Novel chiral imidazole cyclophane receptors were synthesized by highly selective N-alkylation of the imidazolyl 1N-position of the bridged histidine diester 2 with the dibromide in the presence of NaH; these receptors exhibit good chiral recognition toward the enantiomers of L-and D-amino acid derivatives (up to K D /K L = 3.52, DDG 0 = 23.11 kJ mol 21 ) in CHCl 3 at 25.0°C.Molecular recognition between molecules is one of the most fundamental processes in biochemical systems. The study of synthetic model systems could contribute to the understanding of these processes and, at the same time, offer new perspectives for the development of pharmaceuticals, enantiomer-selective sensors, catalysts and molecular devices. 1 One area that has proven especially challenging is the creation of enantioselective artificial receptors. 2 Cyclophanes have gained considerable interest because of their potential applications in artificial enzymes, host-guest complexes, molecular self-assembly, selective catalysis and material science. 3 A variety of cyclophanes with novel structures and properties have been reported. However, inspecting the impressively long list, examples dealing with histidine are quite rare. 4 Imidazole and histidine derivatives are generally considered to be difficult to prepare, so this makes the development of imidazole-containing receptors much more challenging. Our interest has been focused on the synthesis of imidazolium and imidazole cyclophanes. 5 Recent work aimed to synthesize chiral macrocyclic tetraoxo polyamines containing two functional imidazole arms that are oriented in an anti fashion, and to develop a convenient and efficient method for the synthesis of bridged histidine derivatives. 6 On the basis of this method, we herein report the synthesis of novel chiral imidazole cyclophane receptors from L-histidine (Scheme 1), and their enantioselective recognition for amino acid methyl esters. To our knowledge, this is the first example of a chiral imidazole cyclophane from L-histidine as a chiral recognition receptor.We have previously synthesized chiral macrocyclic tetraoxo polyamines containing two functional imidazole arms via aminolysis of the dihistidine dimethyl esters 2 with commerically available polyamines. 6 The key intermediate 2 was directly used without protection of the imidazole ring. Herein four novel chiral imidazole cyclophanes 3-6 were obtained by highly selective N-alkylation of the imidazolyl 1N-position of 2 with the corresponding dibromides in the presence of a slight excess of NaH in DMF under dry and oxygen-free conditions at 25-0°C. The reaction conditions have a significant influence on the macrocyclization because the bridged compound 2 possesses several active functional groups, and the N-alkylation of imidazole groups usually leads to serious side reactions such as the quaternization reaction of imidazole and the elimination reaction of halides. 5,7 To minimize these side reactions and competitive reactions between the imidazolyl 1N-position and the NH of CONH, 8 th...
Two kinds of novel chiral molecular tweezers containing imidazoliums were synthesized from L-alanine, L-phenylalanine, and L-glutamic acid. They are constructed by the chiral imidazolium pincers and two different spacers which are 1,3-bis (bromomethyl)benzene and 2,6-bis(bromomethyl)pyridine, respectively. The enantioselective recognition of L- and D-amino acid derivatives by these molecular tweezers was investigated by UV spectroscopic titration experiments and good enantioselectivities were obtained, which are highly sensitive to whether the spacer has the binding site and the pincers has the other aromatic rings besides imidazolium ring. The host molecular 3b.2PF6- showed remarkable enantioselectivity for N-Boc protected histidine methyl ester, affording K(L)/K(D) of 5.10.
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