V-Methylamino acids

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.

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 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. 

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. 

JR McDermott, NL Benoiton. V-Methylamino acids in peptide synthesis. II. A new synthesis of /V-benzyloxycarbonyl-V-methylamino acids. Can J Chem 51,1915,1973. 

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. 

Peptides with up to 166 amino acids (aglycon of erythropoietin [34]) have been prepared using the Fmoc strategy on cross-linked polystyrene. The preparation of peptides containing several /V-methylamino acids (e.g. cyclosporine [35,36]) has also been successfully performed using Fmoc protection. Flowever, such difficult peptides require careful planning of the synthesis and often the use of special coupling techniques. 

Planar cis and trans isomers (Figure 2.1(a)) are the most stable configurations, because the planar structure involves maximum orbital overlap. For the majority of peptides built up from a-amino acids, the amide bond adopts the trans geometry, a-Imino acids (notably proline but also /V-methylamino acids), as well as a-methyl-a-... 

FIGURE 8.19 Data showing the relative sensitivities to isomerization of /V-methylamino-and amino-acid residues under conditions of saponification, acidolysis by HBr (5.7 M = saturated) in anhydrous acetic acid and aminolysis of the mixed anhydrides by H-Gly-OBzl TosOH/EtgN.94 lie = isoleucine. 

Chemical Name V,V-dimethylcarbamoyloxyimino-2-(methylthio)acetamide ethanimidothioic acid, 2-(dimethylamino)-V-[[(methylamino)carbonyl]oxy]-2-oxo-methyl ester Uses insecticide/acaricide/nematicide CAS Registry No 23135-22-0 Molecular Formula C7H13N303S Molecular Weight 219.261 Melting Point (°C) ... 

General synthetic methods of preparation pf a-monoesters and a-mono-amides of MTX were also described by Piper et al. [240], The key intermediate in their scheme was 2,4-diamino-6-bromomethylpteridine, which could be condensed, for example, with a-methyl V-[4-(V-methylamino)ben-zoyl]-L-glutamate or A -[4-(V-methylamino)benzoyl]-L-glutamic acid a-amide... 

Diamino-6-hydroxymethylpteridine (VIII. 155) [302,303] was brominated with dibromotriphenylphosphorane essentially as described by Piper and Montgomery [247], but isolation and purification of 2,4-diamino-6-bromome-thylpteridine hydrobromide ((VIII.156) - HBr) was omitted in favour of condensing the bromide in situ with 4-(V-methylamino)benzoic acid to obtain... 

Lower homologues of (VIII.264) have likewise been prepared in the form of the L-ornithine analogue (VIII.268), the 2,4-diaminobutyric acid analogue (VIII.269), and the 2,3-diaminopropionic acid analogue (VIII.270). In one synthetic approach [368], 2,4-diamino-6-bromomethylpteridine was condensed with ethyl IV -Boc-A -[4-(V-methylamino)benzoyl]-L-2,4-diaminobut-... 

Example Miller and Rich investigated the conformational consequences of substitution s on an amino acid in cyclosporin A. an importan t iininunosnppressive dnig. One of th e ammo acids iii this cyclic iin decapeptide is (2.v, ir. 4r, 5f )-3-nydroxy-4-methyl-2-(methylamino)-6-octenoic acid (MeBmtli. It is essential for biological activitv. 

C17H21NO2 60725-36-2) see Nefopam a-[/V-(2-hydroxyethyl)methylamino]propiophenone (C 2H,7N02) see Phendimetrazine l-(2-hydroxyethyl)-4-(2-methylbenzyl)piperazine (C13H20N2O 40004-66-8) see Chlorbenzoxamine [2K-[2a(7f )3P(7t )]]-3-(l-hydroxyethyl)-Y-methyl-p,4-di-oxo-2-azetidinebutanoic acid (4-nitropheiiyl)methyl ester (C,7H2oN207 90822-23-4) see Meropenem... 

Methoxy-6,7,)V-trimethyl-3-methylamino-2-quinoxalinecarboxamide(16)gave 5-methoxy-6,7-dimethyl-3-methylamino-2-quinoxalinecarboxylic acid (17) (NaOH, H20, MeOH, reflux, 3 h 89%).742... 

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