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DOI: 10.1055/s-0042-1751498
Total Synthesis of Mavacuran Alkaloids via Bioinspired and Non-Bioinspired Strategies
Financial support for this work was provided by the Agence Nationale de la Recherche (ANR) (ANR-15-CE29-0001, ‘Mount Indole’), the Ministère de l’Enseignement Supérieur et de la Recherche (MESRI) (ED 2MIB, Université Paris-Saclay), the Fondation pour le développement de la chimie des substances naturelles et ses applications; sous l’égide de l’Académie des Sciences, Université Paris-Saclay and the Centre National de la Recherche Scientifique (CNRS).
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Abstract
In this account, we report our endeavors towards the total synthesis of the mavacuran alkaloids and some of their highly natural complex bis-indoles. Our studies started with the hemisynthesis of voacalgine A and bipleiophylline, made an excursion to a related family of monoterpene indole alkaloids (total synthesis of 17-nor-excelsinidine) and ended with the total syntheses of several mavacuran alkaloids (16-epi-pleiocarpamine, 16-hydroxymethylpleiocarpamine, taberdivarine H, normavacurine, C-mavacurine, C-profluorocurine, and C-fluorocurine) via a combination of bioinspired and non-bioinspired synthetic routes.
1 Introduction
2 Bioinspired Hemisynthesis of Voacalgine A and Bipleiophylline
3 Total Synthesis of the Mavacuran Alkaloids
4 Bioinspired Oxidative Cyclization of a Geissoschizine Ammonium Derivative to Form the N1–C16 Bond and the E Ring
5 Non-Bioinspired Michael Addition to Form the C15–C20 Bond and the E Ring
6 Conclusion
7 Epilogue
Key words
monoterpene indole alkaloids - bipleiophylline - pleiocarpamine - C-mavacurine - taberdivarine H - C-fluorocurine - biomimetic - oxidative couplingPublikationsverlauf
Eingereicht: 14. Juli 2023
Angenommen nach Revision: 23. August 2023
Artikel online veröffentlicht:
02. November 2023
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References
- 1 Biomimetic Organic Synthesis . Poupon E, Nay B. Wiley-VCH; Weinheim: 2011
- 2 Mauger A, Jarret M, Kouklovsky C, Poupon E, Evanno L, Vincent G. Nat. Prod. Rep. 2021; 38: 1852
- 3 Kam T.-S, Tan S.-J, Ng S.-W, Komiyama K. Org. Lett. 2008; 10: 3749
- 4a For structure determination, see: Hesse M, Philipsborn WV, Schumann D, Spiteller G, Spiteller-Friedmann M, Taylor WI, Schmid H, Karrer P. Helv. Chim. Acta 1964; 47: 878
- 4b Kump WG, Schmid H. Helv. Chim. Acta 1961; 44: 1503
- 4c Bartlett MF, Sklar R, Smith AF, Taylor WI. J. Org. Chem. 1963; 28: 2197
- 5a Benayad S, Beniddir MA, Evanno L, Poupon E. Eur. J. Org. Chem. 2015; 1894
- 5b Skiredj A, Beniddir MA, Evanno L, Poupon E. Eur. J. Org. Chem. 2016; 2954
- 5c Turpin V, Poupon E, Jullian J.-C, Evanno L. Eur. J. Org. Chem. 2020; 6989
- 5d Duchemin N, Skiredj A, Mansot J, Leblanc K, Vasseur J.-J, Beniddir MA, Evanno L, Poupon E, Smietana M, Arseniyadis S. Angew. Chem. Int. Ed. 2018; 57: 11786
- 5e Oger S, Duchemin N, Bendiab YM, Birlirakis N, Skiredj A, Rharrabti S, Jullian J.-C, Poupon E, Smietana M, Arseniyadis S, Evanno L. Chem. Commun. 2023; 59: 4221
