Design and synthesis of a conformationally restricted trans peptide isostere based on the bioactive conformations of saquinavir and nelfinavir.
The design and synthesis of a new peptide isostere which contains a trans alkene core is described. The key step involves a Wadsworth-Emmons reaction between chiral aldehyde (2S)-9a and chiral phosphonate 7 under base-sensitive conditions to give a chiral enone (2R)-24a which was reduced to afford the desired trans alkene isosteres (2R,5R)-6a and (2R,5S)-6b (Scheme 6). A potential application of this isostere in the synthesis of HIV protease inhibitors is also discussed.
Edmonds
M K
MK
Department of Chemistry, University of Canterbury, Private Bag 4800, Christchurch, New Zealand. edmondsm@cpit.ac.nz
Abell
A D
AD
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D019888:Nelfinavir / Q000138:chemical synthesis*; D019258:Saquinavir / Q000138:chemical synthesis*; D021241:Spectrometry, Mass, Electrospray Ionization
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents; D019888:Nelfinavir; D019258:Saquinavir