calix[4]arene triamine was used as a key asymmetrization step. The insertion of (R)-mandelic acid residue as an auxiliary chiral unit to the remaining free amide group enabled early-step separation of stereoisomers, which allowed for further derivatization of the enantiopure calixarene cores. In this way, three pairs of optically active enantiomers of inherently chiral calix[4]arenes bearing two proximal triazole groups at the wide rims accompanied with amine, sulfonamide or urea functionalities were prepared, their absolute stereconfigurations were determined and their high optical purity (> 99% ee) was confirmed. Preliminary NMR study of the binding properties of the prepared multifunctional inherently chiral hosts towards (L)-phenylalaninol, (R)-mandelic acid and its TBA-salt, taken as representatives, showed small but distinct spectral changes, which were clearly different between enantiomers of calixarenes, indicating enantioselective complexation. This confirms the great potential of the developed design strategy for constructing enantiopure multifunctional hosts whose structure can be easily altered according to functionality of the chiral guest of interest.