Methylamino acid

Fig. 8. Stmcture of (a) valinomycin and (J3) and enniatins and beauvericin. Hov = a-hydroxy-isovaleric acid and Lac = lactic acid. The /V-methylamino acid for enniatin A is isoleucine enniatin B, valine enniatin C, leucine and beauvericin, phenylalanine.

Transformation of the amino nitriles to the corresponding amino acids, with removal of the dioxane ring, is carried out in two steps. Treatment with concentrated hydrochloric acid results in the hydrolysis of both the nitrile and the acetal group, and in cyclization to the corresponding 3-substituted 5-hydroxyniethyl-3-methyl-2-oxo-6-phenylmorpholinc hydrochlorides. Oxidative cleavage with 2 N sodium hydroxide solution, air and Raney nickel at 120 CC (ca. 30 h) delivers the hydrochlorides of the free a-methylamino acids in high yield. 

This reaction has been used to prepare a-A-methylamino acids using (CH3)2BBr.191... 

The question was whether impurities were present in the samples analysed (Bada et al., 1983). In a more recent publication, Cronin and Pizzarello (1997) reported amino acid analyses using Murchison material in which an excess of L-enantiomers was present. Contamination with terrestrial biological material can be ruled out, as the amino acids in question are not proteinogenic a-methylamino acids, which occur either extremely seldom or not at all in terrestrial life forms, were detected. GLPC/mass spectrometry (MS) analysis gave the following enantiomeric excess (ee) values ... 

FIGURE 2.21 Experimental evidence indicates that products from BOP-mediated reactions do not originate from the benzotriazolyl ester. The use of BOP allows successful coupling of A-alkoxycarbonyl-A-methylamino acids, whereas the benzotriazolyl esters of these acids undergo aminolysis only with great difficulty. The higher ratio of products obtained from the BOP-mediated reaction in the competing reactions described implies a compound other than the benzotriazolyl ester as the precursor of the peptides. 

JR McDermott, NL Benoiton. JV-Methylamino acids in peptide synthesis. III. Racemization during deprotection by saponification and acidolysis. Can J Chem 51, 2555,... 

Treatment of compounds, especially esters (see Sections 3.11 and 4.20), /V-substituted cysteine esters (see Section 8.1), and fully substituted /V-methylamino-acid residues (see Section 8.14), by alkali. 

FIGURE 6.24 The cis and trans forms of the amide bond of a dipeptide ester and cyclization of the compound to the piperazine-2,5-dione. The tendency to cyclize is greater when the carboxy-terminal residue is proline or an IV-methylamino acid. In these cases the predominating form is cis, which places the amino and ester groups closer together. 

MONOMETHYLATIONOFAMINO GROUPS AND THE SYNTHESIS OF N-ALKOXYCARBONYL-N-METHYLAMINO ACIDS... 

FIGURE 8.16 Preparation of Cbz/Boc-/V-methylamino acids by methylation of Cbz/Boc-amino acids. [Benoiton et al., 1972]. Sodium hydride is added to substrate and methyl iodide in tetrahydrofuran, producing the sodium salt of the /V-methylated derivative. 

FIGURE 8.17 Preparation of Fmoc-A-methylamino acids by methylation of Fmoc-amino acids.90 Acid-catalyzed reaction of substrate with formaldehyde at elevated temperature with removal of water by azeotropic distillation produces the oxazolidinone, which is then opened and reduced to the A-methylated derivative. 

RK Olsen. A convenient synthesis of protected V-methylamino acid derivatives, (silver oxide and methyl iodide) J Org Chem 35, 1912, 1970. 

JR Coggins, NL Benoiton. Synthesis of V-methylamino acid derivatives from amino acid derivatives using sodium hydride/methyl iodide, (in dimethylformamide) Can J Chem 49, 1968, 1971. 

ST Cheung, NL Benoiton. V-Methylamino acids in peptide synthesis. V. The synthesis of V-terf-buiy I oxycarbonyl, V-methylamino acids by V-methylation. Can J Chem 55, 906, 1977. 

K Kaljuste, A Unden. New method for the synthesis of V-methylamino acids containing peptides by reductive methylation of amino groups on the solid phase. Int J Pept Prot Res 42, 118, 1993. 

THE DISTINCT CHIRAL SENSITIVITY OF N-METHYLAMINO ACID RESIDUES AND SENSITIVITY TO ACID OF ADJACENT PEPTIDE BONDS... 

FIGURE 8.20 Peptides activated at an IV-methylamino-acid residue are postulated to epimer-ize because of the formation of the oxazolonium ion. Evidence for the latter resides in spectroscopic studies,96 and the isolation of a substituted pyrrole that was formed when methyl propiolate was added to a solution of Z-Ala-MeLeu-OH in tetrahydrofuran 10 minutes after dicyclohexylcarbodiimide had been added.95 The acetylenic compound effected a 1,3-dipolar cycloaddition reaction (B), with release of carbon dioxide, with the zwitter-ion that was generated (A) by loss of a proton by the oxazolonium ion. 

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