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• 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.

Synthetic Challenges posed by Cyanthiwigin F• 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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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• 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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