New Applications of PhI(OAc)(2) in Synthesis: Total Synthesis and SAR Development of Potent Antitumor Natural Product Psymberin/Irciniastatin A

A novel PhI(OAc)(2)-mediated oxidative cyclization reaction is discovered for the synthesis of alpha-oxy N-acyl aminals and hemiaminals in good yields from readily synthesized N-acyl enamines. This methodology represents a cascade process to construct the core structure of the pederin family of natural products. The total synthesis of psymberin, a member of the pederin family, is accomplished using this ring-closure reaction as the key step. This new method is further showcased in the preparation of advanced psymberin analogues. The biological data of these analogues are presented. 1 Introduction 2 Methodology Development 3 Total Synthesis of Psymberin 4 Synthesis of Psymberin Analogues: The Discovery of C11-Deoxypsymberin 5 Conclusion