•A series of novel N-methylated and N,N′-dimethylated 2,5-DKPs were prepared.•Conformational analysis of N-methylated and N,N′-dimethylated 2,5-DKPs based on 1H NMR spectroscopy were performed.•Single crystal X-ray structural analysis of N1-methylated and N4-methylated 2,5-DKPs was performed.•N4-methylation of mono-benzylated 2,5-DKPs was found to change their conformation from folded to extended.N4-methylation of (3S,6S)-3-alkyl-6-benzylpiperazine-2,5-diones (S,S)-1a–c was found to change their folded conformation to an extended conformation. Conformational aspects of N1- and/or N4-methylated (S,S)-1a–c were revealed by single crystal X-ray crystallography and 1H NMR spectroscopy.

A novel synthetic approach to glycerophospholipids featuring the use of Horner–Wadsworth–Emmons reagents as masked glycerophospholipids has been developed. Based on this method, phosphatidic acid (PA), phosphatidylethanolamine (PE), and phosphatidylcholine (PC) containing palmitoyl moieties were readily synthesized from a mixed phosphonoacetate as a common key intermediate.

The Horner–Wadsworth–Emmons reactions of ethyl 2-fluoro-2-diethylphosphonoacetate with 2-(4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl)cyclopentanone (2-OBO-cyclopentanone) using n-butyllithium furnished the corresponding tetra-substituted fluoroolefin in an E-selective manner (E:Z = 95:5). A facile synthesis of rac-N-Cbz-Gly-Ψ[(E)-CFC]-Pro-OH as a dipeptide isostere was achieved based on the E-selective Horner–Wadsworth–Emmons reaction.