Glutamic acid derivative

Glutamic acid and its derivatives have been found in several microorganisms. The common edible mushroom, Agaricus bisporus, contains y-L-glutaminyl-4-hydroxybenzene (3.46) which is formed from 4-aminophenol and glutamic acid. This metabolite is readily hydroxylated to y-L-glutaminyl-3,4-dihydroxybenzene and oxidized to the 3,4-benzoquinone. This ort/zo-quinone decomposes to an iminoquinone, 2-hydroxy-4-iminocyclohexa-2,5-dieneone (3.47), which imparts a red colour to some mushrooms. 

Agaratine (3.48) is another glutaminic acid derivative that is found in Agaricus bisporus, where it is present to the extent of 0.1-0.3% dry weight. This metabolite has attracted interest because it may be hydrolyzed enzymatically to 

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I.5.2.4.I.2.3. Glutamic Acid Derivatives via Enolate Additions to a,/l-Unsaturated Esters... 

The addition of a-amino-substituted lithium enolates to a,/ -unsaturated esters is a diastereoselective route to syn- or anti-glutamic acid derivatives and also to fratw-substituted 5-oxo-2-pyrrolidinecarboxylates. 

Diastereoselective preparation of a-alkyl-a-amino acids is also possible using chiral Schiff base nickel(II) complexes of a-amino acids as Michael donors. The synthetic route to glutamic acid derivatives consists of the addition of the nickel(II) complex of the imine derived from (.S )-,V-[2-(phenylcarbonyl)phenyl]-l-benzyl-2-pyrrolidinecarboxamide and glycine to various activated olefins, i.e., 2-propenal, 3-phenyl-2-propenal and a,(f-unsaturated esters93- A... 

A related stereoselective route to glutamic acid derivatives consists of the addition of the nickel complex 5 to various activated olefins, i.e., 2-propenonitrile, 2-propenal and a,/ -unsaturated esters. 

Shimokuri T, Kaneko T, Serizawa T et al (2004) Preparation and thermosensitivity of naturally occurring polypeptide poly(y-glutamic acid) derivatives modified by alkyl groups. Macromol Biosci 4 407-411... 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

The main lines of this approach were later embodied in an enantioselective synthesis of (—)-a-allokainic acid (Scheme 34) (179). The sole stereo center of die ene reaction starting material was derived from a glutamic acid derivative (132) to avoid loss of optical activity via double bond migration (see Scheme 33), the a acid function of kainic acid had to be reduced before the pyrolysis step... 

G4. Gerrard, J. W., Marko, A. M., and Buchan, D., Glutamic acid derivatives in juvenile and adult celiac disease, 1. Plasma glutamic acid levels after a gliadin tolerance test. Can. Med. Assoc. J. 83, 1321-1323 (1960). 

Baggiolini et al.216) have succeeded in synthesizing the vitamin d-bioiin from (RR)-cystine via intramolecular [3 + 2] cycloaddition with a d.s. value of 80%. Danishefsky et al.217) synthesized pretyrosine, the biosynthetic precursor of (S)-tyrosine, by a [4 + 2]-cycloaddition applying an (S)-glutamic acid derivative as chiral auxiliary. Phenylglycine was used as the source of the chiral information in an asymmetric variation of a 1,3-dipolar cycloaddition, as reported by Grigg and Kemp et al. 218>. 

Pharmaceutical formulations consisting of poly-a-L-glutamic acid derivatives were prepared by Bonnet-Gonnet (3) and used in the prolonged release of D,L-a-tocopherol. 

Poly-a-L-glutamic acid derivatives prepared by Piccariello et al. (4) were functionalized with iV-octanoyl-L-triiododiyronine and used in the treatment of thyroid disorders. 

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

In this section we provide experimental procedures for the synthesis of various 2-nitrophenyl-containing amino acid derivatives glutamic acid derivative 109 230 (Scheme 28), glycine derivative 112 230 and aspartic acid derivative 114 230 (Scheme 29), Fmoc-protected tyrosine derivative 119 234 (Scheme 30), and glycine derivatives 120 235 and 122 232 (Scheme 31). 

Synthesis of Crown Ether Lysine and Glutamic Acid Derivatives... 

KOSiMe3 by a Beckmann-type rearrangement [39], and from glutamic acid derivatives by intramolecular acylation [40]. 

In an intramolecular variation [57], the acid-promoted alcoholysis of the (3-lactam ring in 10, Scheme 3, produced 2,3-aziridino-y-lactones 11, which are intermediates of glutamic acid derivatives with potential activity as excitatory neurotransmitter of the central nervous system. 

Michael addition of glycinate Schiff base 28 to a,/ -unsaturated carbonyl substrates with high enantioselectivity (Scheme 4.19) [53, 54]. With methyl acrylate as an acceptor, a-tert-butyl y-methyl ester of (S)-glutamic acid can be formed this functionalized glutamic acid derivative is very useful for synthetic applications because the two carboxyl groups are differentiated. Moreover, naturally occurring (S)-ornithine has been synthesized as its dihydrochloride in a concise manner by using acrylonitrile as an acceptor, as also included in Scheme 4.19... 

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