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

摘要

Polymer-supported N-(2-oxo-ethyl)-derivatized Ser/Thr/Cys-containmg dipeptides were synthesized and subjected to acid-mediated tandem N-acylium ion cydiza-tion-nucleophilic addition to yield tetrahydro-2H-oxazolo-[3,2-a]pyrazin-S(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 pephdomimetics. The traceless synthesis of bicycles is also reported as part of this work