Synlett 2024; 35(05): 593-597
DOI: 10.1055/a-2047-9680
cluster
Biomimetic Synthesis

Total Synthesis of 4α-Hydroxyallosecurinine and Securingine F, Securinega Alkaloids with a C4-Hydroxy Handle for Biofunctional Derivatizations

Sangbin Park
,
Doyoung Kim
,
Wooil Yang
,
Sunkyu Han  ∗
This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korea Government (MSIT) (No. NRF2021R1A2C2011203). We acknowledge support by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2018R1A5A1025208). This research was also supported by the KAIST KC30 project.
› Further Information
   Permissions and Reprints All articles of this category


This work is dedicated to Professor Hee-Yoon Lee (1957–2023) in memory of his scientific contributions to the field of total synthesis.

Abstract

We describe the first total synthesis of the C4-hydroxylated securinega alkaloids 4α-hydroxyallosecurinine and securingine F. The synthetic route features an Ellman’s light-mediated hydrogen-atom-transfer-based epimerization reaction that effectively sets the desired configuration at the C2 position. Simultaneous skeletal rearrangement from neosecurinane to securinane frameworks and stereochemical reversal at the C4 site was achieved under Mitsunobu reaction conditions. The C4-hydroxy group is envisioned to serve as a handle for potential biofunctional derivatizations.

Key words

total synthesis - securinega alkaloids - biofunctional derivatizations - hydroxyallosecurinine - securingine F

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2047-9680.
  • Supporting Information


Publication History

Received: 06 February 2023

Accepted after revision: 06 March 2023

Accepted Manuscript online:
06 March 2023

Article published online:
12 April 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References and Notes

