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Enzymatic resolution of amino acids via ester hydrolysis

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Summary

The present review outlines recent examples of enzyme-based resolution procedures for amino acids via the hydrolysis of their esters. The resolutions have been achieved by using proteases (α-chymotrypsin, subtilisin and other microbial proteases, and sulfhydryl proteases of plant origin) and lipases. Relevant work utilizing yeast and other microbial cells is also included.

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References

  • Acosta CK, Bahr ML, Burdett JE, Jr, Cessac JW, Martinez RA, Rao PN, Kim HK (1991) Synthesis of unnatural amino acids. J Chem Res (S): 110–111; J Chem Res (M): 0914–0934

  • Alberghina L, Schmid RD, Verger R (eds) (1991) Lipases: structure, mechanism and genetic engineering. VCH, Weinheim

    Google Scholar 

  • Alks V, Keith DD, Sufrin JR (1992) Synthesis of the constrainedl-methionine analog, (Z)-l-2-amino-4-methylthio-3-butenoic acid. Synthesis: 623–625

  • Anantharamaiah GM, Roeske RW (1982) Resolution ofα-methyl amino esters by chymotrypsin. Tetrahedron Lett 23: 3335–3336

    Google Scholar 

  • Ayi AI, Guedj R, Septe B (1995) Enzymatic hydrolysis of methyl 3,3-difluoro-2-amino esters. Synthesis ofD- andl-3,3-difluoro-2-amino acids and their derivatives. J Fluorine Chem 73: 165–169

    Google Scholar 

  • Barrett GC (1985) Resolution of amino acids. In: Barrett GC (ed) Chemistry and biochemistry of the amino acids. Chapman and Hall, London, pp 338–353

    Google Scholar 

  • Bevinakatti HS, Newadkar RV, Banerji AA (1990) Lipase-catalysed enantioselective ring-opening of oxazol-5(4H)-ones coupled with partial in situ racemisation of the less reactive isomer. J Chem Soc, Chem Commun: 1091–1092

  • Bevinakatti HS, Banerji AA, Newadkar RV, Mokashi AA (1992) Enzymatic synthesis of optically active amino acids. Effect of solvent on the enantioselectivity of lipase-catalysed ring-opening of oxazolin-5-ones. Tetrahedron: Asymmetry 3: 1505–1508

    Google Scholar 

  • Cantacuzène D, Pascal F, Guerreiro C (1987) Synthesis of amino acid esters by papain. Tetrahedron 43: 1823–1826

    Google Scholar 

  • Chen C-S, Fujimoto Y, Girdaukas G, Sih CJ (1982) Quantitative analyses of biochemical kinetic resolutions of enantiomers. J Am Chem Soc 104: 7294–7299

    Google Scholar 

  • Chen S-T, Wang K-T, Wong C-H (1986) Chirally selective hydrolysis ofD,l-amino acid esters by alkaline protease. J Chem Soc, Chem Commun: 1514–1516

  • Chen S-T, Chen S-Y, Hsiao S-C, Wang K-T (1991) Kinetic resolution ofN-protected amino acid esters in organic solvents catalyzed by a stable industrial alkaline protease. Biotechnol Lett 13: 773–778

    Google Scholar 

  • Chen S-T, Tsai C-F, Wang K-T (1994a) Resolution ofN-protected amino acid derivatives in supercritical carbon dioxide catalyzed by “alcalase”. Bioorg Med Chem Lett 4: 625–630

    Google Scholar 

  • Chen S-T, Huang W-H, Wang K-T (1994b) Resolution of amino acids in a mixture of 2methyl-2-propanol/water (19:1) catalyzed by alcalase via in situ racemization of one antipode mediated by pyridoxal 5-phosphate. J Org Chem 59: 7580–7581

    Google Scholar 

  • Chenault HK, Dahmer J, Whitesides GM (1989) Kinetic resolution of unnatural and rarely occurring amino acids: enantioselective hydrolysis ofN-acyl amino acids catalyzed by acylase I. J Am Chem Soc 111: 6354–6364

