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Synfacts 2011(10): 1039-1039  
DOI: 10.1055/s-0030-1261144
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of (+)-Liphagal

Contributor(s):Steven V. Ley, Sean Newton
J. J. Day, R. M. McFadden, S. C. Virgil, H. Kolding, J. L. Alleva, B. M. Stoltz*
California Institute of Technology, Pasadena, USA
The Catalytic Enantioselective Total Synthesis of (+)-Liphagal
Angew. Chem. Int. Ed.  2011,  50:  6814-6818  
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Publication History

Publication Date:
20 September 2011 (online)

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Key words

enantioselective Tsuji allylation - photocycloaddition - ring expansion - olefin reduction

Significance

(+)-Liphagal was isolated in 2006 from the Caribbean sponge Aka coralliphaga and belongs to a family of phosphatidylinositol 3-kinase (PI3K) inhibitors. Structurally, (+)-liphagal consists of an unprecedented [6-7-5-6] tetracyclic motif. Herein, the first catalytic enantioselective approach is reported.

Comment

This synthesis utilizes an enantioselective Tsuji-type allylation developed within the Stoltz group and a two-step oxidation-cyclization procedure to yield previously reported enone D with good enantioselectivity. Epimerization at C10 followed by cyclization enables hydrogenation of the trisubstituted olefin, yielding the trans-fused ring as the only product.

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