Amino acids, chiral sensing

Corradini R, Paganuzzi C, Marchelli R et al (2003) Design and synthesis of fluorescent (3-cyclodextrins for the enantioselective sensing of a-amino acids. Chirality 15 S30-S39... 

Hsu s group in Taiwan have developed a procedure for the synthesis of (Y)-2-amino-4-phenylbutanoic acid, the phenylalanine homologue with one additional methylene group. Hydantoinase and L-A-carbamoylase genes have been cloned from different Bacillus species and overexpressed in E. coli. Both the R- and the 5-enantiomers were cleaved by the hydantoinase, but only the 5-form of the A-carbamoyl amino acid was hydrolyzed by the second enzyme. The reactions could be run in a single pot, with successive addition of the two enzymes, and were successful in the sense of giving a product of high chiral purity. However, the yield was... 

From an industrial chemist s point of view the use of proline, phenylalanine, valine, and other commercially available amino acids, is fine. To date, however, tert.-(S)-leucine is still an exotic compound. It should also be noted that the recycling of the chiral amino acid moiety is of importance for possible technical processes. On the other hand, the recovery of the chiral auxiliary sometimes does not make sense, especially in syntheses which the require the use of stochiometric amounts of expensive reagents, e.g. LDA. 

For example, our ability to taste and smell is regulated by chiral molecules in our mouths and noses that act as receptors to sense foreign substances. We can anticipate, then, that enantiomers may interact differently with the receptor molecules and induce different sensations. This appears to be the case. The two enantiomers of the amino acid, leucine, for example, have different tastes—one is bitter, whereas the other is sweet. Enantiomers also can smell different, as is known from the odors of the two carvones. One has the odor of caraway and the other of spearmint. 

The design of the peptide implies that interaction of the catalyst with its substrate relies heavily on hydrogen bonding. Initial studies indeed revealed that, in particular, N-acyl amino alcohols such as 25 and ent-25 were efficiently differentiated whereas both enantiomers of l-(l-naphthyl)ethanol were acetylated at identical rates [28]. Catalyst 23b, shown in Scheme 12.12, was the most efficient from a series of ten peptides. For best performance, proper matching of the sense of chirality of all three chiral amino acids is necessary, and the type of amino acid present at the carbon terminus enables further tuning (for example, L-Phe was found to be better than, e.g., L-Val, selectivity factor 21) [29]. 

Marchelli used the copper(II) complex of histamine-functionalized P-cy-clodextrin for chiral recognition and separation of amino acids [27]. The best results were obtained for aromatic amino acids (Trp). Enantioselective sensing of amino acids by copper(II) complexes of phenylalanine-based fluorescent P-cyclodextrin has been recently published by the same author [28, 29]. The host containing a metal-binding site and a dansyl fluorophore was shown to form copper(II) complexes with fluorescence quenching. Addition of d- or L-amino acids induced a switch on of the fluorescence, which was enantioselective for Pro, Phe, and Trp. This effect was used for the determination of the optical purity of proline. 

An aromatic Claisen rearrangement has been used as a key step in a total synthesis of racemic heliannuols C and E.18 A formal synthesis of (-)-perhydrohistrionicotoxin has used Claisen rearrangement of an amino acid ester enolate as the key step, in which almost total chirality transfer was observed from (S, )-oct-3-en-2-ol in the sense predicted by a chair-shaped transition state with chelation control of enolate geometry.19 Treatment of 1-(cyclohex-l-enyl)-6-methoxy-2-propargylindanol derivatives with base... 

The Merck group has applied the electrophilic amination using lithium terf-butyl N-(tosyloxy)carbamate 9a to the chiral amide derived from (lS,2/ )-cw-amino-indanol [10] (Scheme 4). Treatment of 10 with n-Buli in THF at -78 °C gave the lithium enolate which was reacted with CuCN. The resulting amide cuprate was allowed to react with 9a. The authors found that a single diastereomer of a-Boc-protected amino amide 11 was formed. The sense of asymmetric induction observed was consistent with preferential approach of 9a from the least hindered face of the enolate. The removal of the chiral auxiliary with refluxing 6N HC1 afforded a-amino acids 12 in good yields and optical purities. 

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