D-a-Amino acids

D-a-Amino acids. Rapoport et al. have developed a general synthesis of unnatural D-a-amino acids with L-serine as the chiral eduet. The method involves aminoacylation 

D)-a-amino-acids (549) (Scheme 43). An alternative route from 

D-Asparagine (D-a -amino acid) From I-Asparagine racemization Sweet 

D-Glutamine (D-a-amino acid) From I-Glutamine racemization Sweet 

Bender, D. A. Amino Acid Metabolism, 2nd ed. New York John Wiley, 1985. [A general treatment of the topic, with a particularly good section on tryptophan metabolism.] 

Bender, D. A., Amino Acid Metabolism. New York John Wiley and Sons, 1985. 

D-Phenylalanine (D-a-amino acid) From I-Phenylalanine racemization Sweet 

The L-a-amino acid moiety of ACM is not absolutely required, since other aminocyclohexadienes with a D-a-amino acid or without functionality in the side chain are also efficient inhibitors. In all cases, the rate of inactivation is higher with the cis than with the trans isomers." Very similar results were obtained with the M. tuberculosis enzyme that was inhibited by ACM and another analog (14) irreversibly, with the kinetic 

D-a amino acid i Figure 1.3 Structures of a-amino acids the monomeric building blocks of proteins. 

Alkylation of protected glycine derivatives is one method of a-amino acid synthesis (75). Asymmetric synthesis of a D-a-amino acid from a protected glycine derivative by using a phase-transfer catalyst derived from the cinchona alkaloids (8) has been reported (76). 

Hydrolysis of the azlactone leads to the acylaminooinnamic acid the latter may be be reduced catal3rtlcally (Adams PtOj catalyst 40 lb. p.s.i.) and then hydrolysed by hydrochloric acid to the amino acid. Alternatively, the azlactone (say, of a-benzylaminocinnamic acid) may undergo reduction and cleavage with phosphorus, hydriodic acid and acetic anhydride directly to the a-amino acid (d/ p phenylalanine). 

It IS understood that a amino acids occur as their l stereo isomers unless otherwise indicated The d notation is explicitly shown when a D amino acid is present and a racemic amino acid is identified by the prefix dl 

Boesten, W.H.J. and Cals, M.J.H. 1987. Process for the enzymatic hydrolysis of d-a-amino-acid amides. US Patent 4 705-52. 

Figure 19-26. Production of L-and D-a-amino acids by kinetic resolution of a-amino acids amides (DSM).

In many cases only the racemic mixtures of a-amino acids can be obtained through chemical synthesis. Therefore, optical resolution (42) is indispensable to get the optically active L- or D-forms in the production of expensive or uncommon amino acids. The optical resolution of amino acids can be done in two general ways physical or chemical methods which apply the stereospecific properties of amino acids, and biological or enzymatic methods which are based on the characteristic behavior of amino acids in living cells in the presence of enzymes. 

Fig. 9.6 Mirror image behaviour of enantiomeric molecules. The left-handed L-a-amino acid is converted to the right-handed D-a-amino acid by reflection 

Figure 22-6. The hydrogen bond association of the L-diamide phase in its antiparaUel P-sheet conformation with (A) N-TFA-L-a-amino acid alkyl ester and (B) A-TFA-d-a-amino acid alkyl ester. (Reprinted from reference 35, with permission.)

The products of the conjugate addition of (f )-4-phenyl-2-oxazolidinone to nitroalkenes are converted into D-a-amino acids with high enantiomeric purity (Eq. 4.30).36 

Azumamide E is a cyclotetrapeptide natural product isolated from marine sponge Mycale izuensis. Like most cyclopeptide HDAC inhibitors, these compounds contain D-a-amino acids (D-Phe, D-Tyr, D-Ala, D-Val) which relieve ring strain (Fig. 7). However, they are unique from other natural cyclopeptide HDAC inhibitors with a retroenantio arrangement. 

Naturally air-fused DKPs are thermodynamically more stable, compared with their trawr-fused counterparts. This seems logical considering their biosynthetic origin, usually from two proteinogenic L-a-amino acids. Some other cis- and rntwr-functional DKPs are derived from nonproteinogenic D-a-amino acids. Naturally 

Addition of various organometalic reagents to chiral nitrones, derived from L-erythrulose, proceeds with variable diastereoselectivity, depending on Lewis acids as additives. ZnBr2 facilitates the attack at the Si face of the C=N bond, whereas Et2AlCl makes the attack at the Re face more preferable. The obtained adducts can be transformed into derivatives of /V - h y d r o x y - u. u - d i s u b s t i t u t e d -a-amino acids, with their further conversion into a,a-disubstituted a-amino acids (193, 202). 

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