Asymmetric Total Synthesis of Vindoline Daisuke Kato Yoshikazu

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

3 D model of Vindoline 1

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 2

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. • Vinblastine is 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. 3

Retrosynthesis 4

Retrosynthesis - 2 5

Forward Synthesis 6

Forward Synthesis - 2 7

Key Cycloaddition Cascade 8

Key Cycloaddition Cascade - 2 9

Forward Synthesis - 3 10

Forward Synthesis - 4 11

Some Details 12

Some Details - 2 13

Thank you for listening 14