Solid-Phase Synthesis of Bicyclic Dipeptide Mimetics by Intramolecular Cyclization of Alcohols, Thiols, Amines, and Amides with N-Acyliminium Intermediates

A general strategy for the solid-phase synthesis of structurally diverse bicyclic dipeptide mimetics is presented. Depending on the amino acid side-chain (R(1)), peptide-derived N-acyliminium intermediates may undergo nucleophilic attack from either side-chain functional groups (-OH, -NH(2), -SH, and -CONH(2)) or the amide backbone (-CONH-) of the peptide, thus affording a range of aza-, thia-, and oxabicycloalkanes in excellent purity and diastereoselectivity. [reaction: see text]