Phenylalanine reaction scheme

Figure 8.6 Reaction schemes for the production of L-phenylalanine by enzymatic methods.

Consider reaction schemes for the production of L-phenylalanine by enzymatic methods. Now match each of the following substrates with the enzyme(s) responsible for L-phenylalanine formation. 

JOC6261> and peptide isosteres <1995JOC8074>. The A, A -diprotected phenylalaninal 465 (Scheme 119) was obtained from L-phenylalanine 464 in good yield. The reaction of 465 with 2-TST provided the expected a -amino alcohol 466 as a major product. The oxidative removal of the -methoxybenzyl group with cerium ammonium nitrate (CAN, (NH4)2Ce(N03)6) and silylation furnished the compound 467, which was transformed into the aldehyde 468 in excellent yield. 

R) -( + )-phenylalanine to (S)-( + )-amphetamine in 5% overall yield, (R)-( — ) and (S)-( + )-2-amino-l-phenylpropane-3,3,3-d3 (69) has been synthesized57 in 32.8% overall yield, 99% isotopic purity and >99% enantiomeric purity according to the reaction scheme (equation 29) which involves (.R)-3-phenyl-2-(4-toluenesulphamoyl)propyl-l,l-d2 4-toluenesulphonate, CR)-70, and (5)-JV-(l-methyl-d3-2-phenethyl)-4-toluenesulphonamide,... 

The catalysts 11 and 12 (Fig. 4) were used for the synthesis of phenylalanine derivatives (Scheme 7) [28]. Besides the SAPC system, both the homogeneous hydrogenation and the aqueous-biphasic system were investigated. The supported complex 11, like the homogeneous analogue, showed poor performance as far asenantio selectivities are concerned. In contrast, the aqueous-biphasic catalyst performed at least moderately enantioselective. In this context enhanced selectivity was achieved with immobilized catalyst 12. The increased ee values (from 16 to 55%) were obtained at the expense of an extended reaction time, which increased from 2 to 40 h. 

Dialkyl H-phosphonates are used not only for the preparation of N-protected amino acids, but also as active coupling agents in the peptide synthesis [89,115,116], Among a wide variety of methods for the synthesis of peptides, the procedure via mixed carboxylic-phosphoric anhydride-type intermediate has so far attracted attention because this compound plays an important role in the biosynthesis of proteins and peptides [117]. Zhao et al. [89] offer the following reaction scheme for the synthesis of peptides. Phenylalanine and tryptophane are nsed as amino acids. 

Amino acid-derived primary-tertiary diamine catalysts have been used extensively in aldol reactions. Lu and Jiang [34] documented a direct asymmetric aldol reaction between acetone and a-ketoesters catalyzed by an L-serine-derived diamine 17. Sels et al. [35] found that several primary amino acid-based diamines (18) were efficient catalysts for the syn-aldol reaction of linear aliphatic ketones with aromatic aldehydes. Luo and Cheng utilized L-phenylalanine-derived diamine catalyst 15a for the enantioselective syn-aldol reaction of hydroxyl ketones with aromatic aldehydes [36]. Moreover, a highly enantioselective direct cross aldol reaction of alkyl aldehydes and aromatic aldehydes was realized in the presence of 15a (Scheme 3.8) [37]. Very recently, the same group also achieved a highly enantioselective cross-aldol reaction of acetaldehyde [38]. Da and coworkers [39] discovered that catalyst 22, in combination with 2,4-dinitrophenol, provided good activation for the direct asymmetric aldol reaction (Scheme 3.9). 

Reaction scheme for a typical substrate of leucine AmDH (t-ArnDH) (a), phenylalanine AmDH (F-AmDH) (b), and chimeric AmDH (cFLI-AmDH) (c). 

Intermolecular radical reactions have also been reported, including selective radical-radical coupling reactions. These reactions involve the formation of a-amino acid radicals (stabilized by the captodative effect), which can couple to, for example, benzyl radicals to form phenylalanine derivatives (Scheme 21). The benzyl radicals are generated by hydrogen-atom abstraction from toluenes using alkoxyl radicals derived from peroxides and/or aromatic ketone sensitizers. 

