D-norvaline

Thus we designed and synthesized a bicyclic pyridoxamine derivative carrying an oriented catalytic side arm (16) [11], Rates for conversion of the ketimine Schiff base into the aldimine, formed with 26 (below) and a-ketovaleric acid, indolepyruvic acid, or pyruvic acid, were enhanced 20-30 times relative to those carried out in the presence of the corresponding pyridoxamine derivatives without the catalytic side arm. With a-ketovaleric acid, 16 underwent transamination to afford D-norvaline with 90% ee. The formation of tryptophan and alanine from indolepyruvic acid and pyruvic acid, respectively, showed a similar preference. A control compound (17), with a propylthio group at the same stereochemical position as the aminothiol side arm in 16, produced a 1.5 1 excess of L-norvaline, in contrast to the large preference for D-amino acids with 16. Therefore, extremely preferential protonation seems to take place on the si face when the catalytic side arm is present as in 16. 

PC, D-phenylglycine ABA, D-aminobutyric acid PA, d-phenylalanine NVA, D-norvaline NLEU, o-norleucine MET, D-methionine LEU, D-leucine. Reactions were performed in triplicate and error bars represent the standard error from the mean. 

In the kinetic resolution of amino acid amides with the use of amidases, such as DAP and DaaA, it is possible to synthesize D-amino acids by kinetic resolution, selectively from racemic acid amides [16]. An Escherichia coli transformant highly expressing DAP catalyzed the synthesis of 2.5M (about 220g/l) D-alanine from 5M racemic alanine amide in a 4.5-h reaction, d-2-Amino butyric acid, D-methionine, D-norvaline, and D-norleucine were S5mthesized in a similar manner. We have been successful in the evolution of DAP [17] and DaaA by mutations [18]. 

The asymmetric synthesis of o-amino acids is carried out by an (R)-selective co-transaminase [87]. Several achiral ketones were examined, leading to D-configured amino acids like o-homoalanine, o-serine, o-fluoroalanine, D-alanine, and D-norvaline. A reaction yield of >99% and enanfiopurify of >99.7% were achieved, excepf for D-norvaline. Remarkably, no producf inhibifion by acetophenone was observed at... 

Fig. 2-5. Examples showing the eomplementary separations on glyeopeptide CSPs. (A) Separation of N-CBZ-norvaline on vaneomyein (left) and teieoplanin (right). The mobile phase was methanol 1 % triethylammonium aeetate (20/80 v/v) pH 4.1. (B) Separation of warfarin on teieoplanin (left) and vaneomyein (right) CSPs. The mobile phase was aeetonitrile 1 % triethylammonium aeetate (10/90 v/v) pH 4.1. (C) Separation of naproxen on teieoplanin (left) and ristoeetin A (right). The mobile phase was methanol 0.1 % triethylammonium aeetate (30/70 v/v) pH 4.1. All eolumns were 250 x 4.6 mm i.d. The flow rate for all the separations was 1 mL min at ambient temperature (23 °C).

Fig. S6. Separation of D,L-dansyl amino acids. Conditions 0.65 oiAf L 2>isopropyl-dien-Zn(II) 0.17 A NH,Ac to pH 9.0 with aqueous NI 35/65 CH,CN/H,0 T - 30 flowrate 2 tnl/min column 15 cm by 4.6 mm i.d. S iun Hypersil C solutes CySO H -cysteic acid Ser - serine Trp - tryptophan thr - threonine Norval - norvaline Leu w leucine Norleu - norleucine Phe phenylalanine. Detection at 254 nm. Reprinted with permission from LePage ef at. C246), Am/. Chem. Copyright 1979 by the American Chemical Society.

Sendzik, M. Guamieri, W. Hoppe, D. Monocarbamates derived from (S)-2-(dibenzylami-no) butane-1,4-diol and the influence of the second O-protecting group on the regioselec-tivity of deprotonation. Application to the synthesis of the Boletus toxin (2S,4S)-y-hydroxy-norvaline. Synthesis 1998, 1287-1297. 

Figure 6.8 Experimental variation of the retention of 23 phenylthiohydantoin (PTH) derivatives of amino acids with mobile phase composition in RPLC. Mobile phase mixtures of acetonitrile and 0.05M aqueous sodium nitrate buffer (pH — 5.81). All mobile phases contain 3% THF. Stationary phase ODS silica. Solutes D = aspartic acid C-OH = cysteic acid E = glutamic acid N = asparagine S = serine T = threonine G = glycine H = histidine Q = glutamine R = arginine A = alanine METS = methionine sulphone ABA = a-aminobutyric acid Y = tyrosine P = proline V = valine M = methionine NV = norvaline I = isoleucine F = phenylalanine L = leucine W = tryptophan K = lysine. Figure taken from ref. [610]. Reprinted with permission.

The N-acetyl-D,L-amino acid precursors are conveniently accessible through either acetylation of D,L-amino acids with acetyl chloride or acetic anhydride in a Schotten-Baumann reaction or via amidocarbonylation I801. For the acylase reaction, Co2+ as metal effector is added to yield an increased operational stability of the enzyme. The unconverted acetyl-D-methionine is racemized by acetic anhydride in alkali, and the racemic acetyl-D,L-methionine is reused. The racemization can also be carried out in a molten bath or by an acetyl amino acid racemase. Product recovery of L-methionine is achieved by crystallization, because L-methionine is much less soluble than the acetyl substrate. The production is carried out in a continuously operated stirred tank reactor. A polyamide ultrafiltration membrane with a cutoff of 10 kDa retains the enzyme, thus decoupling the residence times of catalyst and reactants. L-methionine is produced with an ee > 99.5 % and a yield of 80% with a capacity of > 3001 a-1. At Degussa, several proteinogenic and non-proteinogenic amino acids are produced in the same way e.g. L-alanine, L-phenylalanine, a-amino butyric acid, L-valine, l-norvaline and L-homophenylalanine. 

D-valine, A-methyl-L-valine, L-norvaline, L-y-formylmethylnorvaline L-ornithine, n-ornithine, IV-hydroxy-L-ornithine L-Ianthionine, 3-methyl-L-lanthionine... 

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