Asymmetric Total Synthesis of Vindoline

1. Asymmetric Total Synthesis of Vindoline Daisuke Kato, Yoshikazu Sasaki, and Dale L. Boger* Lan Wang Chem 635 February 19 2013

2. 3D model of Vindoline

3. Dale L. Boger, Ph.D. • B.S. University of Kansas, 1975 • Ph.D. Harvard University, 1980 • Assistant/Associate Professor of Medicinal Chemistry, University of Kansas, 1979-85 • Associate Professor/Professor of Chemistry, Purdue University, 1985-91 • Professor, The Scripps Research Institute, 1991-present • His research is focused in synthetic methodology and natural products total synthesis • > 520 publications

4. History of Vindoline/Vinblastine • Vindoline, a major alkaloid of Cantharanthus roseus, constitutes the more complex lower half of vinblastine and serves as both a biosynthetic and synthetic precursor to this important natural product. • Vinblastineis an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, and et al. It was traditionally obtained from Catharanthus roseus, also known as Vinca rosea. • Vinblastine was first isolated by Robert Noble and Charles Thomas Beer at the University of Western Ontario from the Madagascar periwinkle plant in 1958.

5. Retrosynthesis

6. Retrosynthesis - 2

7. Forward Synthesis

8. Forward Synthesis - 2

9. Key Cycloaddition Cascade

10. Key Cycloaddition Cascade - 2

11. Forward Synthesis - 3

12. Forward Synthesis - 4

13. Some Details

14. Some Details - 2

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