Cyanthiwigin

The total synthesis of (-)-cyanthiwigin F by
means of double catalytic enantioselective
alkylation
J.A. Enquist, Jr., B.M. Stoltz, Nature 2008,453,1228
Presented by Vijayarajan Devannah on 5/7/2013
About Professor Brain M. Stoltz
Education and Professional Experience
• B.S., Indiana University of Pennsylvania 1993
• Ph.D., Yale University (John Wood) 1997
• NIH posdoctoral Fellow, Harvard University ( E. J. Corey ) 1998-2000
• Currently professor of chemistry at California Institute of Technology, Pasadena.
Honors and Awards
• Camille and Henry Dreyfus New Faculty Award, 2000
• Glaxosmithkline Chemistry scholar Award 2002 and 2003
• Amgen Young investigator Award 2003
• Arthur C Cope Scholar Award from the American Chemical Society 2005
• E J Corey Award for outstanding original contribution in the organic synthesis by
a young investigator, 2009
• H.C. Brown Lecturer in Organic Chemistry, Purdue University, Indiana, 2011
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About Cyanthiwigin F
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Isolated from the sea sponge Myrmekioderma styx,
Cyanthiwigin F is one of 30 known cyanthiwigin natural products, which
belongs to a larger class of bioactive molecules known as cyathins.
Cyathins display a wide range of biological properties including antimicrobial
activity, antineoplastic actions, stimulation of nerve growth factor synthesis,
and κ-opioid receptor agonism.
Cyanthiwigin F exhibits cytotoxicity activity against human primary tumour
cells with a half-maximal inhibitory concentration of 3.1μg/ml.
N
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Synthetic
Challenges
posed
by
Cyanthiwigin
FF
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Construction of two all-carbon quaternary stereocentres at the A-B and B-C
ring juncture.
Fused 5-6-7 ring system.
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b
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Retrosynthesis
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Synthesis of diketone through stereoablative and
enantioselective double allylation
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Stereochemical analysis of bis(β-ketoester)
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Synthesis of bicyclic aldehyde through olefin
metathesis
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Final Stages and completion of total synthesis of
cyanthiwigin F
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Conclusion
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They achieved the catalytic enantioselective synthesis of the cyanthin
diterpenoid (-)-cyanthiwigin F in 10 steps.
Total yield is 1.8%
Introduction of two chiral centers in one pot with excellent ee
Tandem ring-closing and cross metathesis
No protection and Deprotection involved.
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Thank You
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