Synthesis of Stereochemically Defined Ψ Pseudopeptides

Article abstract of DOI:10.1021/jo00284a032

A general synthesis of Ψ pseudopeptides 3, with defined stereochemistry at the new asymmetric center, is described.Grignard reaction of amino acid derived oxazolidines 10 and 11 gave separable mixtures of benzyl-proteted diamino alcohols 12-15, the stereochemistry of which could be defined by conversion to imidazolidones 16-19.Studies on the oxidation of these alcohols yielded a procedure for the conversion of aldehydes to acyl cyanides which is compatible with sensitive functionality.Application of this methodology to a series of monoprotected diamino alcohols (e.g. 39) gave rise to pseudotripeptides (e.g. 41) upon in situ coupling with (S)-phenylalanine methyl ester hydrochloride.This synthesis allows for variations in R¹ and R² of pseudopeptide 3 and permits the introduction of bulky appendages along the peptide backbone.