Stereoselective Synthesis of Ψ[CH2O] Pseudodipeptides and Conformational Analysis of a PheΨ[CH2O]Ala Containing Analogue of the Drug Desmopressin

A method for synthesis of XaaΨ[CH2O]Ala/Gly pseudodipeptides in good yields and excellent diastereoselectivity from azido alcohols and (R)-2-chloropropionic acid or tert-butyl bromoacetate has been developed. Insertion of one of the pseudodipeptide building blocks in the peptide drug desmopressin revealed that methylene ether isosteres may have only a minor influence on the secondary structure of peptides.