N-Methyl-L-valine

Amino-4,6-dimethyl-3-oxo-3//-phenoxazine-l,9-dicarboxylic acid also named actinocin is the chromophor of the red antineoplastic chromopeptide actinomycin D (formula A). Two cyclopenta-peptide lactone rings (amino acids L-threonine, D-valine, L-proline, sarcosine, and N-methyl-L-valine) are attached to the carboxy carbons of actinocin by two amide bonds involving the amino groups of threonine. 

Abbreviations AcAib, acetyl aminoisobutyric acid pheol, phenyl-alaninol Lac, L-lactic acid D-HIV, D- a - hydroxyisovaleric acid L-MeVal, N-methyl-L-valine Me, methyl. 

Figure I Structure of actinomvein D Sar and Meval are N-methylgtycine and N methyl-L-valine. respectively.

A soln. of L-valine in 2 N NaOH vigorously stirred, treated with benzaldehyde, after 15-20 min. NaBH4 added below 15°, stirring continued 0.5 hr., the treatment with benzaldehyde and NaBH4 repeated, finally stirred 2 hrs. N-benzyl-L-valine (Y 86%) heated 1.5 hrs. on a steam bath with formic acid and 38-40%-formaldehyde soln. N-benzyl-N-methyl-L-valine (Y 92%) dissolved in 90%-acetic acid, and hydrogenated with 5%-Pd-on-carbon N-methyl-L-valine (Y ... 

CH3NH + CICOOGH2G6H5 CH3NGOOCH2GeH5 Carbobenzoxy chloride and 0.9 N LiOH added dropwise and simultaneously below 10° to a soln. of N-methyl-L-valine and LiOH in tetrahydrofuran-water so that the soln. remains phenolphthalein-alkaline, stirring continued 4 hrs. at 10°, and allowed to stand 16 hrs. at 2-4° carbobenzoxy-N-methylvaline. Y 74-89%. P. A.Plattner et al., Helv. 4-6, 927 (1963). 

Fig. 1. Actinomycin IV(d). The chromophore, actinocin (2-amino-4,6-dimethyl-3-phenoxazinone-i,9-dicarboxylic acid), is identical in all of the actinomycins examined. The sequence of amino acids is L-threonine, D-valine (n-val), L-proline (L-pro), sarcosine (sar), N-methyl-L-valine...

Soon after, Brockmann and Grubhofer (1949) isolated from a culture of 5. chrysomallus another actinomycin which they designated as C. It appeared to be different from actinomycin A or B on the basis of crystal form, melting point, solubihty, infrared spectrum, analytical composition and the nature of the amino acids present (Brockmann and Grubhofer, 1950,1951). Hydrolysates of actinomycin C contained the six amino acids D-valine, sarcosine, L-threonine, L-proline, N-methyl-L-valine and D-alloisoleucine. 

Biogenesis of the amino acids, D-valine and D-alloisoleucine, 4-oxo-L-proline and hydroxy-L-proline, sarcosine, N-methyl-L-valine, and N-methylalanine. 

MHAA-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine are all converted to compounds having spectral charac teristi cs of phenoxazinones. The relative ratesof reaction and spectral maxima of the phenoxazinones formed from 3-HAA, 4-MHAA, the 4-MHAA peptides and related substances are shown in Table 7. The rate of the reaction is only 10 to 20% faster when the 4MHAA peptides are used rather than 3-HAA as substrate. The Km for the substrates tested was calculated to be approximately 1 to 2 X 10 M. 

MHAA-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine 122 448... 

Muratake, H. and Natsume, M. (1991a) Synthesis of teleocidins A, B and their congeners. Part 1. An efficient synthesis method of N-(7-alkyl-4-indolyl)-N-methyl-L-valine esters, essential intermediates for teleocidin synthesis. Tetrahedron, 47, 8535-8544. 

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