Acetyl-L-phenylalanine methyl ester

The Fijian undescribed Jaspidae sponge which yielded the bengamides and bengazoles contained a diketopiperazine cyc/o-(4-hydroxyprolinyl)L-phenylalanine (335) along with W-acetyl-L-phenylalanine methyl ester (336). The configuration of all of the constituent amino acids was shown to... 

A -acetyl-L-phenylalanine methyl ester -i- H O = AZ-acetyl-L-phenylalanine -i-methanol 5.88-102 3.4.21.1 293.15 5.5 ... 

One way to approach this problem would be through the use of simple model substrates for the enzyme a-chymotrypsin. In this regard, Hein and Nieman (101) first attempted the elucidation of the conformation of well-selected chymotrypsin-bound substrates by using a conformationally constrained molecule as a model for the active conformation of a typical open-chain substrate, AT-acetyl L-phenylalanine methyl ester (l-APME). For... 

Although, a-chymotrypsin is sterospecific toward the L-isomer of most amino acid substrates, Niemann showed that the stereospecificity is reversed in the case of KCTI. The D-isomer of this conformationally restricted ester is hydrolyzed at a rate comparable to that of N-acetylated L-phenylalanine methyl esters while the L-isomer is hydrolyzed very slowly. Hein and Niemann (101,102) pointed out that this anomaly is consistent with a requirement for the carboxylate group of d-KCTI to be in an axial conformation, a conformation which matches a probable conformation of open-chain l-amino acid ester substrates. 

There are numerous examples of enantioselective hydrolyses of the types described in Schemes 3.2 and 3.3, catalysed by lipases and esterases. The selective hydrolysis of amino acid derivatives has been an important part of this field of study. For example, the hydrolase enzyme a-chymotrypsin catalyses the enantioselective hydrolysis of JV-acetyl-DL-phenylalanine methyl ester (5) to give optically pure (L)-acid (6) in 40% yield (Scheme 3.4). The lipase from the fungus Candida cylindracea (ccl) has been shown to hydrolyse octyl 2-chloropropionate (7) with high stereoselectivity on a large scale, giving the (/ )-acid (8) in 46% yield (96% e.e.) and the (S)-ester (45% yield) (Scheme 3.5). 

W-Acetyl-L-phenylalanine, ethyl ester A/-Acetyl-/.-phenylalanine. methyl ester... 

A/- -toluene su1fony1)-T-phenylalanine (62), L-histidine methyl ester (63), A/-acetyl L-valine /-butyl amide (64), etc, are used as chiral addends. 

Volatile peptide derivatives, for instance trifluoroacetyl-L-valyl-L-valine methyl ester or benzyloxycarbonyl-L-leucyl-L-phenylalanyl-L-valine tert.butyl ester can be separated from their diastereoisomers that contain a D-residue by vapor phase chromatography. Also, through the examination of nmr spectra of relatively simple peptides the extent of racemization that occured during their preparation can be determined without separation of the diastereoisomers, because the difference in the chemical shifts of some selected resonances is sufficient for integration. Thus the areas under the well separated peaks of the alanine methyl protons in acetyl-L-phenylalanyl-L-alanine methyl ester and in acetyl-D-phenylalanyl-L-alanine methyl ester can be integrated and the values used to determine the extent of racemization of the phenylalanine residue during coupling. 

Phenylalanine, a key intermediate in the preparation of the sweetener aspartame (the methyl ester of L-phenylalanine/T-aspartic acid dipeptide) [18, 19] may be prepared similarly according to eq. (10). Amidocarbonylation of phenylacetaldehyde, obtainable from styrene, affords A-acetyl-/9-phenylalanine in 72 mol % yield and with > 98 % cobalt recovery [20]. 

Kawabata et al. [28] resolved methyl ( )-Ar-(Boc-Z,-phenylalanyl)-m-2-aminocyclopentanecarboxylate by fractional crystallization from ethyl acetate. The phenylalanine derivative was prepared from the methyl ester of racemic m-2-ACPC (11) by acetylation with JV-Boc-Z.-phenylalanine using l-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC). Edman degradation of the separated isomers, followed by deprotection, acid hydrolysis and desalting with anion-exchange resin, gave enantiomerically pure (15,2/ )- and (l/ ,2S)-2-ACPC. The absolute configurations were proved by X-ray diffraction of the /.-phenylalanine derivatives [28]. 

Fig. 19. Michaelis-Menten constant f Al-acetyl-L-amino add methyl esters with a-chymotrypsin versus the effluent volume of the amino acid from a cation-exchange resin [72]. 1, glydne 2, alanine 3, aminoisobutyric acid 4, valine S, methionine 6, leucine 7, tyrosine 8, phenylalanine.

The methyl ester 25a was found to extract iV-acetyl alanine/phenylalanine carboxylates from aqueous solution into chloroform with l d selectivities o/10 l, while the lipophilic analogue 2Sb transported /V-acetyl phenylalanine through apolar solvent barriers in up to 70% e.e. - ... 

Oi et al. [725] studied the retention of six amino acids (alanine, valine, leucine, methionine, phenylglycine, and phenylalanine) as their A -acetyl methyl esters and A -(3,5-dinitrobenzoyl) derivatives on an (/ )- or (iS)-l-(a-naphthyl)ethylamine stationary phase (2 = 230 nm or 254 nm). Capacity factors and a values are tabulated for all pairs of amino acid derivatives. A 40/10/1, a 100/20/1, or a 200/20/1 hexane/1,2-dichloroethane/ethanol mobile phase was used to generate the separation. 

Cyclobis(N-methyl-L-phenylalanyl), 42B, 358 N-Acetyl L phenylalanyl-L-tyrosine, 39B, 365 Carbobenzoxy-L-leucyl-p-nitrophenyl ester, 40B, 462 6, L-Threonyl-L-phenylalanine-p-nitrobenzyl ester hydro-bromide, 34B, 274... 

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