RSS-Feed abonnieren
DOI: 10.1055/a-2107-5159
Concise Total Synthesis of Complanadine A Enabled by Pyrrole-to-Pyridine Molecular Editing
This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health (GM128570).
Abstract
The Lycopodium alkaloid complanadine A, isolated in 2000, is a complex and unsymmetrical dimer of lycodine. Biologically, it is a novel and promising lead compound for the development of new treatments for neurodegenerative disorders and persistent pain management. Herein, we report a concise synthesis of complanadine A using a pyrrole-to-pyridine molecular editing strategy. The use of a nucleophilic pyrrole as the precursor of the desired pyridine enabled an efficient and one-pot construction of the tetracyclic core skeleton of complanadine A and lycodine. The pyrrole group was converted into a 3-chloropyridine via Ciamician–Dennstedt one-carbon ring expansion. A subsequent C–H arylation between the 3-chloropyridine and a pyridine N-oxide formed the unsymmetrical dimer, which was then advanced to complanadine A. Overall, from a readily available known compound, the total synthesis of complanadine A was achieved in 11 steps. The pyrrole-to-pyridine molecular editing strategy enabled us to significantly enhance the overall synthetic efficiency. Additionally, as demonstrated by Suzuki–Miyaura cross-coupling, the 3-chloropyridine product from the Ciamician–Dennstedt rearrangement is amenable for further derivatization, offering an opportunity for simplified analogue synthesis.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2107-5159.
- Supporting Information
Publikationsverlauf
Eingereicht: 15. Februar 2023
Angenommen nach Revision: 07. Juni 2023
Accepted Manuscript online:
07. Juni 2023
Artikel online veröffentlicht:
03. Juli 2023
© 2023. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Ma X, Gang DR. Nat. Prod. Rep. 2004; 21: 752
- 2a Zhang H.-Y. Acta Pharmacol. Sin. 2012; 33: 1170
- 2b Herzon SB, Tun MK. M. J. Exp. Pharmacol. 2012; 4: 113
- 3 Kobayashi J, Hirasawa Y, Yoshida N, Morita H. Tetrahedron Lett. 2000; 41: 9069
- 4a Morita H, Ishiuchi K, Haganuma A, Hoshino T, Obara Y, Nakahata N, Kobayashi J. Tetrahedron 2005; 61: 1955
- 4b Ishiuchi K, Kubota T, Ishiyama H, Hayashi S, Shibata T, Mori K, Obara Y, Nakahata N, Kobayashi J. Bioorg. Med. Chem. 2011; 19: 749
- 4c Ishiuchi K, Kubota T, Mikami Y, Obara Y, Nakahata N, Kobayashi J. Bioorg. Med. Chem. 2007; 15: 413
- 5a Ishiuchi K, Kubota T, Hayashi S, Shibata T, Kobayashi J. Tetrahedron Lett. 2009; 50: 4221
- 5b Yeap JS.-Y, Lim K.-H, Yong K.-T, Lim S.-H, Kam T.-S, Low Y.-Y. J. Nat. Prod. 2019; 82: 324
- 5c Haley HM. S, Payer SE, Papidocha SM, Clemens S, Nyenhuis J, Sarpong R. J. Am. Chem. Soc. 2021; 143: 4732
- 6a Yuan C, Chang C.-T, Axelrod A, Siegel D. J. Am. Chem. Soc. 2010; 132: 5924
- 6b Yuan C, Chang C.-T, Siegel D. J. Org. Chem. 2013; 78: 5647
- 7 Johnson T, Siegel D. Bioorg. Med. Chem. Lett. 2014; 24: 3512
