Total Synthesis of Mavacuran Alkaloids via Bioinspired and Non-Bioinspired Strategies

Cyrille Kouklovsky; Erwan Poupon; Laurent Evanno; Guillaume Vincent

doi:10.1055/s-0042-1751498

Synlett, Table of Contents

Synlett 2024; 35(05): 521-534
DOI: 10.1055/s-0042-1751498

account

Biomimetic Synthesis

Total Synthesis of Mavacuran Alkaloids via Bioinspired and Non-Bioinspired Strategies

Cyrille Kouklovsky

^aInstitut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), Université Paris-Saclay, CNRS, Bâtiment Henri Moissan, 17 Avenue des Sciences, 91400 Orsay, France

,

Erwan Poupon ∗

^bBioCIS, Université Paris-Saclay, CNRS, Bâtiment Henri Moissan, 17 Avenue des Sciences, 91400 Orsay, France

,

Laurent Evanno ∗

^bBioCIS, Université Paris-Saclay, CNRS, Bâtiment Henri Moissan, 17 Avenue des Sciences, 91400 Orsay, France

,

Guillaume Vincent ∗

^aInstitut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), Université Paris-Saclay, CNRS, Bâtiment Henri Moissan, 17 Avenue des Sciences, 91400 Orsay, France

› Author Affiliations

Abstract

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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 coupling

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References

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

For isolation, see:

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

8a O’Connor SE, Maresh JJ. Nat. Prod. Rep. 2006; 23: 532
8b Szabó LF. Molecules 2008; 13: 1875

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

For isolation, see:

14a Schmid H, Karrer P. Helv. Chim. Acta 1947; 30: 2081 ; for structure determination, see ref. 4a

For the isolation of some of the mavacuran alkaloids, see:

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

Hemisyntheses of villastonine:

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

Macrocarpamine:

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

For selected DFT studies of organolithium reagents, see:

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

For selected dihydroxylation of indoles and subsequent pinacol rearrangement towards the pseudo-indoxyl-moiety, see:

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