Skip to main content
SpringerLink
Log in

Highly stereoselective construction of polycyclic benzofused tropane scaffolds and their latent bioactivities: bifunctional phosphonium salt-enabled cyclodearomatization process

  • Articles
  • Published:
Science China Chemistry Aims and scope Submit manuscript

Abstract

Structurally fused heterocycles encompassing a centerpiece of benzotropane are significant scaffolds with a plethora of promising biological activities, but such molecular architectures pose a long-standing daunting synthetic challenge. Herein, we reported a highly efficient asymmetric cyclodearomatization of 2-nitrobenzofurans with cyclic azomethine ylides by employing bifunctional phosphonium salts as phase-transfer catalysts. Under optimized reaction conditions, a diverse array of polycyclic benzofused tropane derivatives with four contiguous 4°/3° stereocenters were readily synthesized in both high yields and diastereoselectivities with up to >99% ee. The practicality and utility of this protocol were further demonstrated by the scaled-up reaction and facile elaborations. Moreover, preliminary investigations into their antitumor activities were also presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bur SK, Padwa A. Chem Rev, 2004, 104: 2401–2432

    PubMed  CAS  Google Scholar 

  2. D’Souza DM, Müller TJJ. Chem Soc Rev, 2007, 36: 1095–1108

    PubMed  Google Scholar 

  3. Blunt JW, Copp BR, Keyzers RA, Munro MH., Prinsep MR. Nat Prod Rep, 2012, 29: 144–222

    PubMed  CAS  Google Scholar 

  4. Stark H, Kathmann M, Schlicker E, Schunack W, Schlegel B, Sippl W. MRMC, 2004, 4: 965–977

    CAS  Google Scholar 

  5. Scott JD, Williams RM. Chem Rev, 2002, 102: 1669–1730

    PubMed  CAS  Google Scholar 

  6. Alvarez-Corral M, Munoz-Dorado M, Rodriguez-Garcia I. Chem Rev, 2008, 108: 3174–3198

    PubMed  CAS  Google Scholar 

  7. Katritzky AR, Rachwal S. Chem Rev, 2011, 111: 7063–7120

    PubMed  CAS  Google Scholar 

  8. Lewis JC, Bergman RG, Ellman JA. Acc Chem Res, 2008, 41: 1013–1025

    PubMed  PubMed Central  CAS  Google Scholar 

  9. Lu LQ, Chen JR, Xiao WJ. Acc Chem Res, 2012, 45: 1278–1293

    PubMed  CAS  Google Scholar 

  10. Marson CM. Chem Soc Rev, 2012, 41: 7712–7722

    PubMed  CAS  Google Scholar 

  11. Schreiber SL. Science, 2000, 287: 1964–1969

    PubMed  CAS  Google Scholar 

  12. Fodor G, Dharanipragada R. Nat Prod Rep, 1994, 11: 443–450

    PubMed  CAS  Google Scholar 

  13. Kohnen-Johannsen KL, Kayser O. Molecules, 2019, 24: 796–818

    PubMed Central  Google Scholar 

  14. Grynkiewicz G, Gadzikowska M. Pharmacol Rep, 2008, 60: 439–462

    PubMed  CAS  Google Scholar 

  15. Afewerki S, Wang JX, Liao WW, Córdova A. The Alkaloids: Chemistry and Biology, 2019, 81: 151–233

    PubMed  CAS  Google Scholar 

  16. Monn JA, Thurkauf A, Mattson MV, Jacobson AE, Rice KC. J Med Chem, 1990, 33: 1069–1076

    PubMed  CAS  Google Scholar 

  17. Humphrey AJ, O’ Hagan D. Nat Prod Rep, 2001, 18: 494–502

    PubMed  CAS  Google Scholar 

  18. Pollini GP, Benetti S, De Risi C, Zanirato V. Chem Rev, 2006, 106: 2434–2454

    PubMed  CAS  Google Scholar 

  19. Schultz DM, Wolfe JP. Org Lett, 2011, 13: 2962–2965

    PubMed  PubMed Central  CAS  Google Scholar 

  20. Narayan R, Bauer JO, Strohmann C, Antonchick AP, Waldmann H. Angew Chem Int Ed, 2013, 52: 12892–12896

