Phenylalanine esters

A hexaglycine spacer was attached to the solid support to give a substitution of 0.2 mmol g of dry silica and the excess amino groups were then capped using acetic anhydride. In the next step a selectively cleavable, a-chymotrypsin sensitive, phenylalanine ester (2) was implemented for the release of the products from the solid support under mild conditions. Subsequently it was transformed to (3) followed by reactions with glycosyl transferases to yield (4). Finally, the desired glycopeptide was cleaved from the solid support in high yield by treatment of (4) with a-chymotrypsin (Scheme 10.1). 

The next operation consists in the reconversion of the esters into the amino acids. In the case of the lower boiling fractions, this reconversion is effected by boiling the esters with five to six voluiiies of water under a reflux condenser for six to seven hours, until the alkaline reaction has disappeared in the case of the higher boiling fractions, which contain the esters of aspartic and glutamic acids, the reconversion is effected by boiling with baryta water for one and a half to two hours hydrolysis by water alone only converts these esters into their acid esters. Phenylalanine ester is converted into its hydrochloride by evaporation to dryness with hydrochloric acid. 

Glutamic Acid.—The greater part of the glutamic acid is isolated as hydrochloride before the mixture of amino acids is esterified. It is contained with aspartic acid ester in the aqueous solution after the phenylalanine ester has been extracted by ether, and it is separated from aspartic acid, after hydrolysis by baryta, by conversion into its hydrochloride from this it is obtained by treatment with the calculated quantity of soda to combine with the hydrochloric acid and by crystallisation from water, in which it is soluble with some difficulty. 

Aspartic Acid.—A portion of the aspartic acid, after separation from phenylalanine ester and after hydrolysis by baryta, may separate as barium salt this is the barium salt of racemic aspartic acid. The remainder is isolated, when the glutamic acid has been removed as hydrochloride, by boiling with lead hydroxide and treating with hydrogen sulphide to remove hydrochloric acid and lead respectively, and by crystallising from water. It maybe characterised by conversion into its copper salt, or by analysis, and is estimated by its weight. 

Sie sind Vorstufen auch Fur stereoselektive3 Synthesen von a-Amino-/l-hydroxy-car-bonsauren2 (s. Bd. E5, S. 581). 4-Alkoxycarbonyl-5-aryl-4,5-dihydro-l,3-oxazole IV (R3 oder R4 = Aryl) ergeben bei der katalytischen Hydrierung N-Formyl-phenylalanin-ester z.B.3 ... 

Hatano et al.l39 found that the poly(L-lysine)-Cu(II) complex exerted asymmetrically selective catalysis on the hydrolysis of phenylalanine ester, whereas Cu ions and bis(bipyridyl)Cu had no catalytic activity. The great stability of the intermediate PLL-Cu complex with the D-ester was considered responsible for the catalytic activity. 

Hatano and Nozawa" have observed stereoselective effects in the hydrolysis of d- and l-phenylalanine esters using poly-L-lysinecopper(II) complexes as catalysts and some aspects of the topic have been reviewed.99... 

FIGURE 6 Effect of the concentration of citric acid in methanol on the chiral resolution of phenylalanine and its derivatives on Sumichiral OA-2500(S) CSP ( ) D-phenylalanine, (O) L-phenylalanine, ( ) D- and L-phenylalanine amide and (A) D- and L-phenylalanine ester. (From Ref. 20.)... 

Schacht and coworkers in Belgium201-212 used pellets of a polyphosphazene with both ethyl glycinate and ethyl phenylalanate side groups for the controlled release of the antitumor agent, mitomycin-C. A 100% ethyl glycinato polymer released the drug too rapidly, but mixed-substituent polymers with 50-65% phenylalanine ester released the drug at an optimum rate. 

The methoxyketene 297, coordinated to Cr carbonyl, is formed from methoxy-carbene easily by insertion of CO under irradiation [90]. An ester is formed by the reaction of ketene with alcohol. The aminocarbene complex 298 was prepared from benzamide and converted to phenylalanine ester 300 under irradiation of sunlight in alcohol via ketene 299 [91]. The eight-membered lactone 304 was prepared in high yield by the reaction of the alkyne 301 having the OH group in a tether with Cr carbene without irradiation. The vinylcarbene 302 is formed at first and converted to the vinylketene intermediate 303 as expected. The keto lactone 304 is formed from 303 by intramolecular reaction with the OH group and hydrolysis [92],... 

Rice detoxin A/-Acetyl-t-phenylalanine esters Transesterification nr 9... 

They suggested that at the higher pressures (and therefore higher dielectric constants), the scCHFg was capable of dissolving more displaced water this would affect enantioselectivity if one substrate enantiomer displaces more water from the enzyme pocket than does the other enantiomer (26). They also noted that SCCO2 inhibited the reaction. A -Acetyl-L-phenylalanine esters are used as detoxins in rice production (87). Mori et al. (27) evaluated the effect of SCCHF3 pressure on the esterification of racemic phenylethanol [Eq. (10)] with a lipid-coated lipase ... 