- 6a Beaud R, Guillot R, Kouklovsky C, Vincent G. Angew. Chem. Int. Ed. 2012; 51: 12546
- 6b Tomakinian T, Guillot R, Kouklovsky C, Vincent G. Angew. Chem. Int. Ed. 2014; 53: 11881
- 6c Denizot N, Pouilhès A, Cucca M, Beaud R, Guillot R, Kouklovsky C, Vincent G. Org. Lett. 2014; 16: 5752
- 6d Beaud R, Tomakinian T, Denizot N, Pouilhès A, Kouklovsky C, Vincent G. Synlett 2015; 26: 432
- 6e Denizot N, Guillot R, Kouklovsky C, Vincent G. Chem. Eur. J. 2015; 21: 18953
- 6f Tomakinian T, Kouklovsky C, Vincent G. Synlett 2015; 26: 1269
- 6g Tomakinian T, Guillot R, Kouklovsky C, Vincent G. Chem. Commun. 2016; 52: 5443
- 6h Marques A.-S, Coeffard V, Chataigner I, Vincent G, Moreau X. Org. Lett. 2016; 18: 5296
- 6i Denizot N, Guillot R, Kouklovsky C, Vincent G. Synthesis 2018; 50: 4823
- 6j See also our Account on indole dearomatization: Abou-Hamdan H, Kouklovsky C, Vincent G. Synlett 2020; 31: 1775
- 7 Hanessian S, Giroux S, Merner BL. Design and Strategy in Organic Synthesis . Wiley-VCH; Weinheim: 2013
- 9 Dang T.-TT, Franke J, Carqueijeiro IS. T, Langley C, Courdavault V, O’Connor SE. Nat. Chem. Biol. 2018; 14: 760
- 10 Zhang L, Zhang C.-J, Zhang D.-B, Wen J, Zhao X.-W, Li Y, Gao K. Tetrahedron Lett. 2014; 55: 1815
- 11 Wenkert E, Wickberg B. J. Am. Chem. Soc. 1965; 87: 1580
- 12 Tatsis EC, Carqueijeiro I, de Bernonville TD, Franke J, Dang T.-TT, Oudin A, Lanoue A, Lafontaine F, Stavrinides AK, Clastre M, Courdavault V, O’Connor SE. Nat. Commun. 2017; 8: 316
- 13a For an alternative biosynthetic proposal for the mavacurans via an early N1–C16 bond formation, see: Pinar M, Hanaoka M, Hesse M, Schmid H. Helv. Chim. Acta 1971; 54: 15
- 13b For a process involving rearrangement of the akuammilan skeleton, see: Hugel G, Royer D, Le Men-Olivier L, Richard B, Jacquier M.-J, Lévy J. J. Org. Chem. 1997; 62: 578
- 14a Schmid H, Karrer P. Helv. Chim. Acta 1947; 30: 2081 ; for structure determination, see ref. 4a
- 15a 16-Hydroxymethylpleiocarpamine: Kan C, Deverre J.-R, Sevenet T, Quirion J.-C, Husson H.-P. Nat. Prod. Lett. 1995; 7: 275
- 15b 16-epi-Pleiocarpamine: Langlois N, Diatta L, Andriamialisoa RZ. Phytochemistry 1979; 18: 467
- 15c Normavacurine: Massiot G, Thépenier P, Jacquier M.-J, Le Men-Olivier L, Delaude C. Heterocycles 1989; 29: 1435
- 15d Taberdivarine H, Zhang B.-J, Teng X.-F, Bao M.-F, Zhong X.-H, Ni L, Cai X.-H. Phytochemistry 2015; 120: 46
- 15e C-Profluorocurine: Penelle J, Tits M, Christen P, Molgo J, Brandt V, Frédérich M, Angenot L. Phytochemistry 2000; 53: 1057
- 16a Burke DE, Le Quesne PW. J. Chem. Soc., Chem. Commun. 1972; 678
- 16b Burke DE, Cook JM, Le Quesne PW. J. Am. Chem. Soc. 1973; 95: 546
- 16c Bi Y, Cook JM, Le Quesne PW. Tetrahedron Lett. 1994; 35: 3877
- 16d Bi Y, Zhang L.-H, Hamaker LK, Cook JM. J. Am. Chem. Soc. 1994; 116: 9027
- 16e Gan T, Cook JM. Tetrahedron Lett. 1996; 37: 5037
- 16f Gan T, Cook JM. J. Org. Chem. 1998; 63: 1478
- 16g Plumocraline: Massiot G, Vercauteren J, Jacquier MJ, Lévy J, Le Men-Olivier L. C. R. Acad. Sci. Paris Sér. 2 1981; 292: 191
