Glutamic acid asymmetric synthesis

Ail extremely useful method for the asymmetric synthesis of substituted amino acids, in particular glutamic acids, is based on optically active bislactim ethers of cyclodipeptides. The lithium etiolates of bislactim ethers (which are prepared easily from amino acids) undergo 1,4-addition to various a,/ -unsaturated esters to give -substituted 2,5-dihydropyrazine-propanoates203-205 with high diastereofacial selectivity, ratio (R/S) > 140-200 1. 

That chiral molecules can be produced in a CPL field, either from achiral precursors by photo-activated synthesis or by preferential chiral photodestruction of a racemic mixture, is now well demonstrated and has been reviewed. [46] In all cases currently known, however, such processes have proved very inefficient. For example, asymmetric photochemical ring-closures of achiral helicene precursors induced by CPL have produced only about 0.2% e.e. in the products. Likewise, the CPL-induced photolysis of racemic camphor produced about 20 % e.e., but only after 99% photodestruction, and photolysis of D.L-glutamic acid produced only 0.22 % e.e. after 52 % photodecomposition. [71]... 

Stereoselective alkylation with aliphatic bromides and iodides of the Schiff bases of tert-butyl glycinate with (—)-(15,25,55)-2-hydroxypinan-3-one or (+)-(lR,2R,5R)-2-hydroxy-pinan-3-one 150 was reported to produce lipidated amino acids as d- and L-enantiomers in 80 to over 90% ee. 151 Similarly, the asymmetric synthesis of a derivative of arachidonic acid (4) has also been reported. The pure enantiomer was obtained via regioselective functionalization of a chirally pure glutamic acid. 152 ... 

Thus, (2R)-pumiliotoxin C (214) has been prepared from (R)-norvaline (212). The asymmetric center in the triene (213) controls the configuration at three carbon atoms 210). a-Kainic acid, isolated from the algae Digena simplex and Centrocerus clavulatum, was prepared by total synthesis. Its enantioselective synthesis involved a stereocon trolled intramolecular cycloaddition of a (S)-glutamic acid211). Asymmetric cycloadditions also play a decisive role in the synthesis of chiral cytochalasins. In this case 212> the primary chiral information was carried by (S)-alanine and (S)-phenylalanine, respectively. 

Recent developments regarding the utility of chiral amino acids in asymmetric synthesis of natural products were reported. Examples of such syntheses are the preparation of carbohydrates from (S)-glutamic acid 257), (S)-alanine 258), or (S)-threonine 259), and syntheses of alkaloids 260), terpenes 26I), peptide 262) derivatives, and toxines 263>. 

The synthesis of substituted glutamic acid analogues has been pursued by many routest94-106 using asymmetric alkylation, Simmons-Smith reactions, Diels-Alder reactions, and nickel complexes of glycine or alanine equivalents. 

Scheme 19 Asymmetric Synthesis of y-Substituted Glutamic Acid Derivatives via a Glutamic Acid y-Enolate...

Scheme 21 Asymmetric Synthesis of a /-Substituted Glutamic Acid from Pyroglutamic Acid[951...

The Diels-Alder reaction can be used for asymmetric synthesis of p,y-disubstituted glutamic acids.[98] Fully protected dehydroglutaminol 63 serves as a dienophile and, after a series of deprotection and oxidation of the Diels-Alder reaction product, disubstituted glutamic acids 68A and 68B (Scheme 22) can be obtained. 

Scheme 22 Asymmetric Synthesis of 3,y-Disubstituted Glutamic Acids[981...

Scheme 24 Synthesis of a y,y-Disubstituted Glutamic Acid via an Asymmetric Simmons-Smith Reaction 97-1081...

Scheme 8.7 Taddol-catalyzed asymmetric synthesis of y-methyl glutamic acid 15.

The synthesis of a-amino acids has been carried out from a-keto acids by reductive aminadon using a platinum or palladium catalyst, mimicking their biosynthesis. Thus alanine, leucine, phenylalanine, " aspartic acid and glutamic acid - have been synthesized by reductive amination. When an optically active primary amine is used, asymmetric induction can proceed in the course of the reductive amination. 

In the laboratory of D. Ma, the asymmetric synthesis of several metabotropic glutamate receptor antagonists derived from a-alkylated phenylglycines was undertaken. The preparation of (S)-1-aminoindan-1,5-dicarboxylic acid (AIDA) started with the Perkin reaction of 3-bromobenzaldehyde and malonic acid. The resulting ( )-cinnamic acid derivative was hydrogenated and the following intramolecular Friedel-Crafts acylation afforded the corresponding indanone, which was then converted to (S)-AIDA. 

Scheme 11.17 Asymmetric synthesis of (2S)-a-(hydroxymethyl)glutamic acid.

Groth, U., Richter, L., and Schollkopf, U., Asymmetric synthesis of enantiomerically pure phosphonic analogues of glutamic acid and proline, Tetrahedron, 48, 117, 1992. 

Schollkopf, U., Pettig, D., Busse, U., Egert, E., and Dyrbusch, M., Asymmetric synthesis via heterocyclic intermediates. Part 30. Asymmetric synthesis of glutamic acids and derivatives thereof by the bislactim-ether method. Michael-addition of methyl 2-alkenoates to the hthiated bislactim-ether of cyclo-(L-Val-Gly), Synthesis, 737, 1986. 

Table II shows solvent effects in the asymmetric synthesis of alanine from pyruvic acid and (S)-a-methylbenzylamine( ). The optical purity of alanine decreases with increasing polarity of the solvent. In the case of the asymmetric synthesis of glutamic acid from a-keto glutaric acid and (S)-a-methylbenzylcimine, the configuration of the resulting glutamic acid was actually inverted by the use of polar solvents. The substrate appears to interact with the catalyst more strongly in a less polar than in a more polar solvent. Thus, the population of the chelated substrate is...

Gamer P (1984) Stereocontrolled addition to a p aldic acid equivalent an asymmetric synthesis of threo-p-hydroxy-L-glutamic acid. Tetrahedrrai Lett 25 5855-5858... 

Gamer P (1984) Stereocontrolled Addition to a Penaldic Acid Equivalent an Asymmetric Synthesis of Threo-pi-hydroxy-D-glutamic Acid. Tetrahedron Lett 25 5855... 

Asymmetric induction using a transition metal complex (67), use of a carbohydrate template (68), and use of the chiral lactone 49 (69) or ester 50 (70) have all given effective syntheses of stereospecifically labeled samples of glycine. A further synthesis by Santaniello etal. (71, 72) has used glutamate decarboxylase to prepare labeled samples of y-aminobutyric acid 51 (Scheme 16). On cyclization, protection, and oxidation, these gave the labeled enamides 55, which were degraded to the labeled samples of glycine 23 (71, 72). 

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