Enantioselective recognition amines

Figure 23 The preparation of enantioselective MIPs, imprinted with L-menthol 40 by ringopening metathesis pol mierization (ROMP). A copolymer of dicyclopentadiene 39 and the template monomer 41 was prepared by treatment with Grubb s catalyst. Template removal by treatment with an amine resulted in polymers capable of enantioselective recognition of 40 (adapted from Ref. 33).

Pischel U, Abad S, Miranda MA (2003) Stereoselective fluorescence quenching by photoin-duced electron transfer in naphthalene-amine dyads. Chem Commun 1088-1089 Xu M H, Lin J, Hu Q et al (2002) Fluorescent sensors for the enantioselective recognition of mandeUc acid signal amplification by dendritic branching. J Am Chem Soc 124 14239-14246... 

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. 

The same author has reported chiral recognition of a-amino acids by native, anionic, and cationic a- and (3-cyclodextrins [17]. Both carboxylates and amines (monosubstituted as well as hexa- and heptasubstituted) were included in this study. The best results obtained were those from a combination of (S)- and (P)-AcTrp complexed by per-NH -[3-cyclodextrin with K=2,310 and 1,420 (1/mol). In the detailed study of chiral recognition of substituted phenyl-acetic acid derivatives by aminated cyclodextrins, these were found to be again only modest with respect to the enantioselection attained [18]. 

Methods for catalytic asymmetric syn dihydroxylation have been developed that significantly extend the synthetic utility of dihydroxylation. K. B. Sharpless (The Scripps Research Institute) and co-workers discovered that addition of a chiral amine to the oxidizing mixture leads to enantioselective catalytic syn dihydroxylation. Asymmetric dihydroxylation has become an important and widely used tool in the synthesis of complex organic molecules. In recognition of this and other advances in asymmetric oxidation procedures developed by his group (Section 11.13), Sharpless was awarded half of the 2001 Nobel... 

Table 2 shows that the derivation of the amine group of amino acids can improve chiral recognition, e.g., the enantioselectivity factors of alanine are 1.8 and 2.7 on teicoplanin and TAG CSPs they become 13 and 3.6, respectively, upon derivati-zation of the amine group forming A-benzoyl alanine (Table 2). Enantioselectivity enhancement is very often obtained by N-derivatization of amino acids [14, 16]. Such enantiorecognition enhancement is not an absolute rule as shown by iV-benzoyl phenylalanine in Table 2. The phenylalanine enantioselectivity factors jumps from 1.5 (native form, Rs = 3.1) to 4.4 (N-benzoylated form, Rs = 11.4) on teicoplanin CSP. It decreases from 3.7 (native form, Rs = 13.7) down to 1.5 Rs = 2.6) after N-benzoylation on the TAG CSP. There is a clear steric effect due to the attached benzoyl group very beneficial for enantiorecognition on teicoplanin CSP and detrimental when the TAG CSP is used.

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