Studies on the reactions between daptomycin and glyceraldehyde.
The objectives of this project were to determine the reaction pathways of daptomycin in the presence of glyceraldehyde in acidic solutions, and to quantitate the kinetics of the major pathways. In the presence of glyceraldehyde (pH range 1-7 at 25 to 60 degrees C), daptomycin formed two major products separable by RP-HPLC. The products were identified using UV spectroscopy, fluorimetry, mass spectrometry, and 2D-1H NMR. The reaction scheme involved the reversible formation of imine and anilide derivatives. Carbinolamine was believed to be a common intermediate in formation pathways of both products. The carbinolamine intermediate underwent either acid catalyzed dehydration resulting in imine formation or intramolecular hydrogen bonding and bond cleavage giving rise to anilide formation. In mild acid conditions, both products reversed to daptomycin. The reaction between daptomycin and glyceraldehyde was first-order with respect to both reactants. In a pH range of 1-7, the imine formation rate was pH dependent with a maximum rate at approximate pH values of 3-4. The observed pH dependence was consistent with the pH dependence of typical amine-aldehyde reactions.
Muangsiri
Walaisiri
W
Division of Pharmaceutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA. walaisiri@yahoo.com
Kearney
William R
WR
Teesch
Lynn M
LM
Kirsch
Lee E
LE
D000813:Anilides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017576:Daptomycin / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005985:Glyceraldehyde / Q000032:analysis / Q000737:chemistry* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods; D008968:Molecular Conformation; D013050:Spectrometry, Fluorescence / Q000379:methods; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D000813:Anilides; D005985:Glyceraldehyde; D017576:Daptomycin