Recognition of Amino-Acid Derivatives

Inoue et al. reported that one of the enanliomers of N-(carbobenzyloxy)amino acids was extracted to a chloroform 

Entry Host Guest AAC°DL/kJ mol Solvent Temperature (K) Method Reference 

Bonar-Law reported chiral recognition of amino-acid esters by steroid-capped zinc porphyrin receptor 72 in CH2CI2 and in SDS micelle. - It showed enantioselective binding of 6.3 kJ/mol for serine in CD2CI2 and of 8.2 kJ / mol for threonine (the difference in the association free energy) at 295 K in a SDS micellar solution. Bonar-Law and Sanders reported an enantioselective binding (AAG = 3.1 kJ/mol) of octyl glucopyranoside by steroid-capped zinc porphyrin 72.  

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Konishi K., Yahara K. A novel anion-binding chiral receptor based on a metalloporphyrin with molecular asymmetry. Highly enantioselective recognition of amino acid derivatives. J Am Chem Soc 1994 116 1337-44. 

Fig. 3 (a) The 0(A (left) atropisomer and fran -a -atropisomer (right) with bound isoquinoline in the picket-fence porphyiin receptor (Ref. [29]). (b) The strapped porphyrin receptor with a rigid phenanthroline strap (Ref. [30],). (o) Chiral basket-handle receptor exhibiting a high degree of chiral recognition of amino acid derivatives (Ref [31]). 

C. Recognition of Amino-Acid Derivatives in Organic Solvents.297... 

C. RECOGNITION OF AMINO-ACID DERIVATIVES IN ORGANIC SOLVENTS... 

Recently, CSPs based on macrocyclic antibiotics such as vancomycin, teicoplanin, or ristocetin A have been introduced. These CSPs can separate many enantiomers of underivatized and derivatized amino acids in the normal and reversed-phase modes. In addition to n-n interactions, hydrogen bonding, electrostatic and hydrophobic (in the case of reversed-phase mode) interactions could help in the chiral recognition of amino acid derivatives. 

He X, Cui X, Li M et al (2009) Highly enantioselective fluorescent sensor for chiral recognition of amino acid derivatives. Tetrahedron Lett 50 5853-5856... 

Alfonso I, Buiguete MI, Galindo F et al (2009) Unraveling the moleeular recognition of amino acid derivatives by a pseudopeptidic macrocycle ESI-MS, NMR, fluOTescence, and modeling studies. J Org Chem 74 6130-6142... 

Selected relevant examples (a) Gal, A., Andreu, D., Echavarren, A. M., Prados, P. and de Mendoza, J. (1992) A Receptor for the Enantioselective Recognition of Phenylalanine and Tryptophan under Neutral Conditions, J. Am. Chem. Soc. 114, 1511-1512 (b) Konishi, K., Yahara, K., Toshishige, H., Aida, T. and Inoue, S. (1994) A Novel Anion-Binding Chiral Receptor Based on a Metalloporphyrin with Molecular A mmetry. Highly Enantioselective Recognition of Amino Acid Derivatives, J. Am. Chem. Soc. 116, 1337-1344 (c) Sessler, J. L. and Andrievsky, A. (1998) Efficient transport of aromatic amino acids by sapphyrin-lasalocid conjugates, Chem. Eur. J. 4,159-167. 

Pioneering studies by Cram and co-workers employed crown ether arrays 35a-c incorporating a 2,2 -dihydroxy-l,l -binaphthyl unit as the chiral barrier <1975PAC327>. Enhancements in the chiral recognition of amino acids were obtained by placing large substituents, at the 3,3 -positions of the binaphthyl moiety, so as to raise its steric barrier. 3,3 -Diphenyl derivative 35c is often the benchmark to which other chiral crown ethers are compared <1981JOC393>. 

Recently, a strong trend in molecular recognition is the development of molecular imprinting polymers (MIP). MIPS have been used as synthetic antibodies in immunoassays and biosensors, but also as catalysts and separation media (employed both in analysis and extraction). One of the first applications of MIPs in separations was the enantiomeric separation of amino acids derivatives. 

Codoy-Alcantar, C. Nelen, M.I. Eliseev, A.V. Yatsi-mirsky, A.K. Molecular recognition by natural macro- 25. cycles. Part II. Esterolytic activity and chiral discrimination of amino acid derivatives by the zwitterionic form... 

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

The short-end injection was also used in a paper by Perrin et al. [28]. They saw a very high chiral recognition capability of highly sulfated cyclodextrins (HS-CD). Using a test set of 27 amino acid derivatives, the application of HS-a-CD, HS-fl-CD, and HS-y-CD in a 5% w/v concentration allowed the separation of 26 compounds, of which 22 had a Rs > 2. From their experiments, a screening and optimization scheme was derived (Figure 3.3), and based on this scheme, a separation strategy was defined... 

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