  • 1 Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Nat. Rev. Drug Discovery 2021; 20: 200
    CrossrefPubMedSearch in Google Scholar
  • 2 Newman DJ, Cragg GM. J. Nat. Prod. 2020; 83: 770
    CrossrefPubMedSearch in Google Scholar
  • 3 Davis DC, Hoch DG, Wu L, Abegg D, Martin BS, Zhang Z.-Y, Adibekian A, Dai M. J. Am. Chem. Soc. 2018; 140: 17465
    CrossrefPubMedSearch in Google Scholar
  • 4 Spradlin JN, Hu X, Ward CC, Brittain SM, Jones MD, Ou L, To M, Proudfoot A, Ornelas E, Woldegiorgis M, Olzmann JA, Bussiere DE, Thomas JR, Tallarico JA, McKenna JM, Schirle M, Maimone TJ, Nomura DK. Nat. Chem. Biol. 2019; 15: 747
    CrossrefPubMedSearch in Google Scholar
  • 5 Cui C, Dwyer BG, Liu C, Abegg D, Cai Z.-J, Hoch DG, Yin X, Qiu N, Liu J.-Q, Adibekian A, Dai M. J. Am. Chem. Soc. 2021; 143: 4379
    CrossrefPubMedSearch in Google Scholar
  • 6 Abegg D, Tomanik M, Qiu N, Pechalrieu D, Shuster A, Commare B, Togni A, Herzon SB, Adibekian A. J. Am. Chem. Soc. 2021; 143: 20332
    CrossrefPubMedSearch in Google Scholar
  • 7 Fu Z, Li S, Han S, Shi C, Zhang Y. Signal Transduction Targeted Ther. 2022; 7: 93
    CrossrefPubMedSearch in Google Scholar
  • 8 Newman DJ. J. Nat. Prod. 2021; 84: 917
    CrossrefPubMedSearch in Google Scholar
  • 9 Wehlauch R, Gademann K. Asian J. Org. Chem. 2017; 6: 1146
    CrossrefSearch in Google Scholar
  • 10 Kang G, Park S, Han S. Eur. J. Org. Chem. 2021; 2021: 1508
    CrossrefSearch in Google Scholar
  • 11 Kang G, Park S, Han S. Acc. Chem. Res. 2023; 56: 140
    CrossrefPubMedSearch in Google Scholar
  • 12 Hou W, Huang H, Wu X.-Q, Lan J.-X. Biomed. Pharmacother. 2023; 158: 114190
    CrossrefPubMedSearch in Google Scholar
  • 13 Hou W, Wang Z.-Y, Peng C.-K, Lin J, Liu X, Chang Y.-Q, Xu J, Jiang R.-W, Lin H, Sun P.-H, Chen W.-M. Eur. J. Med. Chem. 2016; 122: 149
    CrossrefPubMedSearch in Google Scholar
  • 14 Hou W, Lin H, Wang Z.-Y, Banwell MG, Zeng T, Sun P.-H, Lin J, Chen W.-M. Med. Chem. Commun. 2017; 8: 320
    CrossrefPubMedSearch in Google Scholar
  • 15 Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga J.-Y, Im S.-A, Moore HC. F, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim S.-B, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA. N. Engl. J. Med. 2022; 387: 9
    CrossrefPubMedSearch in Google Scholar
  • 16 Wang G.-c, Wang Y, Zhang X.-q, Li Y.-l, Yao X.-s, Ye W.-c. Chem. Pharm. Bull. 2010; 58: 390
    CrossrefPubMedSearch in Google Scholar
  • 17 Park KJ, Kim CS, Khan Z, Oh J, Kim SY, Choi SU, Lee KR. J. Nat. Prod. 2019; 82: 1345
    CrossrefPubMedSearch in Google Scholar
  • 18 Ohsaki A, Ishiyama H, Yoneda K, Kobayashi J. Tetrahedron Lett. 2003; 44: 3097
    CrossrefSearch in Google Scholar
  • 19 Liu P, Hong S, Weinreb SM. J. Am. Chem. Soc. 2008; 130: 7562
    CrossrefPubMedSearch in Google Scholar
  • 20 Han H, Smith AB. III. Org. Lett. 2015; 17: 4232
    CrossrefPubMedSearch in Google Scholar
  • 21 Lee S, Kang G, Chung G, Kim D, Lee H.-Y, Han S. Angew. Chem. Int. Ed. 2020; 59: 6894
    CrossrefPubMedSearch in Google Scholar
  • 22 Han S. Bull. Korean Chem. Soc. 2022; 44: 172
    CrossrefSearch in Google Scholar
  • 23 Park S, Kang G, Kim C, Kim D, Han S. Nat. Commun. 2022; 13: 5149
    CrossrefPubMedSearch in Google Scholar
  • 24 Wehlauch R, Grendelmeier SM, Miyatake-Ondozabal H, Sandtorv AH, Scherer M, Gademann K. Org. Lett. 2017; 19: 548
    CrossrefPubMedSearch in Google Scholar
  • 25 Shen Z, Walker MM, Chen S, Parada GA, Chu DM, Dongbang S, Mayer JM, Houk KN, Ellman JA. J. Am. Chem. Soc. 2021; 143: 126
    CrossrefPubMedSearch in Google Scholar
  • 26 Kang G, Baik M.-H, Han S. Bull. Korean Chem. Soc. 2020; 42: 486
    CrossrefSearch in Google Scholar
  • 27 Kang G, Han S. J. Am. Chem. Soc. 2022; 144: 8932
    CrossrefPubMedSearch in Google Scholar
  • 28 (–)-Securingine F (5) mCPBA (77%, 3.6 mg, 0.0160 mmol, 1.1 equiv) was added to a solution of 4α-hydroxyallosecurinine (4) (3.4 mg, 0.0146 mmol, 1.0 equiv) in CH2Cl2 (1 mL) at 0 °C. After 5 min, K2CO3 (6.0 mg, 0.0437 mmol, 3.0 equiv) was added, and the resulting mixture was slowly warmed to 23 °C. After 4 h, the reaction was quenched with brine (5 mL) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3 × 10 mL) and the combined organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The resulting crude residue was purified by flash column chromatography [silica gel, CH2Cl2–acetone (6:1)] to give a white amorphous solid; yield: 2.6 mg (72%); Rf = 0.44 (UV, KMnO4); [α]D 25 –250.6 (c 0.1, MeOH) [Lit.4 −167.1 (c 0.1, MeOH)]. 1H NMR (400 MHz, CDCl3): δ = 6.86 (d, J = 9.4 Hz, 1 H), 6.29 (dd, J = 9.4, 5.8 Hz, 1 H), 5.83 (s, 1 H), 4.73 (dt, J = 5.8, 2.9 Hz, 1 H), 4.08–4.02 (m, 1 H), 3.30 (dd, J = 12.0, 2.6 Hz, 1 H), 3.07–2.95 (m, 2 H), 2.54 (dd, J = 11.5, 3.4 Hz, 1 H), 2.03 (dd, J = 11.4, 2.4 Hz, 1 H), 1.83 (dd, J = 13.7, 2.7 Hz, 1 H), 1.80–1.74 (m, 2 H), 1.18 (ddd, J = 14.0, 12.1, 2.7 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ = 172.1, 164.4, 134.6, 126.6, 113.6, 82.7, 71.2, 65.1, 63.6, 50.0, 40.8, 32.0, 31.3. HRMS (ESI): m/z [M + Na]+ calcd for C13H15NNaO4: 272.0893; found: 272.0894.