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 Xaapsi[CH2O]Ala/Gly pseudodipeptides in good yields and excellent diastereoselectivity from azido alcohols and (R)-2-chloropropionic acid or tort-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. (C) 2002 Elsevier Science Ltd. All rights reserved.