Interestingly, though primary amino acids were unable to catalyze the Michael addition to nitrostyrene, their alkahne salts such as hthium phenylalanine were found to be viable catalysts for the reaction (Scheme 5.17) [33a,34],... 

Firooznia has reported the synthesis of 4-substituted phenylalanine derivatives via cross-coupling of protected (4-pinacolylboron)phenylalanine derivatives such as 61 with aryl and alkenyl iodides, bromides and triflates [44]. They have further shown that BOC derivatives of (4-pinacolylboron)phenylalanine ethyl ester 61 or the corresponding boronic acids undergo Suzuki-Miyaura reactions with a number of aryl chlorides in the presence of PdCl2(PCy)3 or NiCl2(dppf), respectively providing diverse sets of 4-substituted phenylalanine derivatives of type 62 [45]. This strategy has also been used for the synthesis of enantiomerically enriched 4-substituted phenylalanine derivatives (Scheme 3.28) [46]. 

The Henry reactions of A, ALdibenzyl-L-phenylalaninal with nitroalkanes using 1.2 equiv of tetrabutylammonium fluoride (TBAF) as the catalyst proceed in ahighly stereoselective manner, as shown in Eqs. 3.82 and 3.83. This reaction provides rapid and stereoselective access to important molecules containing 1,3-diamino-2-hydroxypropyl segments, which are cenhal structural subunit of the HIV protease inhibitor amprenavir (in Scheme 3.21). 

The protease a-chymotrypsin has been used for transesterification reactions by two groups (Entries 7 and 8) [35, 36]. N-Acetyl-l-phenylalanine ethyl ester and N-acetyl-l-tyrosine ethyl ester were transformed into the corresponding propyl esters (Scheme 8.3-2). 

Heteroarylphenylalanines could be smoothly obtained via microwave-promoted Suzuki reaction of heteroaryl halides with 2-amino-3-[4-(dihy-droxyboryl)phenyl]propanoic acid (Scheme 28) [46]. Interestingly, the free amino acid could be used without any protection of the amine and carboxylic acid fimctionahty. When 4-(dihydroxyboryl)-L-phenylalanine was used as organometallic partner no racemization was observed. The carboxylate anion and free amino group seem to shield the a-C - H from deprotonation and thus hmit racemization. 

A similar reaction of A-toluenesulfonyl derivatives of (.S )-alanine, phenylalanine, and valine (188-190) with PhPCl2 gave 4-methyl, benzyl, and isopropyl derivatives of 2-phenyl-1-p-toluenesulfonyl-l, 3,2-oxazaphospholidin-5-one, 191-193 in high yields (Scheme 53) [84], The ratios of the (2.V,4.V)/(2/f,4.V) diastereomers (which were designated as cis/trans isomers) were 1 1, 2 1, and 10 1 for 191a,b, 192a,b, and... 

Asymmetric syntheses of (3- amino acids result from the addition of chiral enolates (399) to nitrone (400) via A-acyloxyiminium ion formation (642, 643). Regioselective convergence is obtained in the reactions of chiral boron- and titanium- enolates (399a,b), (401), and (402). This methodology was used in preparing four stereoisomers of a-methyl- 3-phenylalanine (403) in enantiomeric pure form (Scheme 2.179) (644). 

The enantioselective nitroaldol reaction of phe-nylalaninals 45 with nitromethane was also promoted with the N-anthracenylmethyl ammonium fluorides in the presence of potassium fluoride.1411 Interestingly, as shown in Scheme 16, the major product was the (2R,3S)-isomer 46a when N,N-dibenzyl-(S)-phenylalaninal and 12 (R=benzyl, X=F) were used while the (2S,3S)-isomer 46b was major when N-tert-butoxycarbonyl derivative 45b and 12 (R=allyl, X=Br) together with potassium fluoride were used. The nitroalcohols 46a and 46b were respectively converted to amprenavir 47a, a HIV protease inhibitor, and its diastereomer 47b. The... 

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