Carboxylic acid anhydrides with amino acids

For the production of glycinamide ribonucleotide, an acyl phosphate (anhydride) intermediate is formed by reaction of ATP -with a carboxylic acid of an amino acid (glycine), whereas in the production of guanylate (GMP) a phosphoryl ester intermediate is formed by reaction of ATP with an enol alcohol on the purine ring of the nucleotide. 

The reaction of pyromellitic dianhydride or benzophenone-3,3, 4,4 -tetra-carboxylic anhydride with amino acids or lactams followed by condensation of the resulting diacids with diacetates of hydoquinone, 2,6-dihydroxynaph-thalene or 4,4 -dihydroxybiphenyl produced layer polymers (42). With the exception of the polymer with y=ll, all the polymers based on Ar = 4,4 -biphenylyl exhibit a smectic mesophase. The polymer with y = 10 and Ar = 1,4-phenylene exhibits a smectic mesophase. Polymers based on Ar = 1,4-phenylene or 2,6-naphthalene melt directly into an isotropic phase. 

This reaction occurs in two steps in the enzyme s active site. In step (Fig. 27-14) an enzyme-bound intermediate, aminoacyl adenylate (aminoacyl-AMP), forms when the carboxyl group of the amino acid reacts with the a-phosphoryl group of ATP to form an anhydride linkage, with displacement of pyrophosphate. In the sec-... 

Amino-2-imino-4-methylthiazoline hydrochloride (112) and aminium salts (114) react with carboxylic acid anhydrides to give thiazolo[3,2-6]-s-triazoles (113) (76JHC1225, 74JHC459). 

The starting materials for the preparation of 1,3-benzotellurazoles are aromatic tellurium compounds that contain an amino functionality in an orv/to-position to the tellurium atom. The reduction of 2-benzeneazophenyl tellurium trichloride with sodium borohydride in ethanol generates 2-aminobenzenetellurol. This compound is acylated with carboxylic acid anhydrides and the acylaminobenzenetellurol cyclized by treatment with concentrated... 

Moderate to good yields of 2-substituted 8,9-dimethylpurine-6-carbonitriles 7 are obtained by reaction of 5-amino-4-[cyano(imino)methyl]-l,2-dimethylimidazole with carboxylic acid anhydrides. 

Cyclodehydration of a-(thioaroylthio)- or a-(thiocarbamoylthio)carboxylic acids (96) with acetic anhydride in the presence of catalytic amounts of boron trifluoride etherate, or with a mixture of acetic anhydride and triethylamine (1 1), leads to the 2-aryl- or 2-amino-l,3-dithiolium-4-olates (97) listed in Table VIII.Chemical properties, dipole moments, NMR, IR, and UV spectra, and charge distribution calculations are consistent with a mesoionic structure. " ... 

Carbodiimides, in particular dicyclohexylcarbodiimide, have been applied in many syntheses where dehydration had to be performed under mild conditions. It is therefore no surprise that this reagent was also introduced for the synthesis of acid anhydrides from carboxylic acids." " In order to avoid N-acylation the reactions are carried out at low temperature. First 0-acylisoureas are formed, which then react further with free acid to the acid anhydride (equation 34). The reaction has been exploited in particular for the preparation of peptides." )V-alkoxycarbonyl-protected amino acids can be transformed in high yield to the corresponding anhydrides, which themselves are activated acid derivatives and may be converted to peptides. As in many other examples polymer-bound carbodiimides may prove superior sometimes, as the isolation of the products is facilitated. Easy preparation of acid anhydrides is possible in this way." ... 

Mixed anhydrides of carboxylic acids (RCO2H) and thiohydroxamic acid react with Sb(SPh)3 in the presence of O2 and water to give alcohols (ROH) via RSb(SPh)2 intermediates (Scheme 14.7) [28]. Both thioethers and sulfoxides bearing a hydrogen atoms are converted to a-fluorothioethers by treatment wifh (diefhylamino)sulfur trifluoride under Sb(.T, catalysis (Scheme 14.8) [29]. Treatment of 2-amino-6-halo nucleosides with tert-butyl nitrite in the presence of SbCls affords the 2-chloro-6-halopurine nucleosides (Scheme 14.9) [30]. 

The reagent promotes the coupling in high yields of acylamino acids with amino acid esters in benzene, ethanol, or THF at room temperature. No racemization was detected in the supersensitive Young test, and Bz-Leu-Gly-OEt, an 33.5°, was synthesized in 95% yield. Activation of the carboxyl group involves the transient formation of a mixed carbonic anhydride.3... 

An ester-like combination of the carboxyl group of an amino acid with a hydroxyl group for the same reasons is not possible, nor is the acid anhydride method of combination possible. A further reason... 

Thioesters.—Mixed anhydrides prepared from 2,4,6-trichlorobenzyl chloride and a carboxylic acid react with various thiols in the presence of 4-dimethyl-aminopyridine to give thioesters in 78—86% isolated yield.Somewhat less impressive yields were obtained in a few of the cases studied when l-fluoro-2,4,6-trinitrobenzene was used to couple the acid and the thiol.Treatment of 1-acylimidazoles with thiols in the presence of a catalytic amount of Mg(OEt)2 furnishes thioesters in good yields. Diphenyl-2-oxo-3-oxazolinylphosphonate brings about effective reaction between acids and thiols. Thiolacetates are efficiently prepared using the reaction of an alcohol with triphenylphosphine and di-isopropyl azodicarboxylate in the presence of thiolacetic acid/ A synthesis of some amino-acid derivatives containing the thioester functional group is achieved by the reaction of a vinyloxyborane with a Schiffs base (Scheme 56). ... 

A minimal NRPS module consists of an adenylation domain (A), condensation domain (C) and a peptidyl-carrier protein (PCP). In the first instance, the substrate-specific adenylation domain activates the carboxyl region of the amino acid with ATP, forming the mixed acyl-phosphoric acid anhydride with AMP, followed by loading onto the phosphopanthetheine moiety of the PCP. The condensation domain subsequently catalyses the nucleophific attack of the amino group of the previously activated amino acid, to the carbonyl of the tethered acyl group from the previous module [38, 39]. This results in the formation of a new peptide bond between the two units (Fig. 1.15). 

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