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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.

SUBMITTER: Cardellina JH

PROVIDER: S-EPMC3217201 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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

Cardellina John H JH Vieira Rebecca C RC Eccard Vanessa V Skerry Janet J Montgomery Vicki V Campbell Yvette Y Roxas-Duncan Virginia V Leister William W Leclair Christopher A CA Maloney David J DJ Padula Daniele D Pescitelli Gennaro G Khavrutskii Ilja I Hu Xin X Wallqvist Anders A Smith Leonard A LA

ACS medicinal chemistry letters 20110301 5

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 bi ...[more]

PMID: 22102940

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