Enzyme-assisted synthesis and structural characterization of nitrocatechol glucuronides

Autor: Jyrki Taskinen, Eivor Elovaara, Pekka Ottoila, Ilkka Kilpeläinen, Heli Kangas, Leena Luukkanen
Rok vydání: 1999
Předmět:
Male
Magnetic Resonance Spectroscopy
Spectrophotometry
Infrared
Biomedical Engineering
Glucuronidation
Catechols
Pharmaceutical Science
Bioengineering
Glucuronates
In Vitro Techniques
Spectrometry
Mass
Fast Atom Bombardment
030226 pharmacology & pharmacy
High-performance liquid chromatography
Catalysis
Nitrophenols
03 medical and health sciences
chemistry.chemical_compound
Benzophenones
0302 clinical medicine
Column chromatography
Pentanones
Nitriles
medicine
Animals
Enzyme Inhibitors
Rats
Wistar
Chromatography
High Pressure Liquid
030304 developmental biology
Pharmacology
0303 health sciences
Chromatography
Tolcapone
Chemistry
Organic Chemistry
Extraction (chemistry)
Catechol O-Methyltransferase Inhibitors
Stereoisomerism
Nitecapone
Rats
Microsomes
Liver
Stereoselectivity
Spectrophotometry
Ultraviolet
Biotechnology
medicine.drug
Zdroj: Bioconjugate chemistry. 10(1)
ISSN: 1043-1802
Popis: Enzyme-assisted synthesis and characterization are described for 3-O-beta-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-beta-D- and 2-O-beta-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.
Databáze: OpenAIRE
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