Of L-proline

The first step is the manufacture of L-proline tert-butyl ester. L-proline (230 g) is dissolved in a mixture of water (1 ) and 5N sodium hydroxide (400 ml). The solution is chilled in an ice bath, and under vigorous stirring, 5 N sodium hydroxide (460 ml) and benzyloxycarbonyl chloride (340 ml) are added in five equal aliquots during a half-hour period. After one hour stirring at room temperature, the mixture is extracted twice with ether and acidified with concentrated hydrochloric acid. The precipitate Is filtered and dried. Yield is 442 g MP 78°C to 80°C. 

Laxmi, Y.R.S. Iyengar, D.S. Synf/i. Commun., 1997,27,1731 (addition of L-proline to this reaction leads to moderate asymmetric induction). 

However, Marchelli et al. [38], were unable to detect any D-proline when milk formula containing 1-proline was heated in open vessels in a MW oven. Westaway and Gedye [30] showed that very small amounts of D-proline (0.1-0.2%) were produced when an aqueous solution of L-proline was heated under reflux in a MW oven for... 

Table 2.5 Formation of optically active functionalized fS-hydroxy-nitroncs 95 by reaction of aldehydes 93 with activated carbonyl compounds 94 and substituted N -alkyl hydroxylamine hydrochloride in the presence of L-proline as the catalyst...

Aldol-type reactions of nitrones (303) occur with electron-deficient ketones, such as a-keto esters, a, 3-diketones, and trifluoromethyl ketones. These reactions are catalyzed by secondary amines. The use of chiral cyclic amines A1-A7 leads to a-(2-hydroxyalkyl)nitrones (304) in moderate yields and rather high optical purity (Scheme 2.120) (381). The mechanism of the nitrone-aldol reaction of iV-methyl-C-ethyl nitrone with dimethyl ketomalonate in the absence and presence of L- proline has been studied by using density functional theory (DFT) (544). 

In a series of reports between 1991 and 1997 Yamaguchi showed that rubidium salts of L-proline (9) catalysed the conjugate addition of both nitroalkanes [29, 30] andmalonates [31-33] to prochiral a,p-unsaturated carbonyl compounds in up to 88% ee (Scheme 1). Rationalisation of the selectivities observed involved initial formation of an iminium ion between the secondary amine of the catalyst and the a,p-unsaturated carbonyl substrate. Subsequent deprotonation of the nucleophile by the carboxylate and selective delivery using ion pair... 

The most efficient catalyst system for the Morita-Baylis-Hillman reaction of methyl vinyl ketone has been reported by Miller [183, 184], Use of L-proline (58) (10 mol%) in conjunction with the A-methyl imidazole containing hexapeptide 131 (10 mol%) provided an efficient platform for the reaction of 125 with a series of aromatic aldehydes 127 (52-95% yield 45-81% ee) (Scheme 52). Importantly, it was shown that the absolute configuration of the proline catalyst was the major factor in directing the stereochemical outcome of the reaction and not the complex peptide backbone. 

This enzyme [EC 5.1.1.4] catalyzes the interconversion of L-proline and D-proline. See Enzyme Energetics (The... 

On the basis of encouraging work in the development of L-proline-DMSO and L-proline-ionic liquid systems for practical asymmetric aldol reactions, an aldolase antibody 38C2 was evaluated in the ionic liquid [BMIM]PF6 as a reusable aldolase-ionic liquid catalytic system for the aldol synthesis of oc-chloro- 3-hydroxy compounds (288). The biocatalytic process was followed by chemical catalysis using Et3N in the ionic liquid [BMIM]TfO at room temperature, which transformed the oc-chloro-(3-hydroxy compounds to the optically active (70% ee) oc, (3-epoxy carbonyl compounds. The aldolase antibody 38C2-ionic liquid system was also shown to be reusable for Michael additions and the reaction of fluoromethylated imines. 

The condensation of 6-substituted 4-hydroxypyrones with 1-cyclohexenecarboxaldehydes in the presence of L-proline gives the initial 1,2-addition addition product of the pyrone with the aldehydes, followed immediately by a 67t-electrocyclic process to give substituted oxopyrano[4,3-/ ][l]benzopyrans <1997JOC6888>. 

Bycroft and Lee (75CC988) developed this into a general method for the asymmetric synthesis of a-amino acids, wherein the chiral auxiliary (L-proline) could be recovered and recycled. Condensation of L-proline methyl ester with a-keto acids using DCC, followed by a treatment with anhydrous ammonia at room temperature, gave the 3-hydroxypiperazine-2,5-diones with high stereoselectivity (cf. Scheme 79). These could be... 

Scheme 5.34 Chemo-enzymatic production of L-proline from D-proline.

Pyrrolizid-l-one, obtained from the ethyl ester of L-proline (see Section II,E), was condensed with methylenetriphenylphosphorane to give 1-methylenepyrrolizidine, [a] 8 —33°, the IR spectrum of the latter compound was identical with that of the naturally occurring alkaloid. Notwithstanding the partial racemization of the base during... 