    Google Scholar 

  • Chênevert R, Létourneau M (1986) Enzymatic resolution ofN-acetylp-nitrophenylserinates. Chem Lett: 1151–1154

  • Chênevert R, Létourneau M, Thiboutot S (1990) Resolution ofβ-hydroxy-α-amino acids by the action of proteases on theirN-acyl methyl esters. Can J Chem 68: 960–963

    Google Scholar 

  • Chibata I, Tosa T, Sato T, Mori T (1976) Production of r-amino acids by aminoacylase adsorbed on DEAF-Sephadex. Methods Enzymol 44: 746–759

    PubMed  Google Scholar 

  • Coppola GM, Schuster HF (eds) (1987) Asymmetric synthesis: construction of chiral molecules using amino acids. Wiley, New York

    Google Scholar 

  • Crich JZ, Brieva R, Marquart P, Gu R-L, Flemming S, Sih CJ (1993) Enzymatic asymmetric synthesis ofα-amino acids. Enantioselective cleavage of 4-substituted oxazolin-5ones and thiazolin-5-ones. J Org Chem 58: 3252–3258

    Google Scholar 

  • Csuk R, Glänzer BI (1988) Enantioselective hydrolysis ofN-acetyl-fluoro-phenylalanineethylesters by lyophilised yeast. J Fluorine Chem 39: 99–106

    Google Scholar 

  • De Jersey J, Zerner B (1969) Spontaneous and enzyme-catalyzed hydrolysis of saturated oxazolinones. Biochemistry 8: 1967–1974

    PubMed  Google Scholar 

  • De Jersey J (1970) Specificity of papain. Biochemistry 9: 1761–1767

    PubMed  Google Scholar 

  • Dernoncour R, Azerad R (1987) Enantioselective hydrolysis of 2-(chlorophenoxy)propionic esters by esterases. Tetrahedron Lett 28: 4661–4664

    Google Scholar 

  • Desnuelle P (1972) The lipases. In: Boyer PO (ed) The enzymes, vol 7. Academic Press, New York, p 575

    Google Scholar 

  • Drueckhammer DG, Barbas CF, III, Nozaki K, Wong C-H, Wood CY, Ciufolini MA (1988) Chemoenzymic synthesis of chiral furan derivatives: useful building blocks for optically active structures. J Org Chem 53: 1607–1611

    Google Scholar 

  • Duthaler RO (1994) Recent developments in the stereoselective synthesis ofα-amino acids. Tetrahedron 50: 1539–1650

    Google Scholar 

  • Faber K (1995) Biotransformations in organic chemistry. Springer, Berlin Heidelberg New York Tokyo, p 37

    Google Scholar 

  • Fadnavis NW, Reddy NP, Bhalerao UT (1989) Reverse micelles, an alternative to aqueous medium for microbial reactions: yeast-mediated resolution ofα-amino acids in reverse micelles. J Org Chem 54: 3218–3221

    Google Scholar 

  • Folkers K, Kubiak T, Stepinski J (1984) Improved synthesis and resolution ofβ-(3-pyridyl)-Dl-α-alanine. Int J Peptide Protein Res 24: 197–200

    Google Scholar 

  • Fülling G, Sih CJ (1987) Enzymatic second-order asymmetric hydrolysis of ketorolac esters: in situ racemization. J Am Chem Soc 109: 2845–2846

    Google Scholar 

  • Gais HJ (1995) Hydrolysis and formation of carboxylic acid esters. In: Drauz K, Waldmann H (eds) Enzyme catalysis in organic synthesis. VCH, Weinheim, pp 196–200

    Google Scholar 

  • Gerig JT, Klinkenborg JC (1980) Binding of 5-fluoro-l-tryptophan to human serum albumin. J Am Chem Soc 102: 4267–4268

    Google Scholar 

  • Glänzer BI, Faber K, Griengl H (1987) Enantioselective hydrolyses by baker's yeast-II. Esters ofN-acetyl amino acids. Tetrahedron 43: 771–778

