ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Bioconjugate Chem. 1999, 10, 1, 150-154
RETURN TO ISSUEPREVTechnical Note

Enzyme-Assisted Synthesis and Structural Characterization of Nitrocatechol Glucuronides

View Author Information
Department of Pharmacy, Division of Pharmaceutical Chemistry, POB 56, FIN-00014, University of Helsinki, Finland, Institute of Biotechnology, NMR Laboratory, FIN-00014, University of Helsinki, Finland, Orion Corporation, Orion Pharma, POB 65, FIN-02101 Espoo, Finland, and Finnish Institute of Occupational Health, FIN-00250 Helsinki, Finland
Cite this: Bioconjugate Chem. 1999, 10, 1, 150–154
Publication Date (Web):December 31, 1998
https://doi.org/10.1021/bc980064n
Copyright © 1999 American Chemical Society
Request reuse permissions

    Article Views

    320

    Altmetric

    -

    Citations

    31
    LEARN ABOUT THESE METRICS
    Read OnlinePDF (83 KB)
    Get e-Alerts
    SUBJECTS:

    Abstract

    Enzyme-assisted synthesis and characterization are described for 3-O-β-d-glucuronides 1b−4b of the aglycons E- and Z-2-cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide (entacapone), 1a and 2a, respectively, 3-(3,4-dihydroxy-5-nitrobenzylidene)-2,4-pentanedione (nitecapone) 3a and 4‘-methyl-3,4-dihydroxy-5-nitrobenzophenone (tolcapone) 4a, and 1-o- and 2-o-glucuronides 5b and 6b of the aglycon 1,2-dihydroxy-4-nitrobenzene 5a. Liver microsomes from rats pretreated with Aroclor 1254 were used as catalyst in the synthesis. Glucuronidation was regio- and stereoselective in the case of 1a−4a; only one product was observed by HPLC, HPTLC, and NMR. The glucuronidation of 1,2-dihydroxy-4-nitrobenzene 5a resulted in equal amounts of 1-O-β-d- and 2-O-β-d-glucuronides. Purification of the crude products by C18 solid-phase extraction and/or flash chromatography gave compounds 1b−6b in 38−98% yields (50−84 mg). The structures of the glucuronides were characterized on the basis of UV and IR spectra and confirmed with FAB-MS and NMR spectroscopy.

    †

     Department of Pharmacy.

    ‡

     Institute of Biotechnology.

    §

     Orion Corporation.

    ‖

     Finnish Institute of Occupational Health.

    *

     To whom correspondence should be addressed. Phone:  358 9 70859191. Fax:  358 9 70859556. E-mail:  Jyrki.Taskinen@ helsinki.fi.

    Cited By

    This article is cited by 31 publications.

