The synthesis of some chiral lariat crown ethers and investigation of their molecular recognition properties

The enantiomeric recognition and the separation of amino compounds are amongst the main topics of Host-Guest chemistry because these compounds are basic building blocks of biological molecules. Extensive research has been carried out towards the synthesis of chiral crown ethers and the enantiomeric recognition of protonated primary amines. There is still a strong requirement for novel types of such host molecules in order to allow a proper evaluation of the chiral microenviroment of changes in each of the diastereomeric faces during the enantioselective recognition process.In this study, three novel monoaza-15-crown-5 lariat ether (1b-4b) have been synthesized in order to investigate their molecular recognition properties towards ?-amino acid ester and alkyl ammonium salts. Therefore, chiral amino alcohols 1a and 2a were synthesized by regioselective ring opening of (R)-styrene oxide and (S)-glycidyl phenyl ether with readily available (R)-3,3-dimethyl-2-butylamine in high yields. Chiral amino alcohols 3a and 4a were also synthesized with (R)-styrene oxide, (S)-glycidyl phenyl ether and 2-phenylamine in similar manner. The cyclization reaction of chiral amino alcohols 1a-4a with triethylenglycol ditosylate under high dilution closure conditions gave macrocycles 1b-4b in 30 to 48 % yields. The structures of synthesized amino alcohols and macrocycles were identified by their spectral data.Molecular recognition properties of synthesized macrocyclics 1b-4b towards alanine, phenylalanine and valine methyl ester hydrochlorides and ?-(1-naphtyl)ethylammonium perchlorates were investigated by Uv-vis titration method. It was observed that macrocycles 1b-4b formed complexes of appreciable binding constant towards all guests. Whereas the binding constants towards amino acid ester salts were 7306 ? 12969 dm3 mol-1, the lower values were obtained towards alkyl ammonium salts (5364-6423 dm3 mol-1). However, macrocycles 1b-4b exhibited low enantioselectivity towards all of protonated ammonium salts. Hosts 1b and 2b exhibited the highest enantioselectivity towards phenyl alanine salts by a KL/KD = 1.3. Hosts 1b and 2b which are bearing additionally one stereogenic center outside of macroring were not exhibited any different molecular recognition properties than 3b and 4b. It can be stated that the unexpected enantioselectivity behavior of the hosts was due to their high conformational flexibility.Key Words: Chiral monoaza lariat ethers, molecular recognition, enantioselective complexation, amiono acid esters, Uv-vis titration.