- 8 Wang J, Zhang Z.-K, Jiang F.-F, Qi B.-W, Ding N, Hnin SY. Y, Liu X, Li J, Wang X.-H, Tu P.-F, Abe I, Morita H, Shi S.-P. Org. Lett. 2020; 22: 8725
- 9a Fischer DF, Sarpong R. J. Am. Chem. Soc. 2010; 132: 5926
- 9b Newton JN, Fischer DF, Sarpong R. Angew. Chem. Int. Ed. 2013; 52: 1726
- 10a Ishiyama T, Takagi J, Ishida K, Miyaura N, Anastasi NR, Hartwig JF. J. Am. Chem. Soc. 2002; 124: 390
- 10b Cho J.-Y, Tse MK, Holmes D, Maleczka RE. Jr, Smith MR. Science 2002; 295: 305
- 11 Zhao L, Tsukano C, Kwon E, Takemoto Y, Hirama M. Angew. Chem. Int. Ed. 2013; 52: 1722
- 12 Yang Y, Haskins CW, Zhang W, Low PL, Dai M. Angew. Chem. Int. Ed. 2014; 53: 3922
- 13 Ma D, Martin BS, Gallagher KS, Saito T, Dai M. J. Am. Chem. Soc. 2021; 143: 16383
- 14 Jurczyk J, Woo J, Kim SF, Dherange BD, Sarpong R, Levin MD. Nat. Synth. 2022; 1: 352
- 15 Ciamician GL, Dennstedt M. Ber. Dtsch. Chem. Ges. 1881; 14: 1153
- 16a Yang Y, Bai Y, Sun S, Dai M. Org. Lett. 2014; 16: 6216
- 16b Nakahara K, Hirano K, Maehata R, Kita Y, Fujioka H. Org. Lett. 2011; 13: 2015
- 16c Chen J, Forsyth CJ. Org. Lett. 2003; 5: 1281
- 17 Meng L. J. Org. Chem. 2016; 81: 7784
- 18 Linghu X, Kennedy-Smith JJ, Toste FD. Angew. Chem. Int. Ed. 2007; 46: 7671
- 19a Poon KW. C, House SE, Dudley GB. Synlett 2005; 3142
- 19b Poon KW. C, Dudley GB. J. Org. Chem. 2006; 71: 3923
- 20 Del Bel M, Rovira A, Guerrero CA. J. Am. Chem. Soc. 2013; 135: 12188
- 21 Thangaraj M, Gaykar RN, Roy T, Biju AT. J. Org. Chem. 2017; 82: 4470
- 22 Sudhakar G, Kadam VD, Bayya S, Pranitha G, Jagadeesh B. Org. Lett. 2011; 13: 5452
- 23 Li H, Shen S.-J, Zhu C.-L, Xu H. J. Am. Chem. Soc. 2019; 141: 9415
- 24 Li X, Chen P, Liu G. Sci. China: Chem. 2019; 62: 1537
- 25 Aube J, Milligan GL. J. Am. Chem. Soc. 1991; 113: 8965
- 26 Zhao W, Sun J. Chem. Rev. 2018; 118: 10439
- 27a Dhanak D, Reese C. J. Chem. Soc., Perkin Trans. 1 1987; 2829
- 27b Raheem IT, Thiara PS, Jacobsen EN. Org. Lett. 2008; 10: 1577
- 27c Dherange BD, Kelly PQ, Liles JP, Sigman MS, Levin MD. J. Am. Chem. Soc. 2021; 143: 11337
- 28 Wynberg H. Chem. Rev. 1960; 60: 169
- 29 Campeau L.-C, Schipper DJ, Fagnou K. J. Am. Chem. Soc. 2008; 130: 3266
- 30 Welin ER, Ngamnithiporn A, Klatte M, Lapointe G, Pototschnig GM, McDermott MS. J, Conklin D, Gilmore CD, Tadross PM, Haley CK, Negoro K, Glibstrup E, Grünanger CU, Allan KM, Virgil SC, Slamon DJ, Stoltz BM. Science 2019; 363: 270
- 31a Heathcock CH, Kleinman EF, Binkley ES. J. Am. Chem. Soc. 1982; 104: 1054
- 31b Zhao L, Tsukano C, Kown E, Shirakawa H, Kaneko S, Takemoto Y, Hiram M. Chem. Eur. J. 2017; 23: 802
- 31c Azuma M, Yoshikawa T, Kogure N, Kitajima M, Takayama H. J. Am. Chem. Soc. 2014; 136: 11618
- 32 Hu Y, Shi H, Zhou M, Ren Q, Zhu W, Zhang W, Zhang Z, Zhou C, Liu Y, Ding X, Shen HC, Yan SF, Dey F, Wu W, Zhai G, Zhou Z, Xu Z, Ji Y, Lv H, Jiang T, Wang W, Xu Y, Vercruysse M, Yao X, Mao Y, Yu X, Bradley K, Tan X. J. Med. Chem. 2020; 63: 9623