Amino acid a-substituted

Stereochemical control of a reaction can also be achieved using non-chiral catalysts, when a chiral centre already exists in the reactant, as for example in the reaction of cyano- or methoxycarbonylmethyl phosphonates with 3-hydroxy-2-(S)-alkylated products are obtained with ca. 40% de of the 2(S)-3(R)-diastereoisomers [11]. Similarly, when ethyl glycine is Ar-protected with (S)-menthone, C-alkylation under soliddiquid conditions using a non-chiral catalyst (6.4.5) provides a route to chiral a-substituted amino acids with optimum enantiomeric excesses of up to 47% [12],... 

This enzyme [EC 3.1.1.29], also called peptidyl-tRNA hydrolase, catalyzes the hydrolysis of an A-substituted aminoacyl-tRNA to produce an A-substituted amino acid and tRNA. 

A chemical reaction in which the carboxyl group of an a-amino acid is replaced by an acyl group Le., an acyl-decarboxylation). In this reaction, an a-amino acid is reacted with an anhydride in the presence of pyridine and the resulting product is an A-acylated ketone. In certain instances, A-substituted amino acids will also act as reactants. 

We now take account of the specific character of the incorporation of these a-substituted amino acids into polypeptides. Enzyme inhibition by a-fluoromethyl amino acids is detailed in Chapter 7. 

Reactions of this type provide one of the major routes to the commercially important l,4-benzodiazepin-2-one system (156) via the reaction of substituted o-aminobenzoph-enones (155) with amino acid esters (68CRV747, p. 756). This synthesis allows the easy preparation of 3-substituted products by the use of readily available a-substituted amino acids, e.g. the CNS active Tranxene (156 Y = C1, Ar = Ph, R1 = CC>2H) by using aminomalonic ester. Similar reactions have been carried out using other three-atom components, e.g. 2-bromoethylamine (77MIP51800) and ketenimines (77JHC99). 

B. A. Synthesis of a-substituted / -amino acids using pseudoephedrine as a chiral auxiliary. Org. Lett. 2000, 2, 3527-3529. 

Dehydromorpholinones 4 can be used to prepare unnatural amino acids and a-substituted amino acids (Scheme 2.1).9 The phenylglycinol unit is cleaved by hydrogenolysis. 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

A variety of amino acid-like stmctures has been incorporated via directed artificial translational recoding, including a-hydroxy acids, A-substituted amino acids, and severely constrained amino acids (e.g., 1-amino-1-carboxycyclopropane), along with myriad side chains that far exceed the length and shape parameters of the canonical 20 residues. The ability to accommodate such a broad range of structures suggests that the translation machinery may have evolved to accept many other amino acids beyond the canonical 20 and that other naturally occurring co-translationally inserted amino acids remain to be discovered, as evidenced by the recent discovery of the twenty-second amino acid pyrrolysine. 

When an a-amino acid is treated with an anhydride in the presence of pyridine, the carboxyl group is replaced by an acyl group and the NH2 becomes acylated. This is called the Dakin-West reaction. The mechanism involves formation of an oxazolone. The reaction sometimes takes place on carboxylic acids even when an a amino group is not present. A number of A-substituted amino acids, RCH(NHR )COOH, give the corresponding A-alkylated products. 

The l enantiomers of a- methyl-isoleucine and a-methyl-allo-isoleucine are in fact the four diastereomers of 2-amino-2.3-dimethyl-penta-carbonic acid. The crucial result of the analysis of these a-substituted amino acids showed that their L-enantiomers each had an ee of 12.1.4% and 14.0%, respectively, similar to Murchison s (Pizzarello et al. 2006). 

A/ -substituted amino acid NCA has been applied to a similar reaction. ... 

Classification Sodium salt of a substituted amino acid Empirical CsHeNNaOs Formula HOCH2NHCH2COONa... 

An important hypothesis concerning the function of N-hydroxy-amino acids has been formulated recently by Ottenheijm 126). There are indications that the metabolism of several types of non-protein amino acids such as N-hydroxyamino acids, dehydroamino acids and a-substituted amino acids is connected with the process of oxidation of amino acids or peptides. Hence it is suggested that N-hydroxy amino acids play an important role in the biosynthesis of dehydroamino acids 18 natural antiviral, antifungal or antibacterial products (as e.g. glio-toxin) 127) and some other fungal metabolites as sporidesmine 126), as sketched in Scheme 16. 

Asymmetric Alkylation Leading to a-Substituted Amino Acid Derivatives... 

Kaptein B., Monaco V., Broxterman Q.B., Schoemaker H.E., Kamphuis J. (1995), Synthesis of dipeptides containing a-substituted amino acids their use as chiral ligands in Lewis-acid-catalyzed reactions, Recl.Trav.Chim. Pays Bas, 114, 231-238. 

Asymmetric amino acid synthesis via diastereoselective alkylation of the lithiated bis-lactim ether (derived from L-Val and Gly or Ala) by an electrophile. Subsequent acid hydrolysis liberates L-Val-OCH3 and the (7 -a-substituted amino acid ester. When the bis-lactim is generated from D-Val, the fl -enantiomer forms ... 

Studies to date indicate that transaminases are specific for L-amino acids and a-keto acids. Peptides and other derivatives of amino acids, such as amides and A -substituted amino acids, are not active. Recently it has been reported that E. coli extracts catalyze a transamination reaction between adenine and a-ketoglutaric acid. ... 

Clearly, the incorporation of a substituted amino acid into the 6-position could impose conformational rigidity on the molecule and hence, might give it a better fit into the corresponding receptor. 

Cyclic carbonates react with isocyanates in the presence of catalysts to give oxazolidi-nones with elimination of carbon dioxide The catalysts sometimes cause trimerization of the isocyanate. Carbonates derived from a-hydroxy carboxylic-, a-mercapto carboxylic and a-A-substituted amino acids react with isocyanates with elimination of carbon dioxide to give five-membered ring [3+2] adducts. ... 

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