An even more convincing argument is provided by the studies (46), results of which are also shown in Fig. 14. Tri-n-butyl amine in dimethyl formamide induces only a slow polymerisation of L-proline NCA whereas the polymerisation of y-ethyl-L-glutamate NCA is very fast under these conditions even if the concentration of the base is reduced by a factor of ten (78, 46). This is a striking observation since proline NCA is an extremely reactive monomer and polymerises very fast on addition of a primary amine. However, addition of 3-methyl hydantoin,... 

A 1-1. Erlenmeyer flask (Note 1) equipped with a magnetic stirrer, and a thermometer is charged with 115 g. (1.0 mole) of L-proline (Note 2) and 500 ml. of dimethyl sulfoxide (Note 3). To the stirred suspension are added simultaneously, over 5 minutes, 115 g. (1.0 mole) of 1,1,3,3-tetramethylguanidine (Note 4) and 214 g. (1.10 moles) of tert-butyl phenyl carbonate (Note 5). The proline dissolves completely within a few minutes in an exothermic reaction, the temperature of which reaches a maximum of 50-52° after 10-15 minutes. After stirring for 3 hours, the clear reaction mixture is transferred to a 6-1. Hcparatory funnel and shaken with 2.2 1. of water and 1.8 1. 

V-/ -methoxyphenyl protected a-imino ethyl glyoxalate 169 in the presence of L-proline as catalyst resulted in the formation of enantioselective p-formyl a-aminoacid derivatives 170 in excellent yields. 

Many relatively specific reagents, particularly a variety of metal complexes, have been developed as an aid to the isolation of individual amino acids. An example is provided by the isolation of L-proline from a gelatine hydrolysate using the chromium complex ammonium rhodanilate ammonium dianiline-... 

Suspend the purified salt in 850 ml of water in a stoppered bottle, add 25 ml of pure pyridine and shake the mixture for 4-5 hours. Remove the insoluble pyridine rhodanilate by filtration and wash it with 100 ml of cold water (2). Combine the pale pink filtrate and washings, and add glacial acetic acid dropwise until the formation of a small pink precipitate is complete. Filter, evaporate the almost colourless filtrate to dryness (rotary evaporator) and suspend the residue in absolute ethanol and re-evaporate twice. Dry the resulting faintly pink crude proline in a vacuum desiccator over silica gel the yield is about 18 g. Recrystallise from the minimum volume of absolute ethanol to obtain 11 g (7.3% based on gelatin) of L-proline, m.p. 218-219 °C (decomp.), [oc]d8 —85.6° (c3.0 in H20). Check the purity of the product by t.l.c. on silica gel using the solvent system butan-l-ol-acetic acid-water, 4 1 1 Rf 0.26 (yellow spot with ninhydrin). 

Benzyloxycarbonyl-L-proline. Dissolve 4.6 g (0.04 mol) of L-proline (Expt 5.186) in 10 ml (0.04 mol) of 4 m sodium hydroxide solution, cool to 0 °C in an ice bath, and add 7.0 g (0.041 mol) of benzyl chloroformate and 10 ml (0.04 mol) of 4 m sodium hydroxide solution alternately and portionwise, with shaking and cooling, during 30 minutes. Allow the mixture to warm to room temperature with intermittent shaking during 1 hour, extract with 2 x 15-ml portions of ether, and acidify the aqueous phase (Congo red) with dilute (1 1) hydrochloric acid. Extract the liberated oil with 4 x 10-ml portions of ether, dry over anhydrous sodium sulphate, and remove the ether to obtain 8.8 g (88%) of benzyloxycarbonyl-L-proline which crystallises slowly. A sample recrystallised from ether-light petroleum (b.p. 40-60 °C) has m.p. 75 °C. 

TABLE 8 Effect of the Structures of L-Proline and D-Proline as Chiral Ligands on the Chiral Resolution of Amino Acids... 

An EPME based on impregnation of 2-hydroxy-3-trimethylammoniop-ropyl-P-cyclodextrin (as chloride salt) solution in a carbon paste was proposed for the assay of L-proline [30]. The linear concentration range for the assay of L-proline is between 5.0 x 10 5 and 1.5 x 10 1 mol/L, with a detection limit of 1.0 x 10-5 mol/L. The average recovery is 99.90% with an RSD of 0.12% (n — 10). The electrode is enantioselective over D-proline. 

EPMEs based on carbon paste impregnated with a-, />- and y-cyclo-dextrins are proposed for the assay of L-proline [31]. Response characteristics showed that the proposed electrodes could be reliably used in the assay of L-proline, with the best enantioselectivity and time-stability exhibited by a-cyclodextrin based EPME. The EPMEs based on the proposed unsubstituted cyclodextrins showed lower detection limits (10 10 magnitude order) than the one previously studied, based on /J-cyclodextrin derivative [30]. The widest linear concentration range is recorded for the y-cyclodextrin based EPME (10 8-10-3mol/L). The recovery tests performed for the assay of L-proline in the presence of d-proline (recoveries higher than 99.65%) proved that the proposed... 

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