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Synthesis 2009(17): 2855-2872  
DOI: 10.1055/s-0029-1216926
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Ning Shao*, Xianhai Huang*, Anandan Palani, Robert Aslanian, Alexei Buevich, John Piwinski, Robert Huryk, Cynthia Seidel-Dugan
Department of Chemical Research, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA
Fax: +1(908)7407664; e-Mail: xianhai.huang@spcorp.com; e-Mail: ning.shao@spcorp.com;
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Publication History

Received 30 May 2009
Publication Date:
07 August 2009 (online)

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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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