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

Abstract

A novel PhI(OAc)₂-mediated oxidative cyclization reaction is discovered for the synthesis of α-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

Key words

(diacetoxyiodo)benzene - psymberin - oxidative cycli­zation - total synthesis - antitumor

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