Synfacts 2005(0): 0010-0010  
DOI: 10.1055/s-2005-865347
Synthesis of Natural Products and Drugs
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Zn Aldol Additions: Asymmetric Synthesis of Fostriecin

Contributor(s): Philip Kocienski
B. M. Trost*, M. U. Frederiksen, J. P. N. Papillion, P. E. Harrington, S. Shin, B. T. Shireman
Stanford University, USA
Dinuclear Asymmetric Zn Aldol Additions: Formal Asymmetric Synthesis of Fostriecin
J. Am. Chem. Soc.  2005,  127:  3666-3667  
Further Information

Publication History

Publication Date:
20 July 2005 (online)


Significance

Fostriecin is a metabolite of Streptomyces pulveraceous. It is a potent inhibitor of protein phosphatase 2A and it is cytotoxic towards leukemia and many other cell lines.

Comment

The two markworthy steps in this short synthesis are (a) the large scale (49.6 mmol) direct asymmetric Zn-catalyzed aldol reaction illustrated and (b) a Pd-catalyzed alkenylsilane cross-coupling which installs the conjugated triene moiety. The synthesis was accomplished in 14 steps for the longest linear sequence and gave dephospho-fostriecin in 8.5% overall yield.