- 16h Pleiomaltinine: Ziegler RE, Tan S.-J, Kam T.-S, Porco JA. Angew. Chem. Int. Ed. 2012; 51: 9348
- 17a Lachkar D, Denizot N, Bernadat G, Ahamada K, Beniddir MA, Dumontet V, Gallard J.-F, Guillot R, Leblanc K, N’nang EO, Turpin V, Kouklovsky C, Poupon E, Evanno L, Vincent G. Nat. Chem. 2017; 9: 793
- 17b Denizot N, Lachkar D, Kouklovsky C, Poupon E, Evanno L, Vincent G. Synthesis 2018; 50: 4229
- 18 For the use of iron phthalocyanine [FePc] and t-BuOOH to perform the synthesis of isochromenoindolines, see: Ye J, Lin Y, Liu Q, Xu D, Wu F, Liu B, Gao Y, Chen H. Org. Lett. 2018; 20: 5457
- 19 For the isolation of voacalgine A and its misassigned structure, see: Hirasawa Y, Arai H, Rahman A, Kusumawati I, Zaini NC, Shirota O, Morita H. Tetrahedron 2013; 69: 10869
- 20a Sakai S, Shinma N. Heterocycles 1976; 4: 985
- 20b Sakai S, Shinma N. Yakugaku Zasshi 1978; 98: 950
- 21a Calverley MJ, Banks BJ, Harley-Mason J. Tetrahedron Lett. 1981; 22: 1635
- 21b Banks BJ, Calverley MJ, Edwards PD, Harley-Mason J. Tetrahedron Lett. 1981; 22: 1631
- 22 The group of Harley-Mason was also able to form the N1–C16 bond of the pentacycle of the mavacuran skeleton by a nucleophilic substitution on a simplified tetracyclic C16-mesylate lacking the ester at C16 and the C20-ethylidene and with a N4–C21 lactam, see: Calverley MJ, Harley-Mason J, Quarrie SA, Edwards PD. Tetrahedron 1981; 37: 1547
- 23 O’Rell DD, Lee FG. H, Boekelheide V. J. Am. Chem. Soc. 1972; 94: 3205
- 24a Jiménez J.-M, Zulaica E, Bennasar M.-L, Bosch J. J. Chem. Soc., Chem. Commun. 1993; 732
- 24b Bennasar ML, Zulaica E, Jimenez JM, Bosch J. J. Org. Chem. 1993; 58: 7756
- 25a Jarret M, Turpin V, Tap A, Gallard J.-F, Kouklovsky C, Poupon E, Vincent G, Evanno L. Angew. Chem. Int. Ed. 2019; 58: 9861
- 25b Jarret M, Tap A, Turpin V, Denizot N, Kouklovsky C, Poupon E, Evanno L, Vincent G. Eur. J. Org. Chem. 2020; 6340
- 26 Sato K, Kogure N, Kitajima M, Takayama H. Org. Lett. 2019; 21: 3342
- 27 Mauger A, Jarret M, Tap A, Perrin R, Guillot R, Kouklovsky C, Gandon V, Vincent G. Angew. Chem. Int. Ed. 2023; 62: e202302461
- 28a Martin SF, Clark CW, Ito M, Mortimore M. J. Am. Chem. Soc. 1996; 118: 9804
- 28b Ito M, Clark CW, Mortimore M, Goh JB, Martin SF. J. Am. Chem. Soc. 2001; 123: 8003
- 29a Kuehne ME, Hafter R. J. Org. Chem. 1978; 43: 3702
- 29b Vercauteren J, Massiot G, Levy J. J. Org. Chem. 1984; 49: 3230
- 29c Feldman PL, Rapoport H. J. Am. Chem. Soc. 1987; 109: 1603
- 30a Benayad S, Ahamada K, Lewin G, Evanno L, Poupon E. Eur. J. Org. Chem. 2016; 1494
- 30b Olivier L, Lévy J, Le Men J, Janot M.-M, Budzickiewicz M, Djerassi C. Bull. Soc. Chim. Fr. 1965; 3: 868
- 30c Pousset J.-L, Poisson J, Olivier L, Le Men J, Janot M.-M. C. R. Acad. Sci. Paris 1965; 261: 5538
- 30d Ahmad Y, Fatima K, Atta-ur-Rahman Atta-ur-Rahman, Occolowitz JL, Solheim BA, Clardy J, Garnick RL, Le Quesne PW. J. Am. Chem. Soc. 1977; 99: 1943
- 31a Zi W, Xie W, Ma D. J. Am. Chem. Soc. 2012; 134: 9126
- 31b Teng M, Zi W, Ma D. Angew. Chem. Int. Ed. 2014; 53: 1814
- 31c For an account on the indole-enolate oxidative coupling, see: Zi W, Zuo Z, Ma D. Acc. Chem. Res. 2015; 48: 702
