Valine methyl group

Strassman et al. (144), on the basis of the equal incorporation of lactate C-2 into valine C-2 and C-3, suggested that valine synthesis was initiated by the condensation of two pyruvate molecules, similar to the known condensation of pyruvate and acetaldehyde to yield acetolactic acid (162). The methyl group of pyruvate was indicated to be the precursor of the valine methyl groups. To explain this required a migration of the methyl group as in the pinacol rearrangement. 

The three staggered conformations are different for valine because the three groups attached to Cp are different. The first staggered conformation (b) is less crowded and energetically most favored because the two methyl groups bound to Cp are both close to the small H atom bound to Ca-... 

Although not of fatty acid origin another group of scarab beetles utilizes amino acid derivatives as pheromones [119]. The large black chafer, Holotrichia parallela, uses L-isoleucine methyl ester [ 120] and the cranberry white grub, Phyllophaga anxia, uses both L-isoleucine and i.-valine methyl esters [121]. More recently L-isoleucine methyl ester, N-formyl L-isoleucine methyl ester, and N-acetyl L-isoleucine methyl ester were identified in the scarab beetle Phyllophaga elenans [ 122]. These pheromone components are obviously derived from the amino acids isoleucine and valine. 

The maximum observed free energy difference between two enantiomeric host-guest complexes in which one 1,1 -dinaphthyl element is the only source of chirality in the crown ether is about 0.3 kcal mol-1. Improvement of the free energy difference can be achieved by introduction of two such elements. Unfortunately crown ethers with three 1,1 -dinaphthyl groups did not form complexes with primary ammonium salts (de Jong et al., 1975). The dilocular chiral crown ether [294] forms complexes of different stability with R- and 5-cr-phenylethylammonium hexafluorophosphate. The (J )-J J -[284] complex was the more stable by 0.3 kcal mol-1 at 0°C (EDC value 1.77) (Kyba et al., 1973b). Crown ether [284] also discriminates between the two enantiomers of phenylglycine methyl ester hexafluorophosphate and valine methyl ester... 

Additional experiments were performed to examine the role of the molecular size of the host enantioselectivity. Since the methyl groups in methylated jS-CD orient themselves toward the center of the cavity, it is expected that decreasing the extent of methyl derivatization in jS-CD from 21 (the permethylated jS-CD) to 14 methyl groups increases the effective size of the cavity." " As a matter of fact, the enantioselectivity of valine (kolkL = 0.32 with 21-methyl j8-CD) increases to W l = 0.18 with 14-methyl jS-CD. No significant effect of the cavity size is observed with the smaller alanine. 

Cyclosporin A contains II amino acids, joined in a cyclic strncture by peptide bonds. The structure is also stabilized by intramolecular hydrogen bonds. Only two of the amino acids, i.e. alanine and valine, are typical of proteins. The compound contains several A-methylated amino acid residues, together with the even less common L-a-aminobutyric acid and an Ai-methylated butenylmethylthreonine. There is one o-amino acid, i.e. o-alanine, and the assembly of the polypeptide chain is known to start from this residue. Many of the other natural cyclosporin structures differ only with respect to a single amino acid (the a-aminobutyric acid residue) or the number of amino acids that have the extra Ai-methyl group. 

The carbon skeletons of methionine, isoleucine, threonine, and valine are degraded by pathways that yield suc-cinyl-CoA (Fig. 18-27), an intermediate of the citric acid cycle. Methionine donates its methyl group to one of several possible acceptors through S-adenosytmethionine,... 

The third type of carbon-branched unit is 2-oxoisovalerate, from which valine is formed by transamination. The starting units are two molecules of pyruvate which combine in a thiamin diphosphate-dependent a condensation with decarboxylation. The resulting a-acetolactate contains a branched chain but is quite unsuitable for formation of an a amino acid. A rearrangement moves the methyl group to the (3 position (Fig. 24-17), and elimination of water from the diol forms the enol of the desired a-oxo acid (Fig. 17-19). The precursor of isoleucine is formed in an analogous way by condensation, with decarboxylation of one molecule of pyruvate with one of 2-oxobutyrate. 

Two molecules of pyruvate can react to give a common precursor to valine, leucine, and pantoic acid. An isomerization step involving shift of a methyl group from one carbon to another is involved. 

Figure 3 describes the preparation of A-co-undecenoyl-L-valine CSP bonded to silica gel. The carboxylic acid group of L-valine was protected by the reaction with isobutylene using the method of Roeske [47]. The formed tert-butyl ester of L-valine was precipitated from diethyl ether as the oxalate by the dropwise addition of a solution of 10% oxalic acid in absolute ethanol. The precipitate is dried and the oxalate group is removed by the reaction of sodium hydroxide. The tert-butyl ester of L-valine was treated with undecenoic acid in tetrahydrofuran (THF), which resulted in A-co-undecenoyl-L-valine methyl ester. In another step, lOmM of monochlorosilane was dissolved in 20 mL of dry pyridine and was allowed to react with /V -to - u ndccenoyl-L-valine methyl ester. 

The biosynthesis of the p-lactam antibiotic penicillin (Fig. 65), and also of cephalosporin, involves incorporation of L-valine and the question arises as to which of the two diastereotopic terminal methyl groups of the valine occupies which position in the penicillin. (In the case of cephalosporin, the question is as to which methyl group is incorporated into the six-membered ring and which becomes the methylene group of the carbinyl acetate.) The problem has been solved by two groups 65d,141) by synthesis of specifically 13C methyl labeled valine (cf. Fig. 42, and p. 35) which was then biosynthetically incorporated in the antibiotics. The position of the 13C in the resulting antibiotic molecules was determined by 13C NMR spectroscopy. 

The results are summarized in Fig. 65,36 The position of labeling of the cephalosporin follows directly from the position, in the 13C spectrum, of the peak enhanced by labeling when the precursor is stereospecifically methyl-13C labeled valine. The position of labeling of the penicillin, a or p, was deduced on the basis of an earlier assignment142) of the two signals due to the diastereotopic methyl groups in the spectrum of the un labeled material. 

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