Amino-acid derivatives chiral recognition

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... 

Since Pasteur separated crystalline sodium ammonium tartrate manually in 1848, many researchers have worked on the subject of enantiomeric separation. In 1939 Henderson and Rule fully separated derivatives of camphor by column chromatography using lactose as a stationary phase material [1]. Gil-Av et al. [2] were able to separate amino acid derivatives on a polysiloxane-based stationary phase by gas chromatography (GC) in 1966. Since then many approaches for a successful distinction between enantiomers have been developed for capillary GC and liquid chromatography [3]. It is still a current topic for researchers searching for chiral separation with SciFinder [4] results in 812 hits and searching for chiral recognition leads to 285 hits for the year 2003 only. 

Aminolyses of rac-14a were tried with several types of amines, i.e., oc-amino acid derivatives, ) -amino alcohols, and 3-amino-) -lactams (Scheme 4). The results are as follows. In the case of a-amino acid derivatives, the (S)-enantiomer reacted with (4/ )-HDMCTT (14a) preferentially and vice versa [(/ )-enantiomer + (4S)-HDMCTT], which was in good agreement with the chiral recognition of racemic amine with (4/ )-AMCTT (14). In the case of ) -amino alcohol derivatives, the (S)-enantiomer showed a preferential reactivity to (4S)-HDMCTT, resulting in the recovery of (4/ )-HDMCTT. In the case of 3-amino-) -lactams, (R)-penam-, (R)-cephem-, and (S)-oxacephem derivatives all showed a preferential reactivity to (4S)-HDMCTT (R)-oxacephem derivatives reacted predominantly with (4/ )-HDMCTT. 

Chiral recognition of a-amino acid derivatives with a homooxacalix[3]arene construction of a pseudo-C2-symmetrical compound from a C3-symmetrical macrocycle, K. Araki, K. Inada and S. Shinkai, Angew. Chem. Int. Ed. Engl., 1996, 35, 72. 

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. 

Susan, EB, HC John, FL Stephen and R Daniel (1991). Coghlan and Christopher J. Easton. Chiral molecular recognition A 19F nuclear magnetic resonance study of the diastereoisomer inclusion complexes formed between fluorinated amino acid derivatives and a-cyclodextrin in aqueous solution. Journal of the Chemical Society, Faraday Transactions, 87,2699-2703. 

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]). 

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... 

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. 

Commercially available silica gel plates coated with acid or basic chiral selectors [o-galacturonic acid, l-(- -)-tartaric acid, L-lactic acid, (-)-brucine] were used for the separation of racemic ephedrine, atropine, neutral amino acids, and their 3-phenyl-2-thiohydantoins (PTH) derivatives. The use of amino acids as chiral selectors involved further possibilities of enantiomer separation owing to the simultaneous presence of basic and acidic groups. In fact, L-aspartic acid, L-lysine, L-histidine, L-arginine, and L-ser-ine resolved racemic alkaloids, (3-blockers, profens, some amino acids, and their Dns derivatives. Macrocyclic antibiotics [i.e., (-)-erythromycin and (-)-vancomycin] were also used as chiral agents for the separation of enantiomeric DNs amino acids. The mechanisms of chiral recognition was investigated by Aboul-Enein, El-Awady, and Heard they hypothesized that the formation of... 

---