    1. Jinda Fan, Sarah M. Brown, Zhude Tu, and Evan D. Kharasch . Chemical and Enzyme-Assisted Syntheses of Norbuprenorphine-3-β-d-glucuronide. Bioconjugate Chemistry 2011, 22 (4) , 752-758. https://doi.org/10.1021/bc100550u
    2. Tiia Kuuranne, Mikko Vahermo, Antti Leinonen, Risto Kostiainen. Electrospray and atmospheric pressure chemical ionization tandem mass spectrometric behavior of eight anabolic steroid glucuronides. Journal of the American Society for Mass Spectrometry 2000, 11 (8) , 722-730. https://doi.org/10.1016/S1044-0305(00)00135-5
    3. Helena Keski-Hynnilä, Leena Luukkanen, Jyrki Taskinen, Risto Kostiainen. Mass spectrometric and tandem mass spectrometric behavior of nitrocatechol glucuronides: A comparison of atmospheric pressure chemical ionization and electrospray ionization. Journal of the American Society for Mass Spectrometry 1999, 10 (6) , 537-545. https://doi.org/10.1016/S1044-0305(99)00021-5
    4. Johanna Troberg, Erkka Järvinen, Maria Muniz, Nina Sneitz, Johanna Mosorin, Marja Hagström, Moshe Finel. Dog UDP-Glucuronosyltransferase Enzymes of Subfamily 1A: Cloning, Expression, and Activity. Drug Metabolism and Disposition 2015, 43 (1) , 107-118. https://doi.org/10.1124/dmd.114.059303
    5. Nenad Manevski, Johanna Troberg, Paolo Svaluto-Moreolo, Klaudyna Dziedzic, Jari Yli-Kauhaluoma, Moshe Finel, . Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent. PLoS ONE 2013, 8 (1) , e54767. https://doi.org/10.1371/journal.pone.0054767
    6. Andrew V. Stachulski, Xiaoli Meng. Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides. Natural Product Reports 2013, 30 (6) , 806. https://doi.org/10.1039/c3np70003h
    7. Nenad Manevski, Paolo Svaluto Moreolo, Jari Yli-Kauhaluoma, Moshe Finel. Bovine Serum Albumin Decreases K m Values of Human UDP-Glucuronosyltransferases 1A9 and 2B7 and Increases V max Values of UGT1A9. Drug Metabolism and Disposition 2011, 39 (11) , 2117-2129. https://doi.org/10.1124/dmd.111.041418
    8. Feray Koçan, Ugur Avcıbaşı, Perihan Ünak, Fazilet Zümrüt Biber Müftüler, Çigdem A. İçhedef, Hasan Demiroğlu, Fikriye G. Gümüşer. Metabolic Comparison of Radiolabeled Bleomycin and Bleomycin-Glucuronide Labeled with 99m Tc. Cancer Biotherapy and Radiopharmaceuticals 2011, 26 (5) , 573-584. https://doi.org/10.1089/cbr.2011.0998
    9. Takuji Shoda, Kiyoshi Fukuhara, Yukihiro Goda, Haruhiro Okuda. Enzyme‐assisted synthesis of the glucuronide conjugate of psilocin, an hallucinogenic component of magic mushrooms. Drug Testing and Analysis 2011, 3 (9) , 594-596. https://doi.org/10.1002/dta.244
    10. Reyhan Yeşilağaç, Perihan Ünak, E. İlker Medine, Çiğdem A. İçhedef, Turkan Ertay, F.Z. Biber Müftüler. Enzymatic synthesis of 125/131I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence. Applied Radiation and Isotopes 2011, 69 (2) , 299-307. https://doi.org/10.1016/j.apradiso.2010.10.027
    11. T. Pallmann, U. Jonas, M. Wagner, M. Thevis, H. Kaeferstein, M.A. Rothschild, K. Bender. Enzyme-assisted synthesis and structural characterization of pure benzodiazepine glucuronide epimers. European Journal of Pharmaceutical Sciences 2010, 39 (4) , 233-240. https://doi.org/10.1016/j.ejps.2009.12.005
