Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A.

نویسندگان

  • John H Cardellina
  • Rebecca C Vieira
  • Vanessa Eccard
  • Janet Skerry
  • Vicki Montgomery
  • Yvette Campbell
  • Virginia Roxas-Duncan
  • William Leister
  • Christopher A Leclair
  • David J Maloney
  • Daniele Padula
  • Gennaro Pescitelli
  • Ilja Khavrutskii
  • Xin Hu
  • Anders Wallqvist
  • Leonard A Smith
چکیده

The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinum neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and (-)-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers.

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عنوان ژورنال:
  • ACS medicinal chemistry letters

دوره 2 5  شماره 

صفحات  -

تاریخ انتشار 2011