Valine methyl ester

Enantiomer separation factors (a values) for valine and phenylalanine as well as their esters of 5-10 for phenylalanine and 4-10 for valine have been shown at the 0.1-1 g ChiraLig scale. These a values vary as a function of solvent and other loading matrix factors (pH, salts, etc.). However, all of these cases show a values high enough to obtain reasonable enantiometric purity in less than or equal to three stages. The system with a value of = 6 for the valine methyl ester enantiomers has the ability to load the valine onto the resin in H,0 containing LiClO and also to... 

C12H21N 773777-37-4) see Dicycloverine 2 -cyanobiphenyl-4-carboxaldehyde (C14Hc.NO 135689-93-9) see Valsartan 7V-[(2 -cyano[l,l -biphenyl]-4-yl)methyl]-L-valine methyl ester... 

A -[(4-nitrophenoxy)carbonyI]-L-valine methyl ester (Ci HijNiOs 162537-10-2) see Ritonavir ( )-l-(4-nitrophenoxy)-2-hydroxy-3-(tcrt-butylamino)-propane... 

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. 

Figure 5. Top Tetraurea calixarene monomers 37 and 38 bearing chiral amino acid ester residues (isoleucine and valine methyl esters, respectively) attached to the urea functions. Norcamphor 39 was the chiral guest used to detect the chirality transfer from the outside to the inner cavity.

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... 

Except in the case of the complex of [284] with valine methyl ester the 55-l or RR-d complexes are the most stable... 

The synthesis of valsartan (2) by Novartis/Ciba-Geigy chemists is highlighted in Scheme 9.5. Biphenylbenzyl bromide 18 is converted to biphenyl acetate 19 in the presence of sodium acetate in acetic acid. Hydrolysis of 19 followed by Swern oxidation delivered the biphenyl aldehyde 20, which underwent reductive amination with (L)-valine methyl ester (21) to give biphenyl amino acid 22. Acylation of 22 with penta-noyl chloride (23) afforded biphenyl nitrile 24, which is reacted with tributyltin azide to form the tetrazole followed by ester hydrolysis and acidihcation to provide valsartan (2). [See Biihlmayer et al. (1994, 1995).]... 

High stereoselectivities (94-100 %) are attained in the reduction of aromatic ketones by use of a new chiral borane complex with (S)-2-amino-3-methyl-l,l-diphenylbutan-l-ol,(S-68) readily prepared in two steps from (S)-valine, in an experimentally convenient procedure961. (S)-Valine methyl ester hydrochloride was converted with excess of phenylmagnesium bromide into (S-68). The same treatment of (R)-valine gave (R-68). In a typical asymmetric reduction the reagent, prepared from (S-68) and borane, and the ketone (69) in tetrahydrofuran were kept at 30 °C for some hours. The corresponding alcohols were obtained in high optical purity. (S-68) could be recovered to more than 80% without racemization 96). 

The utility of the method was demonstrated with a variety of electron-rich and electron-poor aryl aldehydes, but the method was not suitable for aliphatic aldehydes. No racemization was observed in the copper-catalyzed oxidative amidation reaction when an optically active amine, (S)-valine methyl ester, was employed. 

A-f2- 5-f(/ /.S )-l-Carbamoyl-2-phenylethyl]-2,3,6,7-tetrahydro-2-oxo-l/f-azepin-l-yl)-3-methylbutan-oyl]valine Methyl Ester (39) ... 

V- 2-f2,3,6,7-Tetrahydro-2-oxo-5- (i /S)-2-phenyl-l-f(serinylalaninylalaninyl)amino]ethyl)-l//-azepin-l-yl]-3-methylbutanoyl valine Methyl Ester (44) ... 

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. 

Applying mild extraction methods to the mycelium of an ergo-cristine producing Claviceps purpurea strain, an unstable peptide alkaloid of a new type was recently detected (17). Its physical data and chemical transformations contributed to the elucidation of its structure. The fast methanolysis of the new alkaloid led to the well-known N-lysergyl-L-valine methyl ester (18) and L-phenylalanine-D-proline lactam. An amino acid analysis showed the presence of one mole each of valine, phenylalanine, and proline. Thus the new alkaloid has been characterized as iV-[AT-(d-lysergyl)-L-valyl]-L-phenylalanyl-D-proline lactam (18 C35H39N504 mp 235° [a]D +5° in chloroform). 

Various circumstances indicate that 18 and related hitherto overlooked substances (19) are widespread in Claviceps strains. Therefore, it seems very probable that V-lysergyl-L-valine methyl ester, claimed to be a genuine ergot alkaloid (18), is an artefact arising from methanolysis during extraction. 

A hypothetical sequence, based mainly on the reported isolation of cMvsergyl-L-valine methyl ester from rye ergot (18) was proposed by Agurell (58). According to him, the biogenesis of ergotamine (68) can be represented as follows ... 

Valine methyl ester, (S)-, hydrochloride Benzyl chloroformate Palladium hydroxide... 

