Amino acids thioamides

Various more or less efficient methods have been reported for the synthesis of 2-(l-ami-noalkyl)thiazole-4-carboxylic acids and their suitably protected derivatives. 237,539,541,558-568 Optimal conditions must be selected in these syntheses to prevent racemization at the chiral aminoalkyl moiety, e.g. when applying a modified Hantzsch synthesis 559 racemization has been observed to occur at the level of the starting Na-protected amino acid thioamide as well as in the base-mediated dehydration step of the intermediate hydroxydihydrothiazoles. 558 The 2-(aminoalkyl)thiazole-4-carboxylic acids are incorporated into the linear precursors by standard procedures of peptide synthesis, 237,514,529,539,552,555,558,564,569 and cyclization is pref-... 

N-Protected amino acid amides 14 react with tetraphosphorus decasulfide (P4S10) in the presence of NaF in DME at room temperature to give amino acid thioamides 15 that are... 

Thionation of Cbz-protected a-amino acid dimethylamides of type 6 proceeds smoothly under the standard conditions to give selectively Cbz-protected o -amino acid thioamides 7 (eq 3), i.e., thionation of carboxamides is preferred to that of carbamates. 

C-Terminal activation of peptides containing a terminal thioamide group results in thiazo-lone formation this leads to epimerization at the marked chiral centers (see Scheme 35) the thiazolone is only a weak acylating agent 500 The coupling yield may still be satisfactory, if achiral C-terminal amino acids are employed 488,503 ... 

An attractive method of preparation of the dithioesters of N-protected amino acids was described by Thorsen et a I.194 The methyl dithioesters were used in an activated form of amino acids for the synthesis of thioamide-modified peptides (see Section 10.9.1). 

The resulting triazoles can be N-alkylated by treatment with alkyl halides (0.25 mol/L, 30 equiv., DMF, NaOH), but mixtures of the 1-alkylated and 2-alkylated triazoles are obtained [255]. 1,2,4-Triazoles have also been prepared from N-amino-amidines (amidohydrazones Entry 4, Table 15.20), which were prepared from resin-bound thioamides by S-alkylation with methyl triflate followed by treatment with hydrazine [256]. 1,2,4-Tri azoles undergo Michael addition to polystyrene-bound a-acetamido acrylates to yield triazole-derived a-amino acids (Entry 7, Table 15.20). Benzotriazoles have been N-arylated on insoluble supports by treatment with aryl-boronic acids in the presence of catalytic amounts of copper salts (Entry 8, Table... 

The most common method for synthesizing peptide dithioesters is based on the Pinner reaction. N-Protected peptide nitriles react with thiols in the presence of HQ to give imi-dothioic acid ester hydrochlorides that are treated with H2S (Section 15.1.11.1). 1 61 A modification of this procedure is made by dissolving the nitriles in liquid HF and reacting with thiols to form imidothioic acid ester hydrofluorides, followed by thiolysis with H2S (Section 15.1.11.1.1). 7 The second approach is to synthesize the thiopiperidide derivative using Lawesson s reagent, followed by S-methylation with iodomethane and thiolysis with H2S (Section 15.1.11.2). 4 A modification of the Lawesson s procedure via a thioamide is also used to prepare amino acid dithioesters (Section 15.1.11.2.1). 8 ... 

Reaction of Amino Acids with Ammonia via Thioamides... 

Amino acid dithioesters have been used as building blocks for the synthesis of en-dothiopeptides, the dithioesters will condense with a-amino groups of N-unprotected amino acids to form thioamides. Preparation of optically active amino acid dithioesters and subsequent formation of thioamide bonds without racemization are two problems that need to be addressed when using this approach to prepare endothiopeptides. The Pinner reaction (Section 15.1.11.1) 1 and Lawesson s procedure (Section 15.1.11.2)M have been successfully used to prepare optically active amino acid dithioesters a modification of Lawesson s procedure via thioamides is also successful.[81... 

Scheme 4 N-Protected Amino Acid Dithioesters via Thioamides 81...

An improved procedure for condensation of dithioesters with a-amino groups of amino acids has been used to prepare several peptide thioamidesJ8 The N-protected amino acid dithioesters condense with alkali salts of a-amino acids, catalyzed by alkali fluoride in EtOH, to give the endothiopeptides within 60 minutes. Under these conditions, the thioamides are obtained without racemization. 

A class of simple, modular, and highly efficient a-amino acid amides ligands for Ru-and Rh-catalysed asymmetric transfer hydrogenation of aromatic ketones in propan-2-ol has been developed. A remarkable feature with these ligands is the switch of product enantioselectivity observed when the amide functionality is replaced by the corresponding thioamide. The results obtained have significant mechanistic implications... 

Analytical Properties Microcrystalline triacetylcellulose swells in organic solvents separation of racemic thioamides, sulfoxides, organophosphorus compounds, drugs, and amino acids derivatives separations of these racemates were achieved at pressures at or above 4.9 MPa Reference 10... 

Cyanoenamines 160 (R = CN, COOMe, COOCMe3, Br, N02, PhS02, 2-pyridyl) were prepared in 15-90% yields by the condensation of RCH2CN with thiolactam 159 in the presence of Ag2C03. Amino acid enamine derivatives 162 (R = CN, COOEt) were prepared similarly from thioamide 16168 5. 

In another attractive approach for synthesizing 3,4,5-trisubstituted 1,2,4-triazoles, the molecules are built up from a-amino adds anchored through their amino function to an activated carbonate resin [94]. These urethane-Hnked a-amino acids are coupled with amines. After conversion to thioamides, the trisub-stituted triazoles are obtained by treatment with hydrazines in the presence of Hg(OAc)2. 

Thiazol-a-amino acids (441) can be prepared by the Hantzsch thiazole synthesis of the thioamide... 

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