    CAS  Google Scholar 

  21. Jia ZJ, Shan G, Daniliuc CG, Antonchick AP, Waldmann H. Angew Chem Int Ed, 2018, 57: 14493–14497

    CAS  Google Scholar 

  22. Wang Z, Wang DC, Xie MS, Qu GR, Guo HM. Org Lett, 2020, 22: 164–167

    PubMed  CAS  Google Scholar 

  23. Liang L, Niu HY, Wang DC, Yang XH, Qu GR, Guo HM. Chem Commun, 2019, 55: 553–556

    CAS  Google Scholar 

  24. Tan TD, Zhu XQ, Bu HZ, Deng G, Chen YB, Liu RS, Ye LW. Angew Chem Int Ed, 2019, 58: 9632–9639

    CAS  Google Scholar 

  25. Xu JH, Zheng SC, Zhang JW, Liu XY, Tan B. Angew Chem Int Ed, 2016, 55: 11834–11839

    CAS  Google Scholar 

  26. Lygo B, Andrews BI. Acc Chem Res, 2004, 37: 518–525

    PubMed  CAS  Google Scholar 

  27. Ooi T, Maruoka K. Acc Chem Res, 2004, 37: 526–533

    PubMed  CAS  Google Scholar 

  28. Manabe K. Tetrahedron, 1998, 54: 14465–14476

    CAS  Google Scholar 

  29. Manabe K. Tetrahedron Lett, 1998, 39: 5807–5810

    CAS  Google Scholar 

  30. Uraguchi D, Sakaki S, Ooi T. J Am Chem Soc, 2007, 129: 12392–12393

    PubMed  CAS  Google Scholar 

  31. Uraguchi D, Ueki Y, Ooi T. J Am Chem Soc, 2008, 130: 14088–14089

    PubMed  CAS  Google Scholar 

  32. Uraguchi D, Nakashima D, Ooi T. J Am Chem Soc, 2009, 131: 7242–7243

    PubMed  CAS  Google Scholar 

  33. Uraguchi D, Ito T, Ooi T. J Am Chem Soc, 2009, 131: 3836–3837

    PubMed  CAS  Google Scholar 

  34. Uraguchi D, Asai Y, Ooi T. Angew Chem Int Ed, 2009, 48: 733–737

    CAS  Google Scholar 

  35. Uraguchi D, Kinoshita N, Kizu T, Ooi T. J Am Chem Soc, 2015, 137: 13768–13771

    PubMed  CAS  Google Scholar 

  36. He R, Wang X, Hashimoto T, Maruoka K. Angew Chem Int Ed, 2008, 47: 9466–9468

    CAS  Google Scholar 

  37. He R, Ding C, Maruoka K. Angew Chem Int Ed, 2009, 48: 4559–4561

    CAS  Google Scholar 

  38. Shirakawa S, Kasai A, Tokuda T, Maruoka K. Chem Sci, 2013, 4: 2248–2252

    CAS  Google Scholar 

  39. Shirakawa S, Koga K, Tokuda T, Yamamoto K, Maruoka K. Angew Chem Int Ed, 2014, 53: 6220–6223

    CAS  Google Scholar 

  40. Werner T. Adv Synth Catal, 2009, 351: 1469–1481

    CAS  Google Scholar 

  41. Golandaj A, Ahmad A, Ramjugernath D. Adv Synth Catal, 2017, 359: 3676–3706

    CAS  Google Scholar 

  42. Enders D, Nguyen TV. Org Biomol Chem, 2012, 10: 5327–5331

    PubMed  CAS  Google Scholar 

  43. Liu S, Kumatabara Y, Shirakawa S. Green Chem, 2016, 18: 331–341

    CAS  Google Scholar 

  44. Cao D, Chai Z, Zhang J, Ye Z, Xiao H, Wang H, Chen J, Wu X, Zhao G. Chem Commun, 2013, 49: 5972–5974

    CAS  Google Scholar 

  45. Wu X, Liu Q, Liu Y, Wang Q, Zhang Y, Chen J, Cao W, Zhao G. Adv Synth Catal, 2013, 355: 2701–2706

    CAS  Google Scholar 

  46. Cao D, Zhang J, Wang H, Zhao G. Chem Eur J, 2015, 21: 9998–10002

    PubMed  CAS  Google Scholar 

  47. Ge L, Lu X, Cheng C, Chen J, Cao W, Wu X, Zhao G. J Org Chem, 2016, 81: 9315–9325

    PubMed  CAS  Google Scholar 

  48. Wang H, Wang K, Ren Y, Li N, Tang B, Zhao G. Adv Synth Catal, 2017, 359: 1819–1824

    CAS  Google Scholar 

  49. Cheng C, Lu X, Ge L, Chen J, Cao W, Wu X, Zhao G. Org Chem Front, 2017, 4: 101–114

    CAS  Google Scholar 

  50. Wang H, Zheng C, Zhao G. Chin J Chem, 2019, 37: 1111–1119

    CAS  Google Scholar 