    12. Adrian Scaffidi, Robert V. Stick, Vladimír Křen, Pavla Bojarová, Wen‐Ya Lu, Guo‐Qiang Lin, Hui‐Lei Yu, Ai‐Ming Tong, Jian‐He Xu, Cosimo Chiriví, Francesca Sagui, Sergio Riva, Olha Khymenets, Pere Clapés, Teodor Parella, María‐Isabel Covas, Rafael de la Torre, Jesús Joglar, Matthias Kittelmann, Lukas Oberer, Reiner Aichholz, Oreste Ghisalba. Enzymatic Synthesis of Glycosides and Glucuronides. 2009, 227-254. https://doi.org/10.1002/9780470748589.ch7
    13. Anna Alonen, Minna Gartman, Olli Aitio, Moshe Finel, Jari Yli-Kauhaluoma, Risto Kostiainen. Synthesis, structure characterization, and enzyme screening of clenbuterol glucuronides. European Journal of Pharmaceutical Sciences 2009, 37 (5) , 581-587. https://doi.org/10.1016/j.ejps.2009.05.003
    14. Takuji Shoda, Kiyoshi Fukuhara, Yukihiro Goda, Haruhiro Okuda. 4-Hydroxy-3-methoxymethamphetamine Glucuronide as a Phase II Metabolite of 3,4-Methylenedioxymethamphetamine: Enzyme-Assisted Synthesis and Involvement of Human Hepatic Uridine 5'-Diphosphate-Glucuronosyltransferase 2B15 in the Glucuronidation. Chemical and Pharmaceutical Bulletin 2009, 57 (5) , 472-475. https://doi.org/10.1248/cpb.57.472
    15. Anna Alonen, Johanna Jansson, Sirkku Kallonen, Alexandros Kiriazis, Olli Aitio, Moshe Finel, Risto Kostiainen. Enzyme-assisted synthesis and structure characterization of glucuronic acid conjugates of losartan, candesartan, and zolarsartan. Bioorganic Chemistry 2008, 36 (3) , 148-155. https://doi.org/10.1016/j.bioorg.2008.02.004
    16. Laura Hintikka, Tiia Kuuranne, Olli Aitio, Mario Thevis, Wilhelm Schänzer, Risto Kostiainen. Enzyme-assisted synthesis and structure characterization of glucuronide conjugates of eleven anabolic steroid metabolites. Steroids 2008, 73 (3) , 257-265. https://doi.org/10.1016/j.steroids.2007.10.008
    17. Mika Kurkela, Anne-Sisko Patana, Peter I. Mackenzie, Michael H. Court, Christopher G. Tate, Jouni Hirvonen, Adrian Goldman, Moshe Finel. Interactions with other human UDP-glucuronosyltransferases attenuate the consequences of the Y485D mutation on the activity and substrate affinity of UGT1A6. Pharmacogenetics and Genomics 2007, 17 (2) , 115-126. https://doi.org/10.1097/FPC.0b013e328011b598
    18. Olha Khymenets, Jesús Joglar, Pere Clapés, Teodor Parella, María‐Isabel Covas, Rafael de la Torre. Biocatalyzed Synthesis and Structural Characterization of Monoglucuronides of Hydroxytyrosol, Tyrosol, Homovanillic Alcohol, and 3‐(4′‐Hydroxyphenyl)propanol. Advanced Synthesis & Catalysis 2006, 348 (15) , 2155-2162. https://doi.org/10.1002/adsc.200606221
    19. Leena Luukkanen, Jyrki Taskinen, Mika Kurkela, Risto Kostiainen, Jouni Hirvonen, Moshe Finel. KINETIC CHARACTERIZATION OF THE 1A SUBFAMILY OF RECOMBINANT HUMAN UDP-GLUCURONOSYLTRANSFERASES. Drug Metabolism and Disposition 2005, 33 (7) , 1017-1026. https://doi.org/10.1124/dmd.105.004093
    20. Kati S. Hakala, Bohumila Suchanova, Leena Luukkanen, Raimo A. Ketola, Moshe Finel, Risto Kostiainen. Rapid simultaneous determination of metabolic clearance of multiple compounds catalyzed in vitro by recombinant human UDP-glucuronosyltransferases. Analytical Biochemistry 2005, 341 (1) , 105-112. https://doi.org/10.1016/j.ab.2005.03.003
    21. Mika Kurkela, Jouni Hirvonen, Risto Kostiainen, Moshe Finel. The interactions between the N-terminal and C-terminal domains of the human UDP-glucuronosyltransferases are partly isoform-specific, and may involve both monomers. Biochemical Pharmacology 2004, 68 (12) , 2443-2450. https://doi.org/10.1016/j.bcp.2004.08.019
