Total Synthesis of Halichondrin A
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Total Synthesis of Halichondrin A Atsushi Ueda, Akihiko Yamamoto, Daisuke Kato and Yoshito Kishi Current literature Andrey Kuzovlev 18.09.2014 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA J. Am. Chem. Soc., 2014, 136, 5171–5176 DOI: 10.1021/ja5013307 Halichondria okadai
Transcript of Total Synthesis of Halichondrin A
Total Synthesis of Halichondrin A
Atsushi Ueda, Akihiko Yamamoto, Daisuke Kato and Yoshito Kishi
Current literature
Andrey Kuzovlev
18.09.2014
Department of Chemistry and Chemical Biology,
Harvard University, Cambridge, Massachusetts, USA
J. Am. Chem. Soc., 2014, 136, 5171–5176
DOI: 10.1021/ja5013307
Halichondria okadai
Halicondrins are polyether macrolides.
Isolated from marine sponge
Halichondria okadai by Uemura,
Hirata and co-workers in 1985.
Subgrouped into halichondrins A-C
and norhalichondrin, halichondrin,
homohalichondrin.
Extraordinary in vitro and in vivo
antitumor activity.
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Introduction
Retrosynthetic Analysis of Halichondrin A
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5
6
7
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Synthesis of Precursor for Building Block 6
21 22 23
24 25 26 27
28 29
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Synthesis of Building Block 6
29 30 31
31 32 (6)
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Synthesis of Precursors for Aldehyde 7
33 34 35
36 37 38
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40 41 42
43 44 45
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Synthesis of Aldehyde 7
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35
46 47
47 48 (7)
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Synthesis of Building Block 5
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53 54
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56 (5)
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Synthesis of Building Block 19 (6+7)
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Synthesis of building block 19
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Completion of the Total Synthesis (5+19)
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Completion of the Total Synthesis
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[5,5]-Spiroketal Equilibration
Total synthesis of halichondrin A, included followed key-steps:
Catalytic asymmetric Ni/Cr-mediated coupling
Shiina macrolactonization
Dess-Martin oxidation
Newly discovered highly selective TMSOTf-mediated
equlibration
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Conclusions
Thank you for your attention!
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Ni/Cr coupling
