Amino acids azide-functionalized

It is not only the activity that can be altered by incorporation of noncoded amino acids. Introduction of structures possessing certain chemical functions leads to the possibility of highly regioselective modification of enzymes. For example, selective enzymatic modification of cystein residues with compounds containing azide groups has led to the preparation of enzymes that could be selectively immobilized using click chemistry methods [99]. 

Enantiomerically pure 4,5,6-trihydroxy-norleucins (for instance 325) were obtained (197) from the hex-2-enono-1,4-lactone-2-mesylates (such as 152). These butenolides were stereoselectively hydrogenated to afford, upon treatment with sodium azide, the C-2-inverted derivatives, such as 324. Reduction of the azide function and hydrolysis of the acetal group gave the amino acids (namely 325), which were converted into lactones in acid media. 

Nonbranched amino acids substituted by a fluoroalkyl chain on a carbon distant at least one methylene from the amino acid function have been prepared as racemates by various methods." Under nonracemic form, co-perfluoroalkyl norvaline and norleucine (Rf = C2F5 or more) have been prepared by bromination of an anion of a fluorinated chiral oxazolidinone (derived from RfCH2CH2C02H). Substitution of the bromine atom by an azide and subsequent reduction yield the desired amino acids (Figure 5.10)." ... 

The application of the procedure to azides containing other functional groups has also been described. Diamines (from dicarboxylic acids), arylha loamines, and nitroarylamines have been successfully prepared, whereas certain groups like the double bond, hydroxyl, carbonyl, and amino often cause the formation of products other than the anticipated amine. For the synthesis of a-amino acids, the readily accessible alkylcyanoacetic esters may be employed as starting materials. Their azides rearrange to cyano isocyanates, which can be easily hydrolyzed. ... 

Peptide synthesis. In the above-mentioned synthesis of urethanes the carboxylic acid azide may be the intermediate, and this possibility prompted the Japanese chemists to investigate the usefulness of diphcnylphosphoryl azide in peptide synthesis. Indeed the reagent allows coupling of acylamino acids or peptides with amino acid esters or peptide esters in the presence of a base in high yield and with practically no racemiza-tion. The new method is compatible with various functional groups. 

A second approach relies on the traceless Staudinger ligation between an appropriately functionalized phosphine and an azide to produce a new amide bond [54]. This method has found extensive utility in the labeling of peptides and proteins [215]. Importantly, this method has also been used for the construction of native iV-linked glycans through the reaction between a glycosyl azide and a phosphine containing amino acid [216,217]. 

Asymmetric dihydroxylation of trifluoromethylalkenes is also useful for construction of enantio-enriched trifluoromethylated diols usable for trifluoromethylated amino acids with chiral hydroxyl group. Thus, Sharpless AD reaction of 16 provides diol 17 with excellent enantioselectivity. Regioselective and stereospecific replacement of the sulfonate moiety in 18 with azide ion enables the introduction of nitrogen functionality. A series of well-known chemical transformation of 19 leads to 4,4,4-trifluorothreonine 20 (see Scheme 9.6) [16]. Dehydroxylative-hydrogenation of 21 by radical reaction via thiocarbonate and subsequent chemical transformation synthesize enantio-enriched (S)-2-amino-4,4,4-trifluoro-butanoic acid 22 [16]. Both enantiomers of 20 and 22 were prepared in a similar manner from (2R,3S)-diol of 17. 

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