Enantioselective Hydrolysis of (R,S)-Naproxen Methyl Ester Using Two-step Acetone-treated Candida rugosa Lipase

2단계 아세톤 침전법으로부터 얻어진 Candida rugosa Lipase를 이용한 (R,S)-Naproxen Ester의 광학선택성 수화반응

  • 이은교 (미생물공정 연구실, 생명공학연구소) ;
  • 최순자 (미생물공정 연구실, 생명공학연구소) ;
  • 정봉현 (미생물공정 연구실, 생명공학연구소)
  • Published : 2000.08.01

Abstract

A novel two-step acetone treatment method was developed to enhance the enantioselectivity of Candida rugosa lipase (CRL) toward the hydrolysis of racemic naproxen methyl ester. The acetone-teated CRL was considerably more enantioselective than the crude CRL, yielding an enantiomeric excess of 98~100%. The crude and acetone-treated CRLs were subjected to anion exchange chromatography, and their chromatography profiles were compared. In consequence, both chromatography profiles were found to be almost identical, resulting in two separate lipase peaks (lipase A and B). The lipase B, which is known to be less enantioselective, was treated with acetone using a two-step treatment method. The enantioselectivity of acetone-treated lipase B was dramatically increased, yielding an enantiomeric excess of 99%.

Keywords

References

  1. Biotechnol. Bioeng. v.38 Enzymatic resolution of (S)-(+)-naproxen in a continuous reactor Battistel, E.;D. Bianchi;P. Cesti;C. Pina
  2. Biotechnol. Lett. v.20 Treatment of Candida rugosa lipase with short-chain polar organic solvents enhances its hydrolytic and synthetic activities Chamorro, S.;J. M. Sanchez-Montero;A. R. Alcantara;J. V. Sinisterra
  3. J. Org. Chem. v.60 A 2-propanol treatment increases the enantioselectivity of Candida rugosa Lipase toward esters of chiral carboxylic acids Colton, I. J.;S. N. Ahmed;R. J. Kazlauskas
  4. Tetrahedron v.45 A Stereoconvergent strategy for the synthesis of enatiomerically pure(R)-(-) and (S)-(+)-2-(6-methoxy-2-naphthyl)-propionic acid (naproxen) Giordano, C.;G. Castaldi
  5. Drugs v.52 Chirality and nonsteroidal anti-inflammatory drugs Hayball, P. J.
  6. Kor. J. Biotechnol. Bioeng. v.14 Candida rugosa lipase-catalyzed production of optically pure S-(+)-ketoprofen Kim, M. G.;S. J. Choi;W. A. Choi;C. H. Kim;B. H. Chung
  7. Enz. Microb. Technol. v.22 Enantiose-lectivity of Pesudomonas cepacia and Candida rugosa lipases for the resolution of secondary alcohols: The effect of Candida rugosa isoenzymes Lundell, K.;T. Raijola;L. T. Kanerva
  8. Enz. Microb. Technol. v.15 Enzymes in the synthesis of chiral drugs Margolin, A. L.
  9. Drugs v.52 Preclinical and clinical development of dexketoprofen Mauleon, D.;R. Artigas;M. L. Garcia;G. Carganico
  10. Biotechnol. Lett. v.11 Characterization of three distinct forms of lipolytic enzyme in a commercial Candida rugosa lipase preparation Shaw, J. F.;C. H. Chang
  11. J. Chem. Tech. Biotechnol. v.67 Chirotechnology: Designing economic chiral syntheses Sheldon, R. A.
  12. Biotechnol. Letts v.11 Detection and partial purification of two lipases from Candida rugosa Veeraragavan, K.;B. F. Gibbs
  13. J. Am. Chem. Soc. v.112 Enhancing the enantioselectivity of Candida Lipase catalyzed ester hydrolysis via noncovalent enzyme modification Wu, S. H.;Z. W. Guo;C. J. Sih