Aromatic amino acids, nonnatural

The adaptability of E. coli ribosome has been investigated by using puromycin analogs that carry a variety of nonnatural amino acids [35], Since puromycin is known to bind to the ribosomal A site without assistance of EF-Tu, the extent of the inhibition of translation by the puromycin analogs can be a direct measure of the adaptability of the A site to a variety of nonnatural amino acids. The inhibition efficiency indicated that some aromatic amino acids that carry widely expanded side groups, like 9-anthrylalanine and 1-pyrenylalanine, are... 

K. Takai, S. Yokoyama, Adaptability of nonnatural aromatic amino acids to the active center of E. Coli ribosomal A site, FEBS Lett. 1993, 335, 47-50. 

We have been studying model polypeptide systems with an a-helical main chain in which a variety of nonnatural aromatic amino acids are incorporated [27-32]. Similar studies on polypeptides carrying aromatic amino acids have been reported from other laboratories [33-42]. The polypeptide systems have the following unique characteristics ... 

Figure 1. List of nonnatural aromatic amino acids that are available in optically pure form.

Aminomethylation Reaction. The Hf(OTf)4-dopedMe3SiCl system was used as Lewis acid to catalyze the aminomethylation of electron-rich aromatic compounds. Suitable arenes include indoles, furans, pyrroles, thiophenes, and anilines, with new t)q)es of iV,0-acetals having a variety of functional groups, such as cyano, ester, bis(trimethylsilyl)amino, diallylamino, and cyclic amino moieties. This method allowed for the facile synthesis of nonnatural aromatic amino acid derivatives (eq 1). 4 Aminomethylation using a A, 0-acetal with a bis(trimethylsilyl)amino group was particularly successful in the direct preparation of a N-unsubstituted a-indolylglycine derivative, which required only a standard aqueous workup as the deprotective step. ... 

Parmar et al have developed a method for resolving racemic mixtures of a variety of natural and nonnatural amino acids using the ethyl ester of the amino acid protected at the amino position hy the formation of a Schiff base with an aromatic aldehyde such as /)-chlorobenzaldehyde. Both chymotrypsin and Lip such as porcine Lip gave good yields of the L-amino acid which precipitates out of solution as the amino acid ester released from the imine is cleaved by the hydrolase. 

Alkynes have also been used with cesium acetate both for alkynylation and in the synthesis of p)ridines and isoquinolines.The alkynylation of aromatics was promoted by the use of 8-aminoquinoline as a directing group. However, cesium acetate was used in stoichiometric amount in addition to palladium acetate (eq 5). Other insertion reactions have been performed where cesium acetate was used as an additive for nonnatural amino acid synthesis via the addition of a phenyl group during the synthetic route. Also, iodination with palladium acetate and am-ination with a rhodium complex have been successful with cesium acetate as a base. 

Hohsaka, T, Daisuke, K., Ashizuka, Y., Murakami, H., and Sisido, M., Efficient incorporation of nonnatural amino acids with large aromatic groups into streptavidin in in vitro protein synthesizing systems,/. Am. Chem. Soc., 121,34,1999. 

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