1. Total Synthesis of (±)-Cylindricine C
Guillaume Lapointe, Kurt Schenk, and Philippe Renaud＊
Org. Lett., 2011, 13,
reporter: Hui-ting Chang

2. OUTLINE Stuctures of family Isolation and bioactivity Past synthesis
Retrosynthetic analysis
Synthesis
Conclusion
Summary

3. Structures of family

4. Isolation and bioactivity
Isolated from the marine ascidian Clavelina cylindrica.
Bioactivity ：
against brine shrimp larvae in bioassay.

5. STRATEGIES FOR FORMING KEY PYRROLO-QUINOLINE RING
Intramolecular Michael addition
Iminium ion/diene cyclization
Oxidative spirocyclization
Aza〔3+3〕annulation
Mannich reaction

6. PAST SYNTHESIS Total synthesis of (-)-Cylindricine C
J. Org. Chem. 1999, 64,
Strategies

7. PAST SYNTHESIS
An N-Acyliminium Cyclization Approach to a Total Synthesis of (+)-Cylindricine C
J. Org. Chem. 2005, 70,
Strategies

8. PAST SYNTHESIS
Fully Stereocontrolled Total Syntheses of (-)- Cylindricine C
Angew. Chem. Int. Ed. 2004, 43,
Strategies

9. PAST SYNTHESIS
A Concise Total synthesis of (-)- Cylindricine C through a Stereoselective Intramolecular Aza- 〔3+3〕 Annulation Strategy
Org. Lett. 2006, 8,
Vinyl amide + vinyl iminium = aza-〔3+3〕 annulation
Strategies

10. PAST SYNTHESIS
Short Synthesis of (+)-Cylindricine C by Using a Catalytic Asymmetric Michael Reaction with a Two-Center Organocatalyst
Angew. Chem. Int. Ed. 2006, 45, 4635 –4637
Two-center organocatalyst:
TaDiAS, tartrate-derived diammonium salt that efficiently catalyzes
phase-transfer alkylation

11. RETROSYNTHETIC ANALYSIS

12. Preparation of the key substrate for the carboazidation step

13. PREPARATION OF THE KEY SUBSTRATE OF COMPOUND 4 FOR THE CARBOAZIDATION STEP

14. Preparation of trans-azide
Method A: (Bu3Sn)2 (1.2 equiv.), t-BuON (0.1 equiv.), 75％, (trans/cis=7:3)
Method B: Et3B (4.0 equiv.), air, rt, 59 ％, (trans/cis=7:3)

15. Synthesis of the stereochemical tricyclic amine

16. SYNTHESIS OF 13-EPI-CYLINDRICINE C

17. Total synthesis of (±)-cylindricine C

18. CONCLUSION Ring formation ： A → key azaspirocenter → B and C.
The concise syntheses of 13-epi-cylindricineC and cylindricine C were achieved from 1-octyne in 15% and 11% yields, respectively.
The strategy involves the preparation of the tricyclic skeleton via a radical α-iodoketone carboazidation/bis-reductive amination sequence.

19. SUMMARY Target molecule Journal Key step Steps Yield
(±)-Cylindricine C
Org. Lett. 2011, 13,
Carbonazidation
Bis-reductive amination 17
11％
(-)- Cylindricine C
J. Org. Chem. 1999, 64, 5183–5187.
Intramolecular Michael addition 11
12％
(+)- Cylindricine C
J. Org. Chem. 2005, 70,
Iminium ion/diene cyclization 8
11.1％
Angew. Chem., Int. Ed. 2006, 43, 4336 –4338
Oxidative spirocyclizaation 21
14.5％
Org. Lett. 2006, 8,
Aza〔3+3〕annulation 22
4.5％
(+)-Cylindricine C
Angew. Chem., Int. Ed. 2006, 45, 4635 –4637
Michael addition
Mannich reaction 6
17.6％

20. Thanks for
your attention