Synthesis of L-phenylalanine methyl ester

Mirviss, Stanley B.; Dahod, Samun K.; Empie, Mark W.

doi:10.1021/ie00100a025

Cited by 11 publications

(1 citation statement)

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“…The use of esterases for the enantioselective hydrolysis of chiral amino acid esters is a subject of current interest in the literature (Chen et al, 1986;Mirviss et al, 1990) and is of particular importance for the preparation of (5')phenylalanine from synthetic (R,S)-phenylalanine as an alternative approach to fermentation processes already in use (Aida et al, 1986). The availability of (S)-phe-OH at low cost is critical to the manufacture of the sweet dipeptide (S)-aspartyl-(S)-phenylalanine methyl ester (aspartame), whose production in 1984 had alreadyreached 4000 tons (Meienhofer, 1984) and has since more than doubled.…”

Section: Introductionmentioning

confidence: 99%

Highly Enantioselective Hydrolysis of (R,S)‐Phenylalanine Isopropyl Ester by Subtilisin Carlsberg. Continuous Synthesis of (S) ‐Phenylalanine in a Hollow Fiber/Liquid Membrane Reactor

Ricks

Estrada-Valdes

McLean

et al. 1992

Biotechnology Progress

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The resolution of racemic phenylalanine esters with esterases has been reexamined in relation to the development of a continuous process based on the use of hollow fiber/liquid membrane (SLM) reactors. The requirement for high enantioselectivity was met by phenylalanine isopropyl ester, whose (R)‐enantiomer was found refractory to the action of subtilisin Carlsberg, in water, pH 7.5, at 25 °C. The continuous feeding of (R, S)‐Phe‐O‐iPr‐HCl at 2 mm/h to 0.7 g/L subtilisin resulted in steady‐state reaction conditions that gave (S)‐Phe‐OH of 95% enantiomeric excess (ee) at the theoretical rate. The unreacted (R)‐Phe‐O‐iPr, which permeated out continuously, had 80% ee and was racemized quantitatively by heating with a salicylaldehyde catalyst in refluxing toluene. Doubling the feeding rate (4 mm/h) created excessive accumulation of (R)‐Phe‐O‐iPr in the reactor, which inhibited the enzyme through nonproductive binding, lowering the (S)‐Phe‐OH resolution rate to 68% of the theoretical rate. Similar experiments with (R, S)‐Phe‐OMe‐HCl gave (S)‐Phe‐OH of 9–48% ee, due to the enzymatic hydrolysis of (R)‐Phe‐OMe experienced during the runs. When α‐chymotrypsin was used for the continuous hydrolysis of (R, S)‐Phe‐O‐iPr, the isolated (S)‐Phe‐OH showed 67% ee, indicating that substantial hydrolysis of the (‐R)‐ester had occurred.

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Section: Introductionmentioning

confidence: 99%