Privilege Structures: New Strategies for the Synthesis of Cyclic Tetrapeptides

Abstract

The term privilege structure has been coined [1] to describe classes of molecules that are capable of binding to multiple, unrelated receptors. For example, various cyclic tetrapeptides have been isolated from bioactive fractionation and have wide-ranging biological activities, including anti-cancer, anti-parasitic, opiate agonist, tyrosinase inhibitors and potential selective herbicides. No synthetic routes have been described that enable access to this “difficult” class of compounds in a versatile fashion. In this work, we have developed a strategy that makes use of two types of auxiliaries, one that enables a ring closure/ring contraction process, and a second one which performs the role of promoting cis-amide bond conformations at selected positions in the backbone.