Carboxylic acid amide peptides

A. T. Hagler, A. Lapicirella, Spatial Electron Distribution and Population Analysis of Amides, Carboxylic Acid, and Peptides, and Their Relation to Empirical Potential Functions , Biopolymers 1976, 1167-1200 A. T. Hagler, L. Leiserowitz, M. Tuval, Experimental and Theoretical Studies of the Barrier to Rotation about the N-C° and Ca-C Bonds ([Pg.369]

There has been a study of the mechanism of the activation of carboxylic acids to peptide formation by chloro-s -triazines in combination with tertiary amines. The first step, exemplified in Scheme 2 by the reaction of 2-chloro-4,6-disubstituted-l,3,5-triazines (18) with A -methylmorpholine, is formation of a quaternary triazinylammonium salt (20). Here there is NMR evidence for the formation at —50°C of the intermediate (19), showing that the substitution involves the two-step SnAt mechanism rather than a synchronous pathway. The subsequent reaction of (20) with a carboxylic acid yields the 2-acyloxy derivative (21), which carries an excellent leaving group for the amide-forming step. ... 

Carboxylic acids and primary amines react to form carboxylic acid amides (R-NH-CO-R ). The amino acid constituents of peptides and proteins are linked by carboxylic acid amide bonds, which are therefore also known as peptide bonds (see p. 66). 

The Influence of Fluoro Substituents On the Reactivity of Carboxylic Acids, Amides, and Peptides in Enzyme-Catalyzed Reactions ... 

During solid phase synthesis peptides are bound to the solid support by means of the C-terminal carboxyl group. The properties of the anchor group positioned between the growing oligomer and the solid support are crucial for the success of a solid phase synthesis. Usually, specialised linkers are used which provide either peptide carboxylic acids or peptide carboxylic amides upon cleavage [4]. A cleavage mechanism that proceeds by a nucleophilic attack... 

Classical reactions involving nucleophiles such as saponification ("OH as the nucleophile), aminolysis (with amines also ammonia in ammonolysis reactions), transesterification (alkoxides, "OR) and others (hydrazinolysis, hydroxamic acid synthesis, etc.) have been adapted to solid phane and used to obtain, for instance, carboxylic acids, amides and esters. Internal or intramolecular nucleophilic attack has been employed to obtain cyclic products such as lactones, lactams (including cyclic peptides) and a great variety of heterocycles (hydantoins, diketopiperazines, benzodiazepinones, etc.). 

In 1957, Schlogl reported the synthesis and characterization of several ferrocene amino acids, including ferrocenylala-nine (Fer, 14 Scheme 18). Other organometallic amino acids include alanine, phenylalanine (Phe), glycine derivatives, as well as further ferrocene-based amino acids, which are discussed below. The Schlogl paper also describes the reaction of ferrocene carboxylic acid and ferrocene carbaldehyde with amino acids. The chemistry was later picked up in numerous publications, and ferrocene carboxylic acid amides or ferrocene imines with basically all amino acids and many dipeptides were reported. Such conju tes may serve as ligands for other transition metal ions. " Kraatz has prepared ferrocene carboxylic acid conju tes with short peptides that serve as enzyme inhibitors. ... 

Triphenyl phosphine, mercuric chloride, disulfide Subst. carboxylic acid amides from carboxylic acids Redoxidative peptide synthesis... 

Peptides (s. a. Carboxylic acid amides, subst., Peptoids)... 

Diphenyl phosphoryl azide in dimethylformamide followed by triethylamine added at or below 0° to a soln. of N-carbobenzoxy-L-leucyl-L-leucine and L-valyl-L-phenylalanine methyl ester hydrochloride in the same solvent, stirred several hrs. at the above temp, and overnight at room temp. -> product. Y 87%. - Practically no racemization occurred. F. e., also direct prepn. of urethans from carboxylic acids (cf. Synth. Meth. 17, 393) by a simplified Curtius degradation, s. T. Shioiri, K. Ninomiya, and S. Yamada, Am. Soc. 94, 6203 (1972) Tetrah. Let. 1973, 2343 synthesis of N-subst. carboxylic acid amides and peptides with diethyl phosphoryl cyanide s. Tetrah. Let. 1973, 1595 coupling reagents in peptide synthesis, review, s. Y. S. Klausner and M. Bodansky, Synthesis 1972, 453 review of peptide synthesis s. J. Meienhofer, Chem. Technol. 3, 242 (1973). 

Peptide synthesis—N-Decarbobenzoxylation s. 13, 387 Subst. carboxylic acid amides from iminoesters G(OR)( NR ) GONRR ... 

Hagler, A.T.,and Lapiccirella, A., 1976, Special electron distribution and population analysis of amides, carboxylic acids and peptides, and their relation to empirical potential functions, Biopolymers, 15 1167. 

In synthetic target molecules esters, lactones, amides, and lactams are the most common carboxylic acid derivatives. In order to synthesize them from carboxylic acids one has generally to produce an activated acid derivative, and an enormous variety of activating reagents is known, mostly developed for peptide syntheses (M. Bodanszky, 1976). In actual syntheses of complex esters and amides, however, only a small selection of these remedies is used, and we shall mention only generally applicable methods. The classic means of activating carboxyl groups arc the acyl azide method of Curtius and the acyl chloride method of Emil Fischer. 

Ammo acids are carboxylic acids that contain an amine function An amide bond between the carboxylic acid function of one ammo acid and the ammo nitrogen of another is called a peptide bond... 

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