Asymmetric Total Synthesis of (+)-Minfiensine by an Asymmetric Cascade Cyclization Strategy

Abstract

The Strychnos alkaloid minfiensine and a series of akuammiline alkaloids, such as vincorine, aspidophylline A, and picrinine, possess a common core skeleton, a 4a,9a-heterocycle-fused tetrahydrocarbazole. Efficient construction of this core structure in a highly enantioselective manner would facilitate the total synthesis of these alkaloids. In this article, we briefly summarize the established strategies for obtaining this core structure, together with the corresponding total-synthesis routes, and we describe our own effort on the development of a new strategy, the asymmetric cascade dearomative cyclization, for the efficient total synthesis of (+)-minfiensine.

Key words

alkaloids - indoles - minfiensine - asymmetric cascade cyclization - asymmetric allylic alkylation - palladium catalysis

• References

• 1 Massiot G. Thépenier P. Jacquier M.-J. Le Men-Olivier L. Delaude C. Heterocycles 1989; 29: 1435
• 2a Saraswathi V. Mathuram V. Subramanian S. Govindasamy S. Cancer Biochem. Biophys. 1999; 17: 79
• 2b Ramírez A. Garcia-Rubío S. Curr. Med. Chem. 2003; 10: 1891
• 2c Adams GL. Smith AB. III. In The Alkaloids: Chemistry and Biology . Vol. 76, Chap. 3. Knölker HJ. Elsevier/Academic Press; Amsterdam: 2016: 171
• 3a Zu L. Boal BW. Garg NK. J. Am. Chem. Soc. 2011; 133: 8877
• 3b Moreno J. Picazo E. Morrill L. A. Smith J. M. Garg NK. J. Am. Chem. Soc. 2016; 138: 1162
• 4a Smith JM. Moreno J. Boal BW. Garg NK. J. Am. Chem. Soc. 2014; 136: 4504
• 4b Smith JM. Moreno J. Boal BW. Garg NK. J. Org. Chem. 2015; 80: 8954
• 5 Ren W. Wang Q. Zhu J. Angew. Chem. Int. Ed. 2014; 53: 1818
• 6a Dounay AB. Overman LE. Wrobleski AD. J. Am. Chem. Soc. 2005; 127: 10186
• 6b Dounay AB. Humphreys PG. Overman LE. Wrobleski AD. J. Am. Chem. Soc. 2008; 130: 5368
• 7 Jones SB. Simmons B. MacMillan DW. C. J. Am. Chem. Soc. 2009; 131: 13606
• 8 Horning BD. MacMillan DW. C. J. Am. Chem. Soc. 2013; 135: 6442
• 9 Zhang M. Huang X. Shen L. Qin Y. J. Am. Chem. Soc. 2009; 131: 6013
• 10 Zi W. Xie W. Ma D. J. Am. Chem. Soc. 2012; 134: 9126
• 11 Liu Y. Xu W. Wang X. Org. Lett. 2010; 12: 1448
• 12 Liu P. Wang J. Zhang J. Qiu FG. Org. Lett. 2011; 13: 6426
• 13 Ji W. Yao L. Liao X. Org. Lett. 2016; 18: 628
• 14 Li G. Padwa A. Org. Lett. 2011; 13: 3767
• 15 Yu Y. Li G. Jiang L. Zu L. Angew. Chem. Int. Ed. 2015; 54: 12627
• 16 Zhang X. Liu W.-B. Tu H.-F. You S.-L. Chem. Sci. 2015; 6: 4525
• 17 Zhang Z.-X. Chen S.-C. Jiao L. Angew. Chem. Int. Ed. 2016; 55: 8090
• 18 For the construction of the same core structure by Ir(I)-catalyzed asymmetric cascade cyclization in the total synthesis of aspidophylline A, see: Jiang S.-Z. Zeng X.-Y. Liang X. Lei T. Wei K. Yang Y.-R. Angew. Chem. Int. Ed. 2016; 55: 4044