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Synthesis
DOI: 10.1055/s-0043-1774861
paper

Syntheses of 7a-Substituted Pyrrolizidine Derivatives via Stereocontrolled Anionic Cyclization

Hongjun Ming
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Darong He
b   Nature Pharmaceutical (Anhui) Co., Ltd, 4th Floor, 6# Building, 8# Huangguan Road, Anqing Hi-Tech Development District, Anqing, Anhui Province, P. R. of China
,
Shengmeng Si
b   Nature Pharmaceutical (Anhui) Co., Ltd, 4th Floor, 6# Building, 8# Huangguan Road, Anqing Hi-Tech Development District, Anqing, Anhui Province, P. R. of China
,
Chao Xu
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Yunge Yuan
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Xiaoran Tian
b   Nature Pharmaceutical (Anhui) Co., Ltd, 4th Floor, 6# Building, 8# Huangguan Road, Anqing Hi-Tech Development District, Anqing, Anhui Province, P. R. of China
,
Zhigang Hu
b   Nature Pharmaceutical (Anhui) Co., Ltd, 4th Floor, 6# Building, 8# Huangguan Road, Anqing Hi-Tech Development District, Anqing, Anhui Province, P. R. of China
,
Shikuo Li
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Hui Zhang
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Fangzhi Huang∗
a   School of Chemistry & Chemical Engineering, Anhui University, Hefei, Anhui Province, 230601, P. R. of China
,
Yue-Lei Chen∗
b   Nature Pharmaceutical (Anhui) Co., Ltd, 4th Floor, 6# Building, 8# Huangguan Road, Anqing Hi-Tech Development District, Anqing, Anhui Province, P. R. of China
› Author AffiliationsThis work is supported by the National Natural Science Foundation of China (Grant Nos. 52172174, 51872002, and 21771001), the Key Research­ and Development Projects in Anhui Province (202004a07020026), and the Program of Anhui Scientific and Technical Leaders Reserve Candidates (2018RH168).
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Dedicated to Prof. Dr. Jun-Da Cen on the occasion of his 60th birthday.

Abstract

Starting from inexpensive proline and epichlorohydrin, a pivotal stereocontrolled anionic cyclization reaction paves the way for a robust and adaptable methodology to produce stereoisomers of 7a-substituted pyrrolizidine derivatives. This process yields intriguing 7a-hydroxymethyl pyrrolizidine derivatives, among them valuable trans-(2-fluorohexahydro-1H-pyrrolizin-7a-yl)methanol, which is attainable through multiple steps.

Key words

pyrrolizidine alkaloids - 7a-substituted pyrrolizidine - stereocontrolled synthesis - anionic cyclization - total synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1774861.
  • Supporting Information


Publication History

Received: 02 February 2024

Accepted after revision: 15 April 2024

Article published online:
06 May 2024

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  • References

  • 1 Moreira R, Pereira DM, Valentão P, Andrade PB. Int. J. Mol. Sci. 2018; 19: 1668
    CrossrefPubMed
  • 2 Robertson J, Stevens K. Nat. Prod. Rep. 2017; 34: 62
    CrossrefPubMed
  • 3 Schramm S, Köhler N, Rozhon W. Molecules 2019; 24: 498
    CrossrefPubMed
  • 4 Evans DeWald L, Starr C, Butters T, Treston A, Warfield KL. Antiviral Res. 2020; 184: 104881
    CrossrefPubMed
  • 5 Horne G. Iminosugars: Therapeutic Applications and Synthetic Considerations . In Carbohydrates as Drugs . Seeberger PH, Rademacher C. Topics in Medicinal Chemistry 12; Springer International Publishing; Cham: 2014: 23-51
    CrossrefGoogle Scholar
  • 6 Horne G, Wilson FX, Tinsley J, Williams DH, Storer R. Drug Discovery