Citation: Jun-Gang Wang, Bing-Yi Zhou, Yao-Luo Hu, Yong-Dong Du, Rong-He Wu, Chun-Yan Wu, Wen-Chao Yang, An-Xin Wu. Atom-swapping skeletal editing of benzo[c]oxepines for the construction of 2-benzodiazepines via a continuous manufacturing one-pot synthesis[J]. Chinese Chemical Letters, ;2026, 37(4): 111200. doi: 10.1016/j.cclet.2025.111200 shu

Atom-swapping skeletal editing of benzo[c]oxepines for the construction of 2-benzodiazepines via a continuous manufacturing one-pot synthesis

Jun-Gang Wang ^{a, b, 1} ,
Bing-Yi Zhou ^{a, 1} ,
Yao-Luo Hu ^b ,
Yong-Dong Du ^b ,
Rong-He Wu ^b ,
Chun-Yan Wu ^c ,
Wen-Chao Yang ^{a, *,} ,
An-Xin Wu ^{c, *,}

a.
State Key Laboratory of Green Pesticide, Guizhou University, Guiyang 550025, China
b.
School of Chemical Engineering, Guizhou Minzu University, Guiyang 550025, China
c.
State Key Laboratory of Green Pesticide, International Joint Research Center for Intelligent Biosensor Technology and Health, College of Chemistry, Central China Normal University, Wuhan 430079, China

wcyang@gzu.edu.cn

chwuax@mail.ccnu.edu.cn

Received Date: 19 January 2025
Revised Date: 29 March 2025
Accepted Date: 11 April 2025
Available Online: 11 April 2025

Figures(5)