    22. Eivor Elovaara, Jouni Mikkola, Leena Luukkanen, Laurence Antonio, Sylvie Fournel-Gigleux, Brian Burchell, Jacques Magdalou, Jyrki Taskinen. ASSESSMENT OF CATECHOL INDUCTION AND GLUCURONIDATION IN RAT LIVER MICROSOMES. Drug Metabolism and Disposition 2004, 32 (12) , 1426-1433. https://doi.org/10.1124/dmd.104.000992
    23. Päivi Lehtonen, Heli Siren, Ilkka Ojanperä, Risto Kostiainen. Migration behaviour and separation of tramadol metabolites and diastereomeric separation of tramadol glucuronides by capillary electrophoresis. Journal of Chromatography A 2004, 1041 (1-2) , 227-234. https://doi.org/10.1016/j.chroma.2004.04.031
    24. Mika Kurkela, Saila Mörsky, Jouni Hirvonen, Risto Kostiainen, Moshe Finel. An Active and Water-Soluble Truncation Mutant of the Human UDP-Glucuronosyltransferase 1A9. Molecular Pharmacology 2004, 65 (4) , 826-831. https://doi.org/10.1124/mol.65.4.826
    25. Mika Kurkela, J. Arturo Garcı́a-Horsman, Leena Luukkanen, Saila Mörsky, Jyrki Taskinen, Marc Baumann, Risto Kostiainen, Jouni Hirvonen, Moshe Finel. Expression and Characterization of Recombinant Human UDP-glucuronosyltransferases (UGTs). Journal of Biological Chemistry 2003, 278 (6) , 3536-3544. https://doi.org/10.1074/jbc.M206136200
    26. Joshua D Lambert, Dedun Zhao, Ross O Meyers, Robert K Kuester, Barbara N Timmermann, Robert T Dorr. Nordihydroguaiaretic acid: hepatotoxicity and detoxification in the mouse. Toxicon 2002, 40 (12) , 1701-1708. https://doi.org/10.1016/S0041-0101(02)00203-9
    27. Matthew G. Soars, Edward L. Mattiuz, David A. Jackson, Palaniappan Kulanthaivel, William J. Ehlhardt, Steven A. Wrighton. Biosynthesis of drug glucuronides for use as authentic standards. Journal of Pharmacological and Toxicological Methods 2002, 47 (3) , 161-168. https://doi.org/10.1016/S1056-8719(02)00231-9
    28. Laurence Antonio, Joël-Paul Grillasca, Jyrki Taskinen, Eivor Elovaara, Brian Burchell, Marie-Helene Piet, Brian Ethell, Mohamed Ouzzine, Sylvie Fournel-Gigleux, Jacques Magdalou. Characterization of Catechol Glucuronidation in Rat Liver. Drug Metabolism and Disposition 2002, 30 (2) , 199-207. https://doi.org/10.1124/dmd.30.2.199
    29. Helena Keski-Hynnilä, Knut Raanaa, Markus Forsberg, Pekka Männistö, Jyrki Taskinen, Risto Kostiainen. Quantitation of entacapone glucuronide in rat plasma by on-line coupled restricted access media column and liquid chromatography–tandem mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 2001, 759 (2) , 227-236. https://doi.org/10.1016/S0378-4347(01)00226-2
    30. Helena Keski-Hynnilä, Knut Raanaa, Jyrki Taskinen, Risto Kostiainen. Direct analysis of nitrocatechol-type glucuronides in urine by capillary electrophoresis–electrospray ionisation mass spectrometry and tandem mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 2000, 749 (2) , 253-263. https://doi.org/10.1016/S0378-4347(00)00413-8
    31. Päivi Lehtonen, Sanna Lehtinen, Liisa Mälkki-Laine, Tom Wikberg. Micellar electrokinetic capillary chromatography method for direct determination of glucuronides of entacapone and its (Z)-isomer in human urine. Journal of Chromatography A 1999, 836 (1) , 173-188. https://doi.org/10.1016/S0021-9673(99)00082-5
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect