Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2011
- Accession Number
- ADA571132
Entities
People
- Anders Wallqvist
- Christopher A. Leclair
- Daniele Padula
- David J. Maloney
- Gennaro Pescitelli
- Ilja Khavrutskii
- Janet Skerry
- John H. Cardellina Ii
- Leonard A. Smith
- Rebecca C. Vieira
- Vanessa Eccard
- Vicki Montgomery
- Virginia Roxas-duncan
- William Leister
- Xin Hu
- Yvette Campbell
Organizations
- United States Army Medical Research Institute of Infectious Diseases