    Google Scholar 

  • Greenstein JP, Winitz M (1961a) Chemistry of the amino acids, vol 1. Wiley, New York, pp 733–735

    Google Scholar 

  • Greenstein JP, Winitz M (1961b) Chemistry of the amino acids, vol 2. Wiley, New York, pp 1753–1767

    Google Scholar 

  • Gu R-L, Lee I-S, Sih CJ (1992) Chemo-enzymatic asymmetric synthesis of amino acids. Enantioselective hydrolyses of 2-phenyl-oxazolin-5-ones. Tetrahedron Lett 33: 1953–1956

    Google Scholar 

  • Hallinan KO, Crout DHG, Errington W (1994) Simple synthesis ofl- andD-vinylglycine (2-aminobut-3-enoic acid) and related amino acids. J Chem Soc, Perkin Trans 1: 3537–3543

    Google Scholar 

  • Hunt S (1985) The non-protein amino acids. In: Barrett GC (ed) Chemistry and biochemistry of the amino acids. Chapman and Hall, London, pp 55–138

    Google Scholar 

  • Imperiali B, Prins TJ, Fisher SL (1993) Chemoenzymatic synthesis of 2-amino-3-(2,2′-bipyridinyl)propanoic acids. J Org Chem 58: 1613–1616

    Google Scholar 

  • Jacobs M, Eliasson M, Uhlen M, Flock J-I (1985) Cloning, sequence, and expression of subtilisin Carlsberg fromBacillus licheni formis. Nucleic Acids Res 13: 8913–8926

    PubMed  Google Scholar 

  • Jones JB, Beck JF (1976) Asymmetric syntheses and resolutions using enzymes. In: Jones JB, Sih CJ, Perlman D (eds) Applications of biochemical systems in organic chemistry. Wiley, New York, p 116

    Google Scholar 

  • Kallwass HKW, Yee C, Blythe TA, McNabb TJ, Rogers EE, Shames SL (1994) Enzymes for the resolution ofα-tertiary-substituted carboxylic acid esters. Bioorg Med Chem 2: 557–566

    PubMed  Google Scholar 

  • Kazlauskas RJ, Weissfloch ANE, Rappaport AT, Cuccia LA (1991) A rule to predict which enantiomer of a secondary alcohol reacts faster in reactions catalyzed by cholesterol esterase, lipase fromPseudomonas cepacia, and lipase fromCandida rugosa. J Org Chem 56: 2656–2665

    Google Scholar 

  • Kullmann W (1987) Enzymatic peptide synthesis. CRC Press, Boca Raton, Florida, pp 50–52

    Google Scholar 

  • Lankiewicz L, Kasprzykowski F, Grzonka Z, Kettmann U, Hermann P (1989) Resolution of racemic amino acids with thermitase. Bioorg Chem 17: 275–280

    Google Scholar 

  • Liu W, Ray P, Benezra SA (1995) Chemo-enzymic synthesis of optically activeα,α-disubstitutedα-amino acids. J Chem Soc, Perkin Trans 1: 553–559

    Google Scholar 

  • Martres M, Gil G, Méou A (1994) Preparation of optically active aziridine carboxylates by lipase-catalyzed alcoholysis. Tetrahedron Lett 35: 8787–8790

    Google Scholar 

  • Miyazawa T, Takitani T, Ueji S, Yamada T, Kuwata S (1988) Optical resolution of unusual amino-acids by lipase-catalysed hydrolysis. J Chem Soc, Chem Commun: 1214–1215

  • Miyazawa T, Iwanaga H, Ueji S, Yamada T, Kuwata S (1989) Porcine pancreatic lipase catalyzed enantioselective hydrolysis of esters ofN-protected unusual amino acids. Chem Lett: 2219–2222

  • Miyazawa T, Mio M, Watanabe Y, Yamada T, Kuwata S (1992a) Lipase-catalyzed transesterification procedure for the resolution of non-protein amino acids. Biotechnol Lett 14: 789–794

