Enzyme-assisted synthesis and structural characterization of nitrocatechol glucuronides

Bioconjug Chem. Jan-Feb 1999;10(1):150-4. doi: 10.1021/bc980064n.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzophenones / chemical synthesis*
  • Benzophenones / chemistry
  • Catechol O-Methyltransferase Inhibitors*
  • Catechols / chemical synthesis*
  • Catechols / chemistry
  • Chromatography, High Pressure Liquid
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Glucuronates / chemical synthesis*
  • Glucuronates / chemistry
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Male
  • Microsomes, Liver / enzymology
  • Nitriles
  • Nitrophenols
  • Pentanones / chemical synthesis*
  • Pentanones / chemistry
  • Rats
  • Rats, Wistar
  • Spectrometry, Mass, Fast Atom Bombardment
  • Spectrophotometry, Infrared
  • Spectrophotometry, Ultraviolet
  • Stereoisomerism
  • Tolcapone

Substances

  • Benzophenones
  • Catechol O-Methyltransferase Inhibitors
  • Catechols
  • Enzyme Inhibitors
  • Glucuronates
  • Nitriles
  • Nitrophenols
  • Pentanones
  • entacapone
  • nitecapone
  • Tolcapone