Amino acids reaction with anhydrides

The most suitable synthetic method for these products is the heterocyc-lization reaction of N-thioacyl derivatives of amino acids (202) with phosphorus tribromide (378, 442-450, 559, 560) or anhydrous trifluoroacetic acid (448, 449, 451, 452) (Scheme 103). Treatment of N-thioacyl amino acids with acetic anhydride leads directly to the thiazolylacetate without isolation of an intermediate thiazolinone (365. 452). 2-Alkoxy-derivatives of A-2-thiazoline-5-one, however, can be obtained without acetylation by this method (453, 454). 

Reaction of the thia-amino acid 392 with trifluoroacetic anhydride gave the 2,2,2-trifluoro-l-[7-(trifluoromethyl)-l//-pyrrolo[l,2-c]-[l,3]thiazol-6-yl] ethanone pyrrole 395. The formation of the pyrrole can be rationalized by a sequence involving trifluoroacetylation of the enamine 392 affording dione 393 followed by loss of water and carbon dioxide to give the aromatic product 395. These decarboxylations afford fluorinated derivatives of heterocyclic skeletons known to exhibit interesting biological activity (Scheme 58) <2000T7267>. 

Despite the uncertainties regarding regiochemistry, the reaction of propiolates with miinchnones has found use in synthesis. Kane and co-workers (84) synthesized the calcium channel activator FPL 64176 (161) using a mtinchnone cycloaddition protocol. Thus, reaction of amino acid 158 with acetic anhydride in the presence of acetylenic dipolarophUe 159 gave pyrrole 160 in 49% yield. Base-induced elimination of the 4-nitrophenethyl protecting group afforded FPL 64176 (161) in 85% yield. 

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-... 

Huisgen and coworkers have also described the cycloaddition behavior of the munchnones , unstable mesoionic A2-oxazolium 5-oxides with azomethine ylide character.166 Their reactions closely parallel those of the related sydnones. These mesoionic dipoles are readily prepared by cyclodehydration of N-acyl amino acids (216) with reagents such as acetic anhydride. The reaction of munchnones with alkynic dipolarophiles constitutes a pyrrole synthesis of broad scope.158-160 1,3-Dipolar cycloaddition of alkynes to the A2-oxazolium 5-oxide (217), followed by cycloreversion of carbon dioxide from the initially formed adduct (218), gives pyrrole derivative (219 Scheme 51) in good yield. Cycloaddition studies of munchnones with other dipolarophiles have resulted in practical, unique syntheses of numerous functionalized monocyclic and ring-annulated heterocycles.167-169... 

Wilchek, M., Ariely, S., and Patchornik, A., The reaction of asparagine, glutamine, and derivatives with phosgene, J. Org. Chem. 33, 1258-1259, 1968 Hamilton, R.D. and Lyman, D.J., Preparation of A-carboxy-a-amino acid anhydrides by the reaction of copper(II)-amino acid complexes with phosgene, J. Org. Chem. 34, 243-244,1969 Pohl, L.R., Bhooshan, B.,... 

The polymerization of a-amino acid N-carboxy anhydride (NCA) is a well-known reaction for the preparation of poly(a-amino acid) with high molecular weight, which has played an important role as a model of protein (S2). 

Bodanszky and Birkhimer found that in certain cases an N-protected amino acid reacts with p-nitrophenol in the presence of 2 equivalents of ethoxyacetylene at 50° for 1 hr. and at room temperature for 24 hrs. to give the p-nitrophenyl ester. However, the reaction often stops at the ethoxyvinyl ester stage or at the anhydride stage. 

The most useful procedure utilises a 1,4-keto-ester giving a dihydro-pyridazinone, which can be easily dehydrogenated to the fully aromatic heterocycle, often by C-bromination then dehydrobromination alternatively, simple air oxidation can often suffice. 6-Aryl-pyridazin-3-ones have been produced by this route in a number of ways using an a-amino nitrile as a masked ketone in the four-carbon component, or by reaction of an acetophenone with glyoxylic acid and then hydrazine. Friedel-Crafts acylation using succinic anhydride is an alternative route to 1,4-keto-acids, reaction with hydrazine giving 6-aryl-pyridazinones. Alkylation of an enamine with a phenacyl bromide prodnces 1-aryl-l,4-diketones, allowing synthesis of 3-aryl-pyridazines. ... 

Kawase described a direct and general synthesis of 2,4-disubstituted 5-(trifluoromethyl)oxazoles 500 from reaction of an A -acyl-A-benzyl amino acid 499 with trifluoroacetic anhydride in pyridine (Scheme 1.136). In general, the best... 

The preparation of 4-(3-pyridylmethyl)oxazolidine-2,5-dione 1194, the NCA of j8-pyridylalanine, is made difficult by the presence of a pyridyl group in the amino acid. The pyridyl group complicated attempts to phosgenate the amino acid, since hydrogen chloride generated in the phosgenation reaction formed insoluble salts with the amino acid and with any anhydride that may have formed [877]. 

N-Carboxy anhydrides 1201 of several a-amino acids, including jS-chloro-L-alanine, can be formed by reaction of an N-tert-butoxycarbonyl (Boc) amino acid (1199) with tert-butyldimethylsilyl chloride and subsequent treatment of the resulting silyl ester 1200 with oxalyl chloride in the presence of dimethylformamide [821],... 

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