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 t...

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Bibliographic Details
Published in:Journal of organic chemistry 2001-06, Vol.66 (11), p.3747-3752
Main Authors: Edmonds, Michael K, Abell, Andrew D
Format: Article
Language:English
Subjects:
Anti-HIV Agents - chemical synthesis
Anti-HIV Agents - chemistry
HIV Protease Inhibitors - chemical synthesis
HIV Protease Inhibitors - chemistry
Indicators and Reagents
Magnetic Resonance Spectroscopy
Molecular Conformation
Nelfinavir - chemical synthesis
Saquinavir - chemical synthesis
Spectrometry, Mass, Electrospray Ionization
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Summary: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 ). A potential application of this isostere in the synthesis of HIV protease inhibitors is also discussed.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo0016834