Polymer-Supported Stereoselective Synthesis of Tetrahydro-2<i>H</i>-oxazolo[3,2-<i>a</i>]pyrazin-5(3<i>H</i>)-ones from <i>N</i>-(2-Oxo-ethyl)-Derivatized Dipeptides via Eastbound Iminiums

Abstract

Polymer-supported N-(2-oxo-ethyl)-derivatized Ser/Thr/Cys-containing dipeptides were synthesized and subjected to acid-mediated tandem N-acylium ion cyclization–nucleophilic addition to yield tetrahydro-2H-oxazolo[3,2-a]pyrazin-5(3H)-ones. The reaction conditions and building-block combinations for stereoselective synthesis of the newly formed asymmetric carbon were developed. The synthesis was fully compatible with solid-phase peptide synthesis, and the products serve as conformationally constrained peptidomimetics. The traceless synthesis of bicycles is also reported as part of this work.