L-Norvaline

An alternative to extraction crystallization is used to obtain a desired enantiomer after asymmetric hydrolysis by Evonik Industries. In such a way, L-amino acids for infusion solutions or as intermediates for pharmaceuticals are prepared [35,36]. For example, non-proteinogenic amino acids like L-norvaline or L-norleucine are possible products. The racemic A-acteyl-amino acid is converted by acylase 1 from Aspergillus oryzae to yield the enantiopure L-amino acid, acetic acid and the unconverted substrate (Figure 4.7). The product recovery is achieved by crystallization, benefiting from the low solubility of the product. The product mixture is filtrated by an ultrafiltration membrane and the unconverted acetyl-amino acid is reracemized in a subsequent step. The product yield is 80% and the enantiomeric excess 99.5%. 

Table 1.2. CHEMICAL STRUCTURES OF CYCLOSPORINS A-Z Bmt = (2S, 3R, 4R, 6 -2-amino-3-hydroxy-4-methyl-6-octenoic acid (= (4R)-4-(( )-2-butenyl)-4-methyI-L-threonine) Abu = L-a-aminobuty-ric acid Nva = L-norvaline MeVal = V-methyl-L-valine MeLeu = A -methyl-L-leucine. 

Place 35 kg of L-norvaline in approximately 300 kg of denatured ethanol in a reactor. Introduce approximately 60 kg of thionyl chloride, slowly and gradually. After stirring for a quarter of an hour, heat to reflux for 3 hours and... 

Place 45 kg of ethyl N-norvalinate hydrochloride approximately 110 liters of water in a vessel equipped with a stirrer. Alkalify, then pour 23 kg of pyruvic acid very gradually into the solution obtained previously and stir the reaction mixture for 30 min. Place an aqueous suspension of charcoal containing 5% palladium and the alkaline solution of ethyl L-norvalinate obtained previously in a hydrogenation apparatus. Hydrogenate under pressure (30 bars) at room temperature for approximately one day. Filter under vacuum and evaporate the filtrate under reduced pressure, filter off and dry. Treat the residue obtained with ethanol remove the insoluble material, consisting of sodium chloride, by filtration and rinse it with ethanol. Combine the ethanolic solutions evaporate off the ethanol under reduced pressure and crystallize the residue from acetonitrile 34.3 kg of N-[(S)-l-carbethoxybutyl]-(S)-alanine are obtained, that is a 63.9% yield. 

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. 

Azaserine, 5-diazo-4-oxo-L-norvaline (DONV) and 6-diazo-5-ketonorleucine (DON) are other examples of mechanism-based irreversible inhibitors51). They are stable to nucleophilic attack, but on enzymatic protonation, they are converted to the reactive diazonium ions (30). N-Nitroso compounds have been proposed as irreversible inhibitors of proteolytic enzymes. N-Nitrosolactam (31) can inhibit chymotrypsin... 

L-Leucine, L-valine, L-norvaline, L-methionine, L-phenylalanine, and L-tyrosine were produced by means of the recombinant E. coli cells with high yields (>80%) and high optical purities (up to 100% ee). 

The incubation mixture contained in a Anal volume of 100 /iL 400 fiM DL-homocysteine, 500 (iM ( )-L-A/5-methyltetrahydrofolate, 50 fiM cyanocobalamin, 300 fiM 5-adenosylmethionine, 125 mM 2-mercaptoethanol, 20 fiM L-norvaline, 50 mM potassium phosphate buffer (pH 7.4), and 50 /xL of liver or cell extract. The incubation mixture was immediately flushed with nitrogen and overlayered with 50 /tL of bis(3,5,5-trimethylcyclohexyl)-phthalate. The incubation, carried out at 37°C in the dark, was stopped by the addition of 10 / L of 4 TV perchloric acid. The acid was then neutralized by addition of 10 / L of 4 TV KOH containing 3.3 M potassium bicarbonate. After centrifugation, 90 /iL of supernate was mixed with 175 fiL of o-phthaldialdehyde reagent (prepared by mixing 1 mL of 56 mM o-phthaldialdehyde in methanol with 9 mL of 0.1 M sodium borate buffer, pH 9.5, then adding 40 fiL of 2-mercaptoethanol). After 2 minutes at 23°C, 220 /xL of this mixture was used for HPLC analysis. The assay is linear for at least 2 hours. 

Structure of the Collapsed Monolayers. IR spectra of specimens prepared from air dried collapsed monolayers were typical of specimens in the a-helical conformation with no indication of any p conformation. Electron diffraction patterns gave a similar result. The patterns for poly-(L-leucine) and poly(L-norleucine) are similar to poly(L-norvaline) (12) with low crystallinity. A strong equatorial reflection at 10.94 0.10 A is observed in poly(L-leucine). If we assume as previously (5) that this is the 100 reflection from a hexagonal cell, the calculated area per residue in the monolayer is 17.3 A, assuming the molecular separation is the same as in the collapsed film. This figure is in agreement with the observed area of 16 A in view of the difficulties encountered in spreading the monolayer. 

Simple L-alanine, L-valine, L-norvaline, L-isolecucine, L-serine and other linear amino acids [ 121 ] or chiral amino acids with a binaphthyl backbone [ 122] and peptides have also been used as asymmetric catalysts [123,124,125,126]. Solid-supported proline-terminated peptides have been used for heterogeneous catalysis of the asymmetric aldol reaction [ 127]. Apart from proline and derivatives, other cyclic compounds such as 5,5-dimethyl thiazolidinium-4-car-boxylate (DMTC) [128], 2-fert-butyl-4-benzyl imidazolidinones [129], (l/ ,25)-2-aminocy-clopentanecarboxylic acid [130], (5 -5-(pyrrolidin-2-yl)tetrazole, (5)-l,3-thiazolidine-4-car-boxylic acid, (5)-5,5-dimethyl-l,3-thiazolidine-4-carboxylic acid, and (5)-hydroxyproline are effective catalysts in asymmetric aldol reactions [126,131,132,133,134,135]. 

Fig. 4a. Pathways of hydroxamic acid syntheses of siderophores containing Ns-hydroxyornithine building blocks, a) Starts with e-nitro-L-norvaline. Schemes b) and c) start with ornithine derivatives protected at N5 with CBZ (benzyloxycarbonyl) and Tos (toluenesulfonate), BZL (benzyl), respectively Fig. 4b. Scheme of the synthesis of aerobactin. Protected g-hydroxynorleucine 1 (P = BOC,P = CH3) is transformed into the protected hydroxamic acid 2. Deprotection of the a-NH2 grqup enables alkylation of the o-substituted hydroxamate to give compound 3...

Synonyms (S)-2-Amino-4-methylpentanoic acid 4-Methyl-L-norvaline... 

A recent synthesis of pseudoconhydrine (165) and A-methylpseudoconhydrine (166) utilized an osmium catalyzed asymmetric dihydroxylation of an A-alkenylurethane derived from L-norvaline [438]. 

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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