To a 5 L 3-neck round bottom flask was added the crude carbonylbenzyloxy-3-aminopropanal (115 g, 0.555 mol) followed by addition of water (400 mL) and methanol (1600 mL). The reaction mixture was maintained at 25°C throughout the course of the reaction. After the solution became homogeneous. (S)-Valine methyl ester hydrochloride (90.2 g, 0.538 mol) was added in one portion followed by rapid addition of sodium acetate trihydrate (151 g, 1.11 mol) and sodium cycanoborohydride (73.2 g, 1.17 mol). The reaction mixture was allowed to stir at room temperature for 0.5 hour and was concentrated in vacuo. To this solution, saturated aq sodium bicarbonate (400 mL) was added and the mixture was extracted with isopropyl acetate (1 L). The organic layer was washed with water, dried over sodium sulfate, and concentrated to yield 150 g of crude product, which was dissolved in isopropyl acetate (300 mL) and heptane (2400 mL). Dry HCI was bubbled in and an oily solid precipitated out of solution. The liquid was decanted away from and the solid was dissolved in dichloromethane (3 L). The solution was washed with water (600 mL) and saturated aq sodium bicarbonate (600 mL) and dried over sodium sulfate. It was concentrated in vacuo to yield 105 g (59%) of N-(N-(benzyloxycarbonyl-3-amino)-propyl)valine methyl ester as a light yellow oil. 

To a 3 L flask was added N-(N-(benzyloxycarbonyl-3-amino)-propyl)valine methyl ester (120 g, 0.372 mol) and methanol (1 L). This solution was allowed to stir in the presence of Raney Nickel (180 g) for 1 h. After removal of Raney Nickel by filtration, Pd(OH)2 (24 g) was added and the solution was allowed to stir under 60 psi of a hydrogen atmosphere for 12 h. The solution was purged with nitrogen and repressurized with 60 psi of hydrogen for an additional 1 h. The solution was filtered and concentrated to give 63 g of N-(3-amino)-propyl)valine methyl ester as an an oil (90%). To this oil toluene (120 mL) was added and the solution was again concentrated in vacuo to give the desired product. 

To a 5 L 3-neck round bottom flask with stir bar was added the crude N-(3-amino)-propyl)valine methyl ester (150 g, 0.8 mol) and dichloromethane (3.2 L). Carbonyldiimidazole (232 g, 1.44 mol) was added slowly in portions over 25 min. The solution was allowed to stir at ambient temperature for 40 hours. Water (200 mL) was added over 1 h with stirring until no more gas evolution occurred. A solution of 35% HCI was slowly added to the stirring solution until the solution became acidic. The solution was then partitioned and was washed with water. The organic layer was dried over sodium sulfate and was concentrated to yield 126 g (74%) of 2S-(l-tetrahydro-pyrimid-2-onyl)-3-methyl butanoic acid methyl ester as a colorless solid. 

N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine methyl ester. 

A solution of 15.7 g (92 mmol) of 2-isopropyl-4-(((N-methyl)amino)-methyl)thiazole in 200 ml of THF was combined with a solution of 20.5 g (69 mmol) of N-(((4-nitrophenyl)oxy)carbonyl)-L-valine methyl ester. The resulting solution was treated with 1.6 g of 4-dimethylaminopyridine and 12.9 ml (92 mmol) of triethylamine, heated at reflux for 2 h, allowed to cool, and concentrated in vacuo. The residue was taken up in CH2CI2, washed extensively with 5% aqueous K2C03, dried over Na2S04, and concentrated in vacuo. The resulting product mixture was purified by silica gel chromatography using chloroform as an eluent to provide 16.3 g (54%) of the desired compound. 

L)-Valine methyl ester hydrochloride 2 -Cyanobiphenyl-4-carbaldehyde Sodium cyanoborohydride... 

S)-N-(l-Carboxy-2-methyl-prop-l-yl)-N-pentanoyl-N-[2 -(lH-tetrazol-5-yl)biphenyl-4-ylmethyl]-amine. The product can be prepared starting from 1.40 g of N-valeryl-N-[(2 -cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester and 2.25 g of tributyltin azide with subsequent flash chromatography melting interval 105°-115°C (from ethyl acetate). 

Mycosporine-2 is a fungal metabolite of Botrytis cinerea, and is formulated as the pyrrolidone (5) on mass and 13C and H n.m.r. spectral evidence.9 The marine sponge Dysidea herbacea secretes a chlorine-containing pyrrolinone dysidine, formulated as (6) as a consequence of degradative and spectroscopic studies. Its relative and absolute configurations were settled by X-ray diffraction methods.10 On exposure to strong base the compound is degraded to the pyrrolinone (7), which was synthesized from L-valine methyl ester, and the acid (8), identified by its mass and n.m.r. spectral behaviour.10... 

Aldimines react with allyl bromide in the presence of metallic bismuth and tetrabutylammonium bromide in acetonitrile to give homoallyl amines (Equation (42)).77 When a chiral imine derived from benzaldehyde and (S)-valine methyl ester is used as the substrate, the allylation with allylic bismuth(m) species takes place smoothly by the assistance of a Lewis acid such as BF3-OEt2 and A1C13 to afford a chiral homoallylic amine with high diastereoselec-tivity (Equation (43)).78... 

---