Phenylalanine ester [10] Cleavage a-Chymotrypsin Product after cleavage Carboxylic acid... 

Thermolysin Hydrolysis CO2 aspartic acids + phenylalanine ester 300 bar 20-40 C [58]... 

The established migration of the aryl group in the deamination reaction of phenylalanine ester has been ingeniously utilized in a synthesis of some tropane alkaloids. Thus, treatment of the 3a-tropanyl ester (19) of ( )-phenyl-alanine with nitrous acid affords a separable mixture of atropine (20), the 3a-tropanyl ester (21) of ( + )-3-hydroxy-3-phenylpropionate, apo-atropine (22), and 3a-tropanyl rrans-cinnamate (23). Although not obtained in a pure state the cis-isomer of (23), and littorine (24), were also shown to be present in the product mixture. ... 

A phenylalanine ester, N-benzoyl-0-[N benzoyl - L -phenylalanyl]-L- phenylalaninol (13), was also isolated from this same extract [56]. Silica gel fractions 10 and 11 were further resolved by HPLC as described for the penitrems. Fraction 21 of this separation was chromatographed by normal phase HPLC (Rainin cyanopropyl semipreparative, 5% isopropanol/hexane, flushed with 25% isopropanol/hexane). Fraction 4 yielded phenylalaninol. 

Enamide ester, which is a useful synthetic intermediate for a variety of a-amino acids, can be prepared by means of the HWE reaction in the presence of TMG (3) or DBU [20,21]. In the synthesis of teicoplanin aglycon (80) reported by Evans et al. [22], one of the phenylalanine derivatives 79 was synthesized from the aldehyde 75. HWE reaction of aldehyde 75 with phosphonate 76 using TMG (3) in THF gave (Z)-enamide ester 77 in 99% yield. Asymmetric hydrogenation of 77 catalysed by rhodium(I) complex 78 (1 mol%) gave the phenylalanine ester 79 in 96% with 94% ee (Scheme 7.16). 

Glycyl-l-phenylalanine ester 1-phenylalanyl-glycine ester... 

Prochiral olefins such as the (Z)-a-acetamidocinnamic acid derivatives, MAC and EAC, bind to the rhodium-DIPAMP catalyst to form the diastereomeric olefin complexes A and A shown in Scheme 15.18. Oxidative addition of dihydrogen to each of the diastereom-ers forms diastereomeric hydride complexes B and B, each of which imdergoes migratory insertion to form alkyl hydride complexes C and C. These complexes then undergo reductive elimination to form the amino acid ester products. The stereochemistry of the organic products can be predicted for the two parallel paths, assuming that the addition of occms to the face of the olefin coordinated to Rh. The N-acetyl-(R)-phenylalanine ester would be produced from the olefin adduct A and the (S)-product from A. ... 

Scheme 16.1 Stereoselective hydrolysis of phenylalanine esters in aggregates of mixed surfactants. Z = benzyloxycarbonyl. Courtesy of Wiley-VCH Verlag [10],...

Scheme 4.20 DKR of several phenylalanine esters using salicylaldehydes for racemization.

Phenylalanine esters can be prepared in a single step from a-nitrocinnamates by hydrogenation over 10% palladium on carbon, under acidic conditions. 

Lipases and esterases typically show selectivity toward the alcohol or amine part of a carboxylic acid derivative. Favored acyl groups are simple straight chains like acetate or butyrate. In contrast, proteases show higher specificity for the acyl part of a carboxylic acid derivative. Proteases contain a specificity pocket for the acyl group. For example, subtilisins and chymotrypsin favor ester and amides of phenylalanine esters. Another difference between the enzyme classes is that lipases and esterases catalyze hydrolysis of only esters, whereas proteases catalyze hydrolysis of both amides and esters. Several good books on hydrolases in organic synthesis are available [2-4]. 

Ma S, Shen S, Lee H, Eriksson M, Zeng X, Xu J, Eandrick K, Yee N, Senanayake C, Grinberg N. Mechanistic studies on the chiral recognition of polysaccharide-based chiral stationary phases using liquid chromatography and vibrational circular dichroism. Reversal of elution order of iV-substituted alpha-methyl phenylalanine esters. J. Chromatogr. A 2009 1216 3784-3793. 

N-Chlorination/dehydrochlorination of amino acid esters 310) is the simplest route to a-iminocarboxylic acid esters. With the exception of the leucine derivative, which was obtained as a tautomeric mixture, no enamine could be detected in the products by NMR spectroscopy. Phenylalanine ester yielded the enaminoacid ester exclusively. 

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