An efficient skeletal editing for the construction of 2-benzodiazepines from benzo[c]oxepines was developed through atom-swapping of oxygen atom to the nitrogen atom. This reaction integrated the sequential ring-opening/substitution/ring-closing in the continuous manufacturing one-pot synthesis. The reaction conditions are mild, transition metal-free, simple-operated and the substrates are widely applicable. The anti-tumor activity of some synthesized 2-benzodiazepine compounds shows this atom-swapping skeletal editing through the deconstruction-reconstruction of heterocycles is attractive and effective in the discovery of new drug skeletons.
- Skeletal editing,
- Atom-swapping,
- 2-Benzodiazepines,
- Benzo[c]oxepines,
- One-pot synthesis
1. [1]
  D.A. Horton, G.T. Bourne, M.L. Smythe, Chem. Rev. 103 (2003) 893–930. doi: 10.1021/cr020033s
2. [2]
  R.D. Taylor, M. MacCoss, A.D.G. Lawson, J. Med. Chem. 57 (2014) 5845–5859. doi: 10.1021/jm4017625
3. [3]
  J. Jurczyk, J. Woo, S.F. Kim, et al., Nat. Synth. 1 (2022) 352–364. doi: 10.1038/s44160-022-00052-1
4. [4]
  J.B. Roque, Y. Kuroda, L.T. Göttemann, R. Sarpong, Nature 564 (2018) 244–248. doi: 10.1038/s41586-018-0700-3
5. [5]
  J. Woo, A.H. Christian, S.A. Burgess, et al., Science 376 (2022) 527–532. doi: 10.1126/science.abo4282
6. [6]
  B. Roure, M. Alonso, G. Lonardi, et al., Nature 637 (2024) 860–867.
7. [7]
  Á. Rentería-Gómez, O. Gutierrez, Nature 631 (2024) 30–31. doi: 10.1038/d41586-024-02017-0
8. [8]
  F. Ficarra, M. Silvi, Nature 623 (2023) 36–37. doi: 10.1038/d41586-023-03297-8
9. [9]
  M. Sicignano, P. Costa, Nat. Catal. 7 (2024) 224–226.
10. [10]
  E. Li, C.W. Lindsley, J. Chang, B. Yu, J. Med. Chem. 67 (2024) 13509–13511. doi: 10.1021/acs.jmedchem.4c01841
11. [11]
  B.W. Joynson, L.T. Ball, Helv. Chim. Acta 106 (2023) e202200182. doi: 10.1002/hlca.202200182
12. [12]
  T. Heilmann, J.M. Lopez-Soria, J. Ulbrich, et al., Angew. Chem. Int. Ed. 63 (2024) e202403826. doi: 10.1002/anie.202403826
13. [13]
  J. Wang, H. Lu, Y. He, et al., J. Am. Chem. Soc. 144 (2022) 22433–22439. doi: 10.1021/jacs.2c10570
14. [14]
  L. Wu, H. Xia, J. Bai, et al., Nat. Chem. 16 (2024) 1951–1959. doi: 10.1038/s41557-024-01668-w
15. [15]
  Z. Liu, X. Zhang, P. Sivaguru, X. Bi, Acc. Chem. Res. 58 (2025) 130–149. doi: 10.1021/acs.accounts.4c00709
16. [16]
  Z. Liu, P. Sivaguru, Y. Ning, et al., Chem. Eur. J. 29 (2023) e202301227. doi: 10.1002/chem.202301227
17. [17]
  X. Ma, J. Su, Q. Song, Acc. Chem. Res. 56 (2023) 592–607. doi: 10.1021/acs.accounts.2c00830
18. [18]
  F. Wu, C.C. Chintawar, R. Lalisse, et al., Nat. Catal. 7 (2024) 242–251. doi: 10.1038/s41929-023-01089-x
19. [19]
  S. Liu, Y. Yang, Q. Song, et al., Nat. Chem. 16 (2024) 988–997. doi: 10.1038/s41557-024-01468-2
20. [20]
  Y. Yang, Q. Song, P. Sivaguru, et al., Angew. Chem. Int. Ed. 63 (2024) e202401359. doi: 10.1002/anie.202401359
21. [21]
  E.E. Hyland, P.Q. Kelly, A.M. Mckillop, et al., J. Am. Chem. Soc. 144 (2022) 19258–19264. doi: 10.1021/jacs.2c09616
22. [22]
  Y. Xu, S. Xiang, J. Che, et al., Chin. J. Chem. 42 (2024) 2656–2667. doi: 10.1002/cjoc.202400342
23. [23]
  J.C. Reisenbauer, O. Green, A. Franchino, et al., Science 377 (2022) 1104–1109. doi: 10.1126/science.add1383
24. [24]
  G.L. Bartholomew, F. Carpaneto, R. Sarpong, J. Am. Chem. Soc. 144 (2022) 22309–22315. doi: 10.1021/jacs.2c10746
25. [25]
  S.H. Kennedy, B.D. Dherange, K.J. Berger, M.D. Levin, Nature 593 (2021) 223–227. doi: 10.1038/s41586-021-03448-9
26. [26]
  H. Qin, W. Cai, S. Wang, et al., Angew. Chem. Int. Ed. 60 (2021) 20678–20683. doi: 10.1002/anie.202107356
27. [27]
  J. Jurczyk, M.C. Lux, D. Adpressa, et al., Science 373 (2021) 1004–1012. doi: 10.1126/science.abi7183
28. [28]
  J. Luo, Q. Zhou, Z. Xu, et al., J. Am. Chem. Soc. 146 (2024) 21389–21400. doi: 10.1021/jacs.4c03713
