Enamino-acids

Pyrrole synthesis from 1,3-dicarbonyl compounds (or enamino Ketones) and a-amino acids via cyclization of enamino acid intermediates. 

Preparation of /f-Enamino Acid Derivatives. The reaction of ketimines (7) with ALlV -carbonyldiimidazole (GDI) (1) in the presence of Bp3-OEt2 as catalyst affords -enamino carbonyUm-idazole derivatives (8) in good to excellent yields (eq 15). ... 

The reaction of P-keto acid derivatives and ammonia or amines relies on initial reaction with an aldehyde or ketone moiety. The carbonyl must be P- to the carboxyl group, however, in order to obtain the enamino acid or enamino-ester derivative (an enamine is a "vinyl amine," first used synthetically by Stork, and they are well known). These enamino derivatives are actually 3-aminopropenoic... 

ScHOLLKOPF et al (360) reacted a-metallated isocyanoacetic ester with aldehydes and ketones in aprotic solvents to form formyl-enamino acid esters (24) via intermediate oxazoline carboxylic acid esters. 

Dehydrodipeptides (35) have also been prepared from free enamino acid esters and cyclized after hydrazinolysis of the protective group (366, 368) giving (37). Condensation with carbonyl compounds makes possible the synthesis of unsymmetrical tetradehydropiperazinediones (36). 

The simplest and most satisfactory method of preparing arylidene-enamino acid esters is the P-elimination from 2-aryl-4-thiazolidinecarbo-xylic acid esters (40) on treatment with silver carbonate 287A). Arylidene-enamino acid N-hydroxysuccinimide esters were prepared and combined with amino acid esters to yield Schiff bases of dehydro-dipeptides. This elimination reaction of thiazolidine carboxylic acid esters has been applied to prepare the extremely unstable benzyUdene dehydroalanine ester, although it was impossible to isolate it. Nevertheless its existence could be proved without a doubt when the reaction was carried out at 0° in trideuterioacetonitrile solution and was followed by NMR spectrometry. Within one half hour at room temperature the unstable substance started to decompose. 

Breitholle and Stammer (68, 69) attempted to prepare free enamino acid anilides from the corresponding trifluoroacetyl compounds, which are readily obtainable via oxazolinones. Only in the case of the dehydro-... 

Only a few esters of dehydroamino acids are stable and these only as hydrochlorides, so that all the reactions at the amino group studied to date are electrophilic. As the enamino group is less nucleophilic than an amino group, enamino acid esters can only be acylated by the most reactive acid derivatives, such as acid chlorides (368, 373) and mixed anhydrides (69, 257, 313). Attempted peptide formation from acylamino acids and enamino acid esters by the DCCD or DCCD/hydroxysuccini-mide methods is unsuccessful. The formation of Schiff bases at the enamino group proceeds rather slowly, but can be achieved in the case of the stable dehydrovaline methyl ester by direct condensation with aromatic aldehydes (287, 352). 

For the construction of peptides with an N-methyldehydroamino acid unit, use can be made of the observation by Rich (328) that selective N-methylation of N-acyl enamino acid units can be carried out with methyl iodide/potassium carbonate in dimethylformamide. 

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