Chiral Amine Recognition

Chiral recognition in these phases is achieved when a chiral center is introduced into the crown ether to serve as a barrier to one enantiomer of the guest amine. The chiral barrier is usually a large bulky group that selectively affects the association of one enantiomer of the amine. 

If both the ester and the amine are chiral, diastereomeric amides are formed, going in hand with recognition of both chiral entities [275]. 

The dependence of chiral recognition on the formation of the diastereomeric complex imposes constraints on the proximity of the metal binding sites, usually either an hydroxy or an amine a to a carboxyHc acid, in the analyte. Principal advantages of this technique include the abiHty to assign configuration in the absence of standards, enantioresolve non aromatic analytes, use aqueous mobile phases, acquire a stationary phase with the opposite enantioselectivity, and predict the likelihood of successful chiral resolution for a given analyte based on a weU-understood chiral recognition mechanism. 

An example for this approach is the immobilization of (5 )-(-)-a-A-(2-naph-thyl)leucine, a 7t-donating group on silica. This chiral selector exhibits excellent recognition for 3,5-dinitrobenzoyl (DNB)- and 3,5-dintroanilido (DNAn)-deriva-tives. Amines and alcohols can be derivatized with DNB- or DNAn-chloride to the esters or carbamates and separated on the CSP, as shown by Pirkle for a wide variety of compounds [27]. 

This chapter provides (i) a brief review of the chemistry involved in chiral host-chiral guest recognition involving primary amines (ii) a description of a nonchromatographic (equilibrium or bind-release based) separation process devel-... 

Chiral Recognition. The use of chiral hosts to form diastereomeric inclusion compounds was mentioned above. But in some cases it is possible for a host to form an inclusion compound with one enantiomer of a racemic guest, but not the other. This is caUed chiral recognition. One enantiomer fits into the chiral host cavity, the other does not. More often, both diastereomers are formed, but one forms more rapidly than the other, so that if the guest is removed it is already partially resolved (this is a form of kinetic resolution, see category 6). An example is use of the chiral crown ether (53) partially to resolve the racemic amine salt (54). " When an aqueous solution of 54 was... 

Zhang, X.X., Bradshaw, J.S. and Izatt, R.M. (1997) Enantiomeric recognition of amine compounds by chiral macrocyclic receptors. Chemical Reviews, 97, 3313-3361. 

Both steric and electronic factors are used for chiral recognition of saccharides by the R and S forms of S-3. A difference in PET efficiency is created by the asymmetric immobilization of the amine groups relative to the binaphthyl moiety upon 1 1 complexation of saccharides by d- or L-isomers. For instance, D-fructose is recognized by the R form of S-2 with a large fluorescence enhancement. 

For example22, separation of enantiomers of chiral molecules (amines, alcohols, amino acids) is possible by using a chiral stationary phase obtained from 10-undecenyl esters of Af-(2-naphthyl)-a-amino acids (4). Amino groups are of fundamental importance in this practical application of the chiral recognition. 

Attempting to narrow down the range of activity to a specific receptor (FoxA receptor in Yersinia enterocolitica), an additional set of chiral ferrioxamine analogs 152-155, modified at the vicinity of the terminal amine, snspected to be involved in receptor recognition was prepared . Of particular interest is the observation that 152 was utilized by the uptake system of ferrioxamine B in Yersinia enterocolitica but failed to use the ferrioxamine uptake route in Pseudomonas putida, exhibiting therefore species specificity. 

A chiral recognition was observed in aminolysis of 3-acyl-4(R)-methoxycarbonyl-l,3-thiazolidine-2-thione, a derivative of (R)-cysteine, by racemic amines to give an optically active amide [(S)-excess] and amine [(R)-excess]264). In the reaction of cyclic meso-1,3-diols with chiral N-protected phenylalanyl chlorides, Yamada et al.26S) observed the preferential formation of one of the two possible diastereomeric monoesters, which has been used for the synthesis of optically active steroids 266) and prostaglandins 267). 

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