Unmodified Amino Acids

Several unmodified amino acids (1-7) have been used directly for the activation of substrates via the enamine mechanism. In such transformations, the chirality of amino acids induces stereoselectivity in the product formation. If a high level of enantioselectivity is attainable, such unmodified amino acid catalysts are certainly ideal due to their ready avaUabihty and economical nature. 

This type of catalyst is created by simply introducing protection to the functional group at the side chain of amino acids (8-11). In particular, a L-threonine core has been shown to be ejctremely powerfijl in asymmetric induction. Hydrophobic protective groups were often introduced, and it is believed that hydrophobic effects might play important roles for reactions performed in aqueous medium. 

Quite recently, chiral diamines have been recognized as effective catalysts in asymmetric catalysis [16]. Utilizing primary amino acid structural scaffolds, several novel diamine catalysts have been developed, which can be classified as primarysecondary diamines (12-14) and primary-tertiary diamines (15-18). Notably, such diamines are often used in combination with Bronsted acid additives for effective activation of substrates. 

---

Fixed modifications are modifications to specific amino acids that are considered to be complete—i.e., every occurrence of the amino acid in the sequence is assumed to carry the modification, and the unmodified amino acid is not considered. Variable modifications, on the other hand, are incomplete, and therefore both the modified and unmodified amino acid are considered in the search. In the example discussed above, the reduction/alkylation should result in complete carbamidomethylation of all cysteine residues thus, Carbamidomethyl (C) was chosen as a fixed modification, whereas methionine oxidation, a common artifac-tual modification that is usually incomplete, was selected as a variable modification The use of multiple variable modifications will greatly reduce the significance of any match and should therefore be used with caution. 

The DNP-amino acids, after separation into individual spots on the chromatographic plate, can be eluted from the scraped off area by adding 4 ml of water to the material in a small tube. The tube is heated at 50° in a water bath for 15 minutes and centrifuged to clear the solution. The color is read against known standards at 360 nm. Direct estimation of DNP-, PTH-, and DANS-amino acids separated on the thin-layer plate can be performed by fluorescence and fluorescence quenching techniques (P8). It is also possible to convert unmodified amino acids, separated on a silica gel G chromatographic plate, into DNP-amino acids by in situ conversion as was described in Section 4.7.18. The DNP-derivatives can then be developed in the second dimension and the spots analyzed quantitatively. 

Cyclamides, main class of cyanobacterial peptides. As verified in nostocyclamide, a typical peptide of this family, thia-zole/oxazole units occur in alternation with unmodified amino acids forming a cyclic 6-peptide. The first peptides of this class are the bistratamides [A. K. Todorova et al., Org. Chem. 1995, 60, 7891 M. Welker, H. 

ABSTRACT. The copper(n) complexes of p-cyclodextrins functionalized with aliphatic or pseudoaromatic amines were used for the chiral recognition of unmodified amino acids. Molecular recognition, assisted by non-covalent interactions, was proved by means of thermodynamic and spectroscopic (c.d., e.p.r. and fluorescence) measurements. A cis-disposition of amino groups seems to assist enantiomeric selectivity. The copper(II)-p-cyclodextrin complexes can be used as mobile phase additives in HPLC to separate enantiomeric mixtures of unmodified aromatic amino acids. 

Bearing this in mind, we designed and synthesized a number of P-CD derivatives [27-34] which could i) bind copper(II) forming a multisite recognition system ii) show thermodynamic stereoselectivity in copper(II) ternary complexes iii) perform chiral separation of unmodified amino acid enantiomers. Among the monofunctionalized P-CD derivatives, only those functionalized in position 6 with diamines show chiral molecular recognition [29,32,35-37]. On the contrary, the P-CDs both functionalized in position 3 and those where a triamine was attached to the narrower rim of the toroid do not act as chiral receptors. 2-(aminomethyl)pyridine, histamine and NH3 molecules were used to obtain the three isomers of P-CDs (Figure 3), but only the A,BCD-NH2 molecule, coordinated to the copper(II) ion, is seen to have enatioselective effects on aromatic amino acids [38]. 

This approach is particularly interesting because it requires very low concentrations of the sensor, and it allows one to perform enantioselective sensing in water on very low quantity of unmodified amino acids, which are insoluble in most organic solvents used in the vast majority of sensory systems described in the literature. 

Corradini R, Paganuzzi C, Marchelli R et al (2005) Fast parallel cmantiomeric analysis of unmodified amino acids with fluorescent P-cyclodextiins. J Mater Chem 15 2741-2746... 

---