29. [29]
  E.Y. Lai, L. Guillemard, Nat. Rev. Chem. 7 (2023) 71. doi: 10.1038/s41570-023-00465-2
30. [30]
  Q.H. Luu, J. Li, Chem. Sci. 13 (2022) 1095–1100. doi: 10.1039/d1sc06968c
31. [31]
  S.C. Patel, N.Z. Burns, J. Am. Chem. Soc. 144 (2022) 17797–17802. doi: 10.1021/jacs.2c08464
32. [32]
  H. Lu, Y. Zhang, X.H. Wang, et al., Nat. Commun. 15 (2024) 3772. doi: 10.1038/s41467-024-48265-6
33. [33]
  T. Wang, C. Li, J. Mi, et al., CCS Chem. 7 (2025) 392–402. doi: 10.31635/ccschem.024.202404133
34. [34]
  Q. Cheng, D. Bhattacharya, M. Haring, et al., Nat. Chem. 16 (2024) 741–748. doi: 10.1038/s41557-023-01428-2
35. [35]
  T. Morofuji, K. Inagawa, N. Kano, Org. Lett. 23 (2021) 6126–6130. doi: 10.1021/acs.orglett.1c02225
36. [36]
  B.J.H. Uhlenbruck, C.M. Josephitis, L. Lescure, et al., Nature 631 (2024) 87–93. doi: 10.1038/s41586-024-07474-1
37. [37]
  D. Kim, J. You, D.H. Lee, et al., Science 386 (2024) 99–105. doi: 10.1126/science.adq6245
38. [38]
  S. Masaki, A. Yoshio, O. Tomohiro, et al., Chem. Pharm. Bull. 52 (2004) 577–590. doi: 10.1248/cpb.52.577
39. [39]
  H.E. Pelish, N.J. Westwood, Y. Feng, et al., J. Am. Chem. Soc. 123 (2001) 6740–6741. doi: 10.1021/ja016093h
40. [40]
  M. Berglund, M.F. Dalence-Guzmán, S. Skogvall, O. Sterner, Bioorg. Med. Chem. 16 (2008) 2529–2540. doi: 10.1016/j.bmc.2007.11.056
41. [41]
  C. Hang, A. Ramirez, C. Chan, et al., ACS Catal. 11 (2021) 2460–2472. doi: 10.1021/acscatal.0c05533
42. [42]
  P.D. Johnson, P.A. Aristoff, G.E. Zurenko, et al., Bioorg. Med. Chem. Lett. 13 (2023) 4197–4200.
43. [43]
  C.D. Jesudason, L.S. Beavers, J.W. Cramer, et al., Bioorg. Med. Chem. Lett. 16 (2006) 3415–3418. doi: 10.1016/j.bmcl.2006.04.004
44. [44]
  N.E. Calcaterra, J.C. Barrow, ACS Chem. Neurosc. 5 (2014) 253–260. doi: 10.1021/cn5000056
45. [45]
  Á. Velasco-Rubio, J.A. Varela, C. Saá, Adv. Synth. Cat. 362 (2020) 4861–4875. doi: 10.1002/adsc.202000808
46. [46]
  T.O. Vieira, H. Alper, Org. Lett. 10 (2008) 485–487. doi: 10.1021/ol702933g
47. [47]
  A. Inyutina, D. Dar’in, G. Kantin, M. Krasavin, Org. Biomol. Chem. 19 (2021) 5068–5071. doi: 10.1039/d1ob00773d
48. [48]
  X. Vidal, J.L. Mascareas, M. Gulías, Org. Lett. 23 (2021) 5323–5328. doi: 10.1021/acs.orglett.1c01594
49. [49]
  A.K. Pandey, S.H. Han, N.K. Mishra, et al., ACS Catal. 8 (2018) 742–746. doi: 10.1021/acscatal.7b03812
50. [50]
  M. Virelli, E. Moroni, G. Colombo, et al., Chem. Eur. J. 2 (2018) 16516–16520. doi: 10.1002/chem.201804244
51. [51]
  K. Linkens, H.R. Schmidt, J.J. Sahn, et al., Eur. J. Med. Chem. 151 (2018) 557–567. doi: 10.1016/j.ejmech.2018.02.024
52. [52]
  M.J. Mailloux, G.S. Fleming, S.S. Kumta, A.B. Beeler, Org. Lett. 23 (2021) 525–529. doi: 10.1021/acs.orglett.0c04050
53. [53]
  N.C. Hsueh, K.T. Chen, M.Y. Chang, Adv. Synth. Catal. 364 (2022) 4110–4121. doi: 10.1002/adsc.202200914
54. [54]
  J. Wang, M. Wang, J. Xiang, et al., Org. Lett. 14 (2012) 6060–6063. doi: 10.1021/ol302950w
55. [55]
  J. Wang, M. Wang, J. Xiang, et al., Tetrahedron 71 (2015) 7687–7694. doi: 10.1016/j.tet.2015.07.062
56. [56]
  M. Wang, J. Wang, J. Xiang, A. Wu, Asian J. Org. Chem. 4 (2015) 741–744. doi: 10.1002/ajoc.201500123
57. [57]
  M. Wang, B.C. Tang, J.C. Xiang, et al., J. Org. Chem. 83 (2018) 3409–3416. doi: 10.1021/acs.joc.8b00126
58. [58]
  Y. Du, L. Ma, C. Wu, et al., J. Org. Chem. 89 (2024) 15953–15963. doi: 10.1021/acs.joc.4c02206
59. [59]
  Y. Zhou, S.G. Lei, B. Abudureheman, et al., Nat. Commun. 15 (2024) 10907. doi: 10.1038/s41467-024-55312-9
60. [60]
  R.D. Taylor, M. MacCoss, A.D. Lawson, J. Med. Chem. 60 (2017) 3552–3579. doi: 10.1021/acs.jmedchem.6b01807
61. [61]
  Luke. Rogers, K.F. Jensen, Green Chem. 21 (2019) 3481–3498. doi: 10.1039/c9gc00773c
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