  51. Pan J, Wu JH, Zhang H, Ren X, Tan JP, Zhu L, Zhang HS, Jiang C, Wang T. Angew Chem Int Ed, 2019, 58: 7425–7430

    CAS  Google Scholar 

  52. Tan JP, Yu P, Wu JH, Chen Y, Pan J, Jiang C, Ren X, Zhang HS, Wang T. Org Lett, 2019, 21: 7298–7302

    PubMed  CAS  Google Scholar 

  53. Zhang S, Yu X, Pan J, Jiang C, Zhang H, Wang T. Org Chem Front, 2019, 6: 3799–3803

    CAS  Google Scholar 

  54. Zhu L, Ren X, Liao Z, Pan J, Jiang C, Wang T. Org Lett, 2019, 21: 8667–8672

    PubMed  CAS  Google Scholar 

  55. Wu JH, Pan J, Du J, Wang X, Wang X, Jiang C, Wang T. Org Lett, 2020, 22: 395–399

    PubMed  CAS  Google Scholar 

  56. Tan J, Zhang H, Jiang Z, Chen Y, Ren X, Jiang C, Wang T. Adv Synth Catal, 2020, 362: 1058–1063

    CAS  Google Scholar 

  57. Liu X, Lu D, Wu J, Tan J, Jiang C, Gao G, Wang T. Adv Synth Catal, 2020, 362: 1490–1495

    CAS  Google Scholar 

  58. See Supporting Information online (SI) for details

  59. CCDC 1935767 (3l) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Date Centre

  60. Vivanco S, Lecea B, Arrieta A, Prieto P, Morao I, Linden A, Cossío FP. J Am Chem Soc, 2000, 122: 6078–6092

    CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (21971165, 21921002, 81630101), the National Key Research and Development Program of China (2018YFA0903500), the “1000-Youth Talents Program” (YJ201702) and the Fundamental Research Funds for the Central Universities. We also acknowledge the comprehensive training platform of the Specialized Laboratory in the College of Chemistry at Sichuan University and the Analytical & Testing Center of Sichuan University for compound testing.

Author information

Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Green Chemistry & Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, China

    Jian-Ping Tan, Yuan Chen, Xianle Rong, Lixiang Zhu, Chunhui Jiang & Tianli Wang

  2. National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610064, China

    Xiaojie Li & Kai Xiao

  3. School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, China

    Chunhui Jiang

Authors
  1. Jian-Ping Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaojie Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xianle Rong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lixiang Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chunhui Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kai Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tianli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tianli Wang.

Ethics declarations

Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Dedicated to Professor Albert S. C. Chan on the occasion of his 70th birthday.

Supporting Information

11426_2020_9754_MOESM1_ESM.pdf

Highly Stereoselective Construction of Polycyclic Benzofused Tropane Scaffolds and Their Latent Bioactivities: Bifunctional Phosphonium Salt-enabled Cyclodearomatization Process

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, JP., Li, X., Chen, Y. et al. Highly stereoselective construction of polycyclic benzofused tropane scaffolds and their latent bioactivities: bifunctional phosphonium salt-enabled cyclodearomatization process. Sci. China Chem. 63, 1091–1099 (2020). https://doi.org/10.1007/s11426-020-9754-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11426-020-9754-7

Keywords

Search

Navigation