Glutamic acid 1,5-anhydrides derivatives

A series of new amino acid derivatives having pendant nucleic acid bases was prepared by the reaction of L-lysine and L-glutamic acid with the nucleic acid bases. These amino acids were further polymerized by using the N-carboxyamino acid anhydride ( NCA ) method. Alternatively, the nucleic acid base substituted poly-L-lysines were also prepared by using polymer reactions which include the reaction of carboxyethyl derivatives of the bases onto poly-L-lysine. Physico-chemical properties of the polymers obtained were given. 

D-Glutamic acid-g-(t-butyl)ester N-carboxy anhydride was previously polymerized by Fujimoto et al. (1) in a l,2-dichloroethane/l,4-dioxane mixture using sodium 4-methyl-2-pyrrolidone as initiator. Additional derivatives were... 

Correspondingly, the use of other anhydrides of aliphatic acids provides the appropriate 2-acyl derivatives. Cyclization of glutamic acid dipeptides... 

In a variant of the above approach, Temple et al. [37c] converted (III. 129) successively to the dichloride (III.134) (72%) and the 2-amino-4(377)-oxo derivative (III.135) (75%). Treatment of (III.135) with acetic anhydride and sulphuric acid followed directly by bromination at 95 °C in acetic acid in the presence of sodium acetate, condensation with 7V-(4-aminobenzoyl)-L-glutamic acid, and alkaline hydrolysis afforded a low yield of (III. 124), whose UV spectral properties (pH 1) 250 nm (e 15,100), 298 (19,400) ... 

A derivative of pyrrolidino[2,l-c]-l,4-benzodiazcpinc 266 was synthesized by the reaction of 7-fluoro-l-methylisatoic anhydride with /.-glutamic acid in the presence of triethylamine [177],... 

Rupintrivir (72, Scheme 2.11) is a peptidomimetic protease inhibitor developed by Agouron Pharmaceuticals (San Diego, CA) for the treatment of human rhinovirus (HRV). A key component of the rupintrivir pharmacophore is the a,(3-unsaturated ester moiety, which acts as a Michael acceptor, forming a covalent bond with cysteine residues in the active site of HRV 3C protease. Synthesis of the 7-amino a,(3-unsaturated ester portion of rupintrivir involved coupling L-glutamic acid derivative 66 with 4-benzyloxazolidinone 67 via a mixed anhydride. Formation of the corresponding sodium enolate, followed by alkylation with allyl iodide 69, gave the a-allyl amide 70. 

A -Protected amino acids and peptides are rapidly converted to the corresponding amino alcohols in high yields with complete retention of optical purity via reduction of the mixed anhydride by cold Sodium Borohydride in THE with dropwise addition of methanol (eq 16). The disulfide bridges of cystine, the methyl and benzyl esters of w-carboxyl-protected glutamic and aspartic acids of peptides, and Ai-Cbz and IV-Boc protection are compatible with the methodology. The anhydrides derived from ethyl chloroformate are superior to isobutyl and benzyl carbonates both in terms of yield and retention of optical purity. 

The catalysis of hydrolysis of carboxylic acid derivatives by weak bases has not been carefully studied until relatively recently. Koshland reported in 1952 the catalysis of acetyl phosphate hydrolysis by pyridine Bafna and Gold (1953) reported the pyridine-catalyzed hydrolysis of acetic anhydride. A short time later the catalysis of aromatic ester hydrolysis by imidazole was demonstrated (Bender and Turnquest, 1957 a, b Bruice and Schmir, 1957). Since that time a large amount of work has been devoted to the understanding of catalyzed ester reactions. Much of the work in this area has been carried out with the purpose of inquiry into the mode of action of hydrolytic enzymes. These enzymes contain on their backbone weak potential catalytic bases or acids, such as imidazole in the form of histidine, carboxylate in the form of aspartate and glutamate, etc. As a result of the enormous effort put into the study of nucleophilic displacements at the carbonyl carbon, a fair understanding of these reactions has resulted. An excellent review is available for work up to 1960 (Bender, 1960). In addition, this subject has been... 

For the preparation of the 2-amino-4(3i7)-oxo analogues of this series, the 2,4-diamino-9,10-dehydro derivative (IV.175) was converted to (IV.187) (88%, yield) by heating in 1 M NaOH under reflux for 3 h [140a]. Treatment of (IV.187) with acetic anhydride containing a catalytic amount of 4- NJ -dimethylamino)pyridine afforded the 2-acetamido-4-oxo mixed anhydride (IV. 188) (84%), which on careful alkaline hydrolysis was converted to the protected acid (IV. 189) (77%,). Coupling to diethyl L-glutamate in V-methyl-pyrrolidin-2-one in the presence of phenyl iV-phenylphosphoramidochloridate... 

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