Total Synthesis of Maoecrystal VReporter: Wang Zhen
Supervisor: Prof. Motomu Kanai
Yoichiro Kuninobu, Ph.D.
2013.09.28
1BackgroundIsolation of maoecrystal V
Structural features and biological activity ofmaoecrystal V

Synthetic studies
Nicolaou′s model studies toward maoecrystal V
Baran′s model studies toward maoecrystal V
Several other total synthesis of maoecrystal V

Conclusion
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Brief introduction of prof. Sun Han–Dong(孙汉董)1958–1962 B.S., Yunnan university
1980 –1982 Tokushima University(德岛大学,研修)1988 Ph.D., Kyoto University, Japan(京都大学)
1983–1989 Kunming Institute of Botany, associate professor
1989 Kunming Institute of Botany, professor
2003 Academician of Chinese Academy of Sciences
Research field: phytochemistry and natural pharmaceutical chemistry
http://sourcedb.kib.cas.cn/zw/zjrc/yszj/200908/t20090810_2361706.html

3Background–Isodon eriocalyx(疏花毛萼香茶菜)

Perennial herb or shrubWidely distributed in southwestern China
Used as a folk medicine for the treatment of sore throat, influenza, infla–mmation, hypertension, and dermatophytosis

Rich in ent–kauranoids with different oxygenation and cleavage patterns,
so far ca. 50 compound isolated, including over 30 new ones identified
Sun, H. D. et al. Org. Lett. 2004, 6, 4327.

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Structure features of maoecrystal V=Compound 1

C19 diterpenoid; An unprecedented and highly congested pentacyclic frameworkSix stereocenters, three of which are vicinal quaternary centers; [2.2.2]Bicyclooct-anone moitey
Isolated in 1994, Confirmed by X–ray crystallography in 2004.
Display potent and selective inhibitory activity against HeLa cell
(IC50 =60 nM)
Sun, H. D. et al. Org. Lett. 2004, 6, 4327.

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Nicolaou′s model studies toward maoecrystal V

K. C. Nicolaou, D. Y.–K. Chen, Chem. Comm. 2010, 46, 70– 72.

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Nicolaou′s model studies toward maoecrystal V

K. C. Nicolaou, D. Y.–K. Chen, Chem. Comm. 2010, 46, 70– 72

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Nicolaou′s model studies toward maoecrystal V

8Y.–K. Chen, et al. , Chem. Eur. J. 2011, 17, 5778.

Nicolaou′s model studies toward maoecrystal V

Y.–K. Chen, et al. , Chem. Eur. J. 2011, 17, 5778.

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Nicolaou′s model studies toward maoecrystal VY.–K. Chen, et al. , Chem. Eur. J. 2011, 17, 5778.

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Baran′s model studies of maoecrystal V
Retrosynthetic of Maoecrystal V

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P. J. Krawczuk, N. Schone, P. S. Baran, Org. Lett. 2009, 11, 4774 –4776

Baran′s model studies of maoecrystal V

P. J. Krawczuk, N. Schone, P. S. Baran, Org. Lett. 2009, 11, 4774 –4776

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Baran′s model studies of maoecrystal V

P. J. Krawczuk, N. Schone, P. S. Baran, Org. Lett. 2009, 11, 4774 –4776

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Trauner′s model studies of maoecrystal VI. Baitinger, P. Mayer, D. Trauner, Org. Lett. 2010, 12, 5656 – 5659.

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First Total Synthesis of Maocrystal V
Introduction of Prof. YangEDUCATION
1989–1992, Ph. D.,The Chinese University of Hong
Kong, advisor: prof. Henry N.C. WONG.
1978–1986, B.S., and M.S., Shenyang College ofPharmacy
Professional experience
2001–present, Professor, Peking University
1998–2001, Institute fellow, Harvard University
1995–1998, Assistant Professor,The Scripps Research Institute1992–1995, Postdoctoral Fellow ,The Scripps Research Institute(total syntheses ofTaxol, brevetoxin A, epothilone A and zaragozic acid). advisor: prof. K.C. Nicolaou.
Research Interest:Total Synthesis of Natural Products, organometallic chemistry, diversity orientedsynthesis, and chemical biology.
http://www.chem.pku.edu.cn/page/zyang/YANG.html 15

Yang′s retrosynthetic analysis of maoecrystal VJ. Gong, G. Lin, C. C. Li, Z. Yang, Org. Lett. 2009, 11, 4770–4773.

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Yang′s total synthesis of maoecrystal V

17J. Gong, G. Lin, C. C. Li, Z. Yang, Org. Lett. 2009, 11, 4770–4773.

Yang′s total synthesis of maoecrystal VJ. Gong, G. Lin, W. Sun, C.-C. Li, Z. Yang, J. Am. Chem. Soc. 2010, 132, 16745 .

18Yang′s total synthesis of maoecrystal V=J. Gong, G. Lin, W. Sun, C.-C. Li, Z. Yang, J. Am. Chem. Soc. 2010, 132, 16745 .

19http://www.nature.com/nature/journal/v468/n7326/full/468871f.html;
http://totallysynthetic.com/blog/?s=maoecrystal+V&x=0&y=0;
http://www.rsc.org/chemistryworld/Issues/2010/December/ColumnTotallySynthetic.asp.

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Second Total Synthesis of Maocrystal V by Prof. Dannishefsky

F. Peng, M. L. Yu, S. J. Danishefsky, Tetrahedron Lett. 2009, 50, 6586;
F. Peng, S. J. Danishefsky. J. Am. Chem. Soc. 2012, 134, 18860.

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Third Total Synthesis of Maocrystal V by A. Zakarian

Zhenhua Gu , A.Zakarian,Org. Lett. 2010, 12, 5656 – 5659;
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Ping Lu, Zhenhua Gu, A. Zakarian.J. Am. Chem. Soc.dx.doi.org/10.1021/ja408231t ..

Conclusion
Nicolaou, Baran, Danishefsky, Zakarian , and Thomson all employedintramolecular Diel–Alder Strategy(IMDA) to construct[2, 2, 2] bicyclicring system.
Trauner proposed a conceptual different strategy to construct the bic–yclic ring system, which proved to be fruiteless in his pratice.
Yang utilized Rh–catalyzed O–H bond insertion to furnish a fully fun–ctioned precusor for IMDA, which smothly solved both THF and lacton–e probloms in one pot.
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Thanks for your attention!

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