D- and l- Leucine

A further method to induce chirality in the pyridoxamine-mediated transamination reactions was developed by Kuzuhara et al. [13]. They synthesized optically resolved pyridinophanes (21, 22) having a nonbranched ansa chain" between the 2 - and 5 -positions of pyridoxamine. With the five-carbon chain in 21 and 22, the two isomers do not interconvert readily. In the presence of zinc(n) in organic solvents such as methanol, tert-butanol, acetonitrile, and nitromethane, they observed stereoselective transamination between pyridinophanes and keto acids. The highest ee%s are 95 % for d-and L-leucine by reaction of the corresponding a-keto acid with (S)- and (R)- 22, respectively. On the basis of kinetic analysis of the transamination reactions, Kuzuhara et al. originally proposed a mechanism for the asymmetric induction through kinetically controlled stereoselective protonation to the carboanion attached to an octahedral Zn(n) chelate intermediate. However, they subsequently raised some questions about this proposal [14]. 

Figure 22.7 shows the plots of the observed isotropic chemical shifts (Sjso) of Gly, L-Ala, L-valine (u-Val), d and L-leucine (u-Leu), and L-aspartic acid (l-Asp) C=0 carbons against the N---0 hydrogen-bond length (Rn...q) (Table... 

L-Amino acids are the naturally occurring form both in proteins and as free amino acids, and the ability of different experimental animals to use different optical isomers of the amino acids has been studied. The chick is only able to use the L-form of threonine, isoleucine and valine but can use D- and L-leucine equally. It can use both D- and L-tryptophan, although the D-form is less effective (see Fisher, 1954). This probably relates to the presence of specific racemases that enable certain D- and L-interconversions to take place. Factors that affect the requirements for specific amino acids which are particularly pronounced in avian species are summarised in Table 2.3. 

The complexes studied were of the type [Co(en)jaal (aa amino acid anion) using glycine, D- and L-alanine, D- and L-leucine, and D- and L-phenylalanine. The compounds [Co(en) pic](C10 )t (pic picolinate ion) and [Co(NH ) L-palan]Ij (palan s phenylalanine anion) were studied for comparison ... 

The leucine monolayers were also immersed in saturated DL-leucine solutions. As shown in Figure 17, a diffraction peak was observed at 6.34° for both D and L-leucine SAMs. This happens because in the presence of equimolar amounts of D and L enantiomers of leucine, the racemic crystal tends to form instead of either one of the two pure enantiomeric crystals. 

D- and L-leucine have been prepared by amination of n- and u-o-bromoisocaproic acid (296) and by the action of pancreatin on oi/-leudne (846). t/-Leudne has been prepared by the action of P, gUrucim on Di/-leudne (702, 704). n-Leudne has been prepared by the action of n-amino acid oxidase on DL-leudne (766). 

AR Mitchell, SBH Kent, IC Chu, RB Merrifield. Quantitative determination of d-and L-amino acids by reaction with ferf-butoxycarbonyl-L-leucine A-hydroxysuccin-imide ester and chomatographic separation as d,l and l,l dipeptides. Anal Chern 50, 637, 1978. 

Lennernas s group at Uppsala has performed extensive studies to confirm the validity of this in vivo experimental set-up at assessing the rate and the extent of drug absorption. Recovery of PEG 4000 (a non-absorbable marker) is more than 95%, which indicates that the absorption barrier is intact. In addition, maintenance of functional viability of the mucosa during perfusion has been demonstrated by the rapid transmucosal transport of D-glucose and L-leucine. Estimation of absorption half-lives from the measured Pefr agree well with half-lives derived from oral dose studies in humans (i.e. physiologically realistic half-lives). Human Peff estimates are well correlated with the fraction absorbed in humans, and served as the basis for BCS development, and hence the technique is ultimately the benchmark by which other in situ intestinal perfusion techniques are compared. The model has been extensively used to... 