    Google Scholar 

  • Miyazawa T, Iwanaga H, Yamada T, Kuwata S (1992b) Optical resolution of unusual amino acids using microbial proteases. Chirality 4: 427–431

    Google Scholar 

  • Miyazawa T, Iwanaga H, Yamada T, Kuwata S (1993) Utilization of proteases for the resolution of non-protein amino acids. Peptide Chemistry 1992: 94–96

    Google Scholar 

  • Miyazawa T, Iwanaga H, Yamada T, Kuwata S (1994) Resolution of non-protein amino acids via the enantioselective hydrolysis of their esters mediated by sulfhydryl proteases. Biotechnol Lett 16: 373–378

    Google Scholar 

  • Miyazawa T (1995) Enzymatic resolution of racemic fluorine-containing amino acids. In: Kukhar' VP, Soloshonok VA (eds) Fluorine-containing amino acids: synthesis and properties. Wiley, Chichester, pp 267–294

    Google Scholar 

  • Miyazawa T, Minowa H, Miyamoto T, Imagawa K, Yanagihara R, Yamada T (1997a) Resolution of non-protein amino acids via microbial protease-catalyzed ester hydrolysis: marked enhancement of enantioselectivity by the use of esters with longer alkyl chains and at low temperature. Tetrahedron: Asymmetry 8: 367–370

    Google Scholar 

  • Miyazawa T, Imagawa K, Yanagihara R, Yamada T (1997b) Marked dependence on temperature of enantioselectivity in theAspergillus oryzae protease-catalyzed hydrolysis of amino acid esters. Biotechnol Tech. 11: 931–933

    Google Scholar 

  • Morgan J, Pinhey JT (1994) Reaction of organolead triacetates with 4-ethoxycarbonyl-2methyloxazol-5-one. The synthesis ofα-aryl andα-vinylN-acetylglycine ethyl esters and their enzymic resolution. Tetrahedron Lett 35: 9625–9628

    Google Scholar 

  • Morihara K (1974) Comparative specificity of microbial proteinases. Adv Enzymol Relat Areas Mol Biol: 179–243

  • Ng-Youn-Chen MC, Serregi AN, Huang Q, Kazlauskas RJ (1994) Kinetic resolution of pipecolic acid using partially-purified lipase fromAspergillus niger. J Org Chem 59: 2075–2081

    Google Scholar 

  • Nielsen B, Fisker H, Ebert B, Madsen U, Curtis DR, Krogsgaard-Larsen P, Hansen JJ (1993) Enzymatic resolution of AMPA by use ofα-chymotrypsin. Bioorg Med Chem Lett 3: 107–114

    Google Scholar 

  • Nomoto M, Narahashi Y, Murakami M (1960) A proteolytic enzyme ofStreptomyces griseus. J Biochem 48: 593–602

    Google Scholar 

  • Phillips RS (1992) Temperature effects on stereochemistry of enzymatic reactions. Enzyme Microb Technol 14: 417–419

    Google Scholar 

  • Phillips RS (1996) Temperature modulation of the stereochemistry of enzymatic catalysis: prospects for exploitation. Trends Biotechnol 14: 13–16

    Google Scholar 

  • Porter J, Dykert J, Rivier J (1987) Synthesis, resolution and characterization of ring substituted phenylalanines and tryptophans. Int J Peptide Protein Res 30:13–21

    Google Scholar 

  • Pugniere M, Domergue N, Castro B, Previero A (1994) Pronase in amino acid technology: optical resolution of nonproteinogenicα-amino acids. Chirality 6: 472–478

    Google Scholar 

  • Rao PN, Burdett JE, Jr, Cessac JW, DiNunno CM, Peterson DM, Kim HK (1987) Synthesis of 3-(3-pyridyl)- and 3-(3-benzo[b]thienyl)-D-alanine. Int J Peptide Protein Res 29: 118–125

