1. Kiyoun Lee and Dale L. Boger*
TOTAL SYNTHESES OF (−)-KOPSIFOLINE D AND (−)-DEOXOAPODINE: DIVERGENT TOTAL SYNTHESIS VIA LATE-STAGE KEY STRATEGIC BOND FORMATION
Kiyoun Lee and Dale L. Boger*

2. Introduction
Retrosynthesis of the nature product
Procedure of synthesis
conclusion

3. Introduction -natural product (-)-kopsifoline D – 1
Structure
Property
term
Name
(-)-kopsifoline D
Isolated from
Kopsia fruticosa
Isolated by
Kam and Choo
Biological actitivity
Fused 6/5/5/6/6/5 ring system 6環 :indole structure. heterocyclic ring.4 chiral center.

4. Introduction -natural product (-)-deoxoapodine - 2
Structure
Property
term
Name
(-)-deoxoapodine
Isolated from
Tebernae armeniaca
Isolated by
Biological actitivity
Fused 6/5/5/6/6/5 ring system 6環: indole structure . furan

5. Introduction -relative natural product
這一系列的天然物皆為6環結構，主要差別在於苯環上的取代基、double bond or hydroxyl group 及amine and imine

6. Introduction - the review of the nature product Dale L. Boger synthesis

7. Introduction -Previous reference synthesis of kopsifoline alkaloid framework
Reference: Tetrahedron 63 (2007) 5962–5976

8. Introduction -Previous reference Total Synthesis of (+)-Fendleridine (Aspidoalbidine) and (+)-1-Acetylaspidoalbidine
Reference: J. AM. CHEM. SOC. 9 VOL. 132, NO. 9, 2010

9. Introduction -Previous reference total Synthesis of Kopsinine
Reference:Org. Lett., Vol. 15, No. 4, 2013

10. Introduction
Retrosynthesis of the nature product
Procedure of synthesis
conclusion

11. Retrosynthesis of monoterpen indole alkaloids

12. Introduction
Retrosynthesis of the nature product
Procedure of synthesis
conclusion

13. Procedure of synthesis -Synthesis of the initial material -Synthesis of the amino-1,3,4-oxadiazole (12)
4-Toluenesulfonyl chloride
1,3,4-oxadiazole

14. Procedure of synthesis -Synthesis of the initial material -4-(2-tert-butyldimethylsilyloxy)pent-4-enoic acid (13)

15. Procedure of synthesis -Synthesis of the key intermediate 15
A dipolar cycloaddition

16. Procedure of synthesis -synthesis of (-)-Kopsifoline D
Sodium cyanoborohydride
Carbonylbenzyl
Selenoxide elimination

17. Procedure of synthesis -Total synthesis of (-)-Deoxapodine

18. Introduction
Retrosynthesis of the nature product
Procedure of synthesis
conclusion

19. CONCLUSION
a powerful approach to synthesize the key intermediate and apply on the series of Kopsifolines.
the yield of the (-)-kopsifiline D is 5.7% (13step)
from the two intermediate 15
the yield of the (−)-Deoxoapodine 4.4% (12step)

20. CONCLUSION Publish date author step yield production Albert Padwa 7
Tetrahedron 63 (2007) 5962–5976.
Albert Padwa 7
non
kopsifoline
alkaloid framework
J. AM. CHEM. SOC. 2010, 132, 3009–3012
Dale L. Boger 16
12.2%
(+)-Fendleridine
J. AM. CHEM. SOC. 2010, 132, 3685–3687 22
2.1%
Vindoline
ORGANIC
LETTERS
2013
Vol. 15, No. 4
868–870
17%from the key intermediate
Kopsinine
J. Am. Chem. Soc. 2014,136, 13
5.7%from the two intermediate
(−)-Kopsifoline D 12
4.4% from the two intermesiate
(−)-Deoxoapodine

21. REFERENCE Tetrahedron 63 (2007) 5962–5976 Angew. Chem. Int. Ed. 2006
J. AM. CHEM. SOC. 2006, 128,
J. AM. CHEM. SOC. 2010, 132, 13533–13544
J. Am. Chem. Soc. 2012, 134, 13240−13243
J. AM. CHEM. SOC. 2009, 131, 4904–4916
J. AM. CHEM. SOC. 2010, 132, 3009–3012
J. AM. CHEM. SOC. 2010, 132, 3685–3687
J. AM. CHEM. SOC. 2010, 132, 8489–8495
J. Med. Chem. 2013, 56, 483−495
J. Org. Chem. 2002, 67,
J. Org. Chem., Vol. 63, No. 3, 1998
Org. Lett., Vol. 7, No. 4, 2005

22. THE END

23. PROBLEM
Long strategy.
The concept of the key intermediate is important.