Bacitracin is a mixture of polypeptide antibiotics produced by Bacillus subtilis. As with penicillin, it contains a thiazolidine nucleus attached through L-leucine to a peptide composed of both d- and L-amino acids. However, it does not contain a (3-lactam ring. Bacitracin prevents cell wall synthesis by binding to a lipid pyrophosphate carrier that transports cell wall precursors to the growing cell wall. 

Figure 7.26 The structure of the hepatotoxic cyclic heptapeptide microcystin LR. L-Arginine and L-leucine are variable amino acids. The reactive unsaturated group is indicated by the star. Abbreviations Adda, amino-methoxy-trimethyl-phenyl-decadienoic acid Mdha, methyldehydro-alanine Masp, methyl D-/so-aspartate D-Glu, D-/soglutamate D-Ala, D-alanine.

In more recent investigations, the assumed multienzyme involved in cyclosporin A biosynthesis could be isolated from T. inflatum. A partially purified enzyme fraction was indeed capable of forming enzyme-substrate complexes by thioester linkage. Although de novo synthesis (in vitro) of cyclosporin A has not yet been achieved, the formation of a partial sequence, namely, the diketopiperazine cyclo(DAla-MeLeu), from D-alanine and L-leucine was observed under consumption of ATP and S-adenosyl-L-methio-nine [25]. 

Figure 3 Manufacturing process of AIV. The manufacturing consists of two fermentation steps tylosin fermentation by S. fradiae and tylosin conversion to AIV by S. ther-motolerans. D-Glucose and L-leucine are fed to the culture for the biotransformation.

Pholipeptin was discovered by Ui et al. in 1997 as a novel phosphatidyl inositol speeific phospholipase C (PI-PLC) inhibitor from Pseudomonas sp. Pholipeptin is composed of five residues of D-leucine, two residues of D-serine, D- and L-aspartic acid, L-threonine, L-isoleucine and 3-hydroxydecanoic acid. Pholipeptin inhibits PI-PLC at 7.8pg/ml (IC50) in a non-competitive manner l Absolute configurations of the constituent amino acids were determined by using chiral HPLC without the racemic mixture of aspartic acid. The stereo chemistry of the two aspartie acids was distinguished by biosjmthetic incorporation of C-L-aspartic acid l... 

Once again, the Ghadiri group used the peptide with the leucine zip. Starting from a racemic mixture of the peptide fragments E and N (with 15 and 17 amino acids respectively), homochiral products were preferentially formed in a homochiral selection process in the catalytic self-replication cycle. The initial mixture contained the two peptide fragments, which each consisted of d- and L-amino acids, i.e., a total of four competing molecular species (NL, N°, EL and E°). Thus, four different products could be formed in the condensation reaction TLL, TDD, TLD and TDL. As stated above, TLL and TDD were formed preferentially. The experimental results can be summarized as shown in Fig. 5.8. 

A single report on the resolution of racemic amino acids by TLC has been recently published. The use of silica gel TLC plates impregnated with QN (0.1%), in combination with appropriate mobile phase system, gave a successful enantior-esolution of methionine, alanine, threonine, valine, leucine, and isoleucine. This method combines the simplicity ofTLC technique with a good sensitivity (0.9-3.7 pg) and enantioselectivity (e.g., for methionine, the corresponding Ry values for d- and L-enantiomers were 25 and 50, respectively) [124],... 

The relation between the isotropic I5N chemical shift and the structural parameters of various kinds of synthetic copolypeptides in the solid state have been studied.58,59,61,67 For this, a series of 15N-labelled polypeptides were prepared, [Ala, X] , [Gly, X] and [Leu, X] , consisting of 15N-labelled amino acids (Ala L-alanine, Gly glycine, Leu L-leucine) and other normal amino acids (X natural abundance of 15N), where the following amino acids were selected for the X residue (1) L-alanine, D-alanine and L-leucine, which contain... 

---