A highly enantioselective receptor for N-protected glutamate and anomalous solvent-dependent binding properties.

Abstract

The development of enantioselective receptors continues to be a challenging endeavor for supramolecular chemists, and enantioselective recognition of biologically relevant molecules in competitive solvents is particularly demanding.[1] Although numerous receptors have been developed for dicarboxylic acids and dicarboxylates,[2] only a few enantioselective receptors for chiral dicarboxylic acids (in the neutral diprotonated form) have been described,[3] and very few examples of enantioselective receptors for chiral dicarboxylates have been reported.[4] We recently described an acyclic monothiourea receptor 1a, which bound a range of N-protected amino acid carboxylate salts with modest enantioselectivity.[5] Building on this work, we have now prepared macrocyclic receptor 2, which features two thiourea moieties flanked by carboxypyridines and separated by a chiral diamine. The receptor was designed to produce a chiral pocket for dicarboxylates by forming up to eight hydrogen-bonding interactions with the carboxylate oxygen atoms and intramolecular hydrogen bonding with the pyridine unit to help preorganize[6] the receptor (Scheme 1). Binding measurements, by NMR titration and isothermal