    Google Scholar 

  • Ratcliffe SJ, Young GT, Stein RL (1985) 2-Amino-4-(3-pyridyl) butyric acid and related peptides. J Chem Soc, Perkin Trans 1: 1767–1771

    Google Scholar 

  • Roberts DC, Vellaccio F (1983) Unusual amino acids in peptide synthesis. In: Gross E, Meienhofer J (eds) The peptides, vol 5. Academic Press, New York, pp 341–449

    Google Scholar 

  • Roper JM, Bauer DP (1983) Synthesis of phenylalanines in high enantiomeric excess via enzymatic resolution. Synthesis: 1041–1043

  • Schricker B, Thirring K, Berner H (1992)α-Chymotrypsin catalyzed enantioselective hydrolysis of alkenyl-α-amino acid esters. Bioorg Med Chem Lett 2: 387–390

    Google Scholar 

  • Schutt H, Schmidt-Kastner G, Arens A, Preiss M (1985) Preparation of optically activeD-arylglycines for use as side chains for semisynthetic penicillins and cephalosporins using immobilized subtilisins in two-phase systems. Biotechnol Bioeng 27: 420–433

    Google Scholar 

  • Sheardy R, Liotta L, Steinhart E, Champion R, Rinker J, Planutis M, Salinkas J, Boyer T, Carcanague D (1986) The enzymatic resolution of aromatic amino acids. J Chem Educ 63:646–647

    Google Scholar 

  • Solladié-Cavallo A, Schwarz J, Burger V (1994) A four-step, highly enantioselective synthesis and enzymatic resolution of 3,4-dichloro-phenylalanine. Tetrahedron: Asymmetry 5: 1621–1626

    Google Scholar 

  • Tong JH, Petitclerc C, D'lorio A, Benoiton NL (1971) Resolution of ring-substituted phenylalanines by the action ofα-chymotrypsin on their ethyl esters. Can J Biochem 49: 877–881

    PubMed  Google Scholar 

  • Trincone A, Palmieri G, Lama L, Nicolaus B, De Rosa M, Gambacorta A (1990) Kinetic resolution of aminoacid ester with immobilized cells ofSulfolobus solfataricus. Biotechnol Lett 12: 717–720

    Google Scholar 

  • Turner NJ, Winterman JR, McCague R, Parratt JS, Taylor SJC (1995) Synthesis of homochirall,-(S)-tert-leucine via a lipase catalysed dynamic resolution process. Tetrahedron Lett 36: 1113–1116

    Google Scholar 

  • Williams RM (1989) Synthesis of optically activeα-amino acids. Pergamon Press, Oxford

    Google Scholar 

  • Wong C-H, Whitesides GM (1994) Enzymes in synthetic organic chemistry. Pergamon (Elsevier), Oxford, pp 70–108

    Google Scholar 

  • Xie Z-D, Liu L-P, Wu Q, He B-L (1995) Resolution ofDl-phenylalanine by procine pancreas lipase catalyzed transesterification in monophasic organic solvent. Chin Sci Bull 40: 41–44

    Google Scholar 

  • Yamskov A, Tikhonova TV, Davankov VA (1981) Proteases as catalysts of enantioselectiveα-amino ester hydrolysis: 3. Pronase catalysed hydrolysis of methyl esters of leucine, phenylalanine and valine. Enzyme Microb Technol 3: 141–143

    Google Scholar 

  • Yee C, Blythe TA, McNabb TJ, Walts AE (1992) Biocatalytic resolution of tertiary asubstituted carboxylic acid esters: efficient preparation of a quaternary asymmetric carbon center. J Org Chem 57: 3525–3527

    Google Scholar 

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  1. Department of Chemistry, Faculty of Science, Konan University, 658-8501, Higashinada-ku, Kobe, Japan

    T. Miyazawa D.Sc.

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Miyazawa, T. Enzymatic resolution of amino acids via ester hydrolysis. Amino Acids 16, 191–213 (1999). https://doi.org/10.1007/BF01388169

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