- 32a Ren W, Tappin N, Wang Q, Zhu J. Synlett 2013; 24: 1941
- 32b Andres R, Wang Q, Zhu J. J. Am. Chem. Soc. 2020; 142: 14276 See also ref. 31b and
- 33 Jarret M, Abou-Hamdan H, Kouklovsky C, Poupon E, Evanno L, Vincent G. Org. Lett. 2021; 23: 1355
- 34 Jarret M, Tap A, Kouklovsky C, Poupon E, Evanno L, Vincent G. Angew. Chem. Int. Ed. 2018; 57: 12294
- 35a Martin SF, Chen KX, Eary CT. Org. Lett. 1999; 1: 79
- 35b Martin SF, Clark CW, Corbett JW. J. Org. Chem. 1995; 60: 3236
- 36 Yu S, Berner OM, Cook JM. J. Am. Chem. Soc. 2000; 122: 7827
- 37 Takayama H, Watanabe T, Seki H, Aimi N, Sakai S. Tetrahedron Lett. 1992; 33: 6831
- 38 Eckermann R, Gaich T. Chem. Eur. J. 2016; 22: 5749
- 39a Hannart JA. A. J. US Patent 4200638A, 1980
- 39b See also: Wanner MJ, Boots RN. A, Eradus B, de Gelder R, van Maarseveen JH, Hiemstra H. Org. Lett. 2009; 11: 2579
- 40 Saletu B, Grünberger J, Linzmayer L, Wittek R. Arch. Gerontol. Geriatr. 1984; 3: 127
- 41a Ren W, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2014; 53: 1818
- 41b Ren W, Wang Q, Zhu J. Angew. Chem. Int. Ed. 2016; 55: 3500
- 41c Ma J, Yin W, Zhou H, Liao X, Cook JM. J. Org. Chem. 2009; 74: 264
- 41d Yu F, Cheng B, Zhai HC. Org. Lett. 2011; 13: 5782
- 42 For a related radical-mediated approach leading to the total synthesis of vinoxine, see: Okada K, Ueda H, Tokuyama H. Org. Biomol. Chem. 2022; 20: 5943
- 43 Hunt DA. Org. Prep. Proced. Int. 1989; 21: 705
- 44a Nilsson Lill SO. Computational Perspectives on Organolithiums. In Lithium Compounds in Organic Synthesis: From Fundamentals to Applications. Luisi R, Capriati V. Wiley-VCH; Weinheim: 2014: 33
- 44b Hédouin M, Barthelemy A.-L, Vanthuyne N, Besrour H, Maddaluno J, Magnier E, Oulyadi H. Angew. Chem. Int. Ed. 2023; 62: e202214106
- 44c Barozzino-Consiglio G, Yuan Y, Fressigné C, Harrison-Marchand A, Oulyadi H, Maddaluno J. Organometallics 2015; 34: 4441
- 44d Ramachandran B, Kharidehal P, Pratt LM, Voit S, Okeke FN, Ewan M. J. Phys. Chem. A 2010; 114: 8423
- 45a Williams RM, Glinka T, Kwast E. J. Am. Chem. Soc. 1988; 110: 5927
- 45b Güller R, Borschberg H.-J. Helv. Chim. Acta 1993; 76: 1847
- 45c Godfrey RC, Green NJ, Nichol GS, Lawrence AL. Nat. Chem. 2020; 12: 615
- 45d For a review, see: Dhote PS, Patel P, Vanka K, Ramana CV. Org. Biomol. Chem. 2021; 19: 7970
- 46 While at the time the structures of the mavacuran alkaloids were not correctly assigned, the dihydroxylation of C-mavacurine into C-profluorocurine with PtO2 and O2 and the pinacol rearrangement of the latter into C-fluorocurine with HCl in methanol were reported in 1958, see: Fritz H, Mitarbeit TW. U, Besch E. Justus Liebigs Ann. Chem. 1958; 611: 268
- 47 Okada K, Ojima K, Ueda H, Tokuyama H. J. Am. Chem. Soc. 2023; 145: 16337
For isolation, see:
For isolation, see:
For the isolation of some of the mavacuran alkaloids, see:
Hemisyntheses of villastonine:
Macrocarpamine:
For selected DFT studies of organolithium reagents, see:
For selected dihydroxylation of indoles and subsequent pinacol rearrangement towards the pseudo-indoxyl-moiety, see: