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 chiralphosphonate 7 under base-sensitive conditions to give a chiral enone (2R)-24a which was reducedto afford the desired trans alkene isosteres (2R,5R)-6a and (2R,5S)-6b (Scheme ). A potentialapplication of this isostere in the synthesis of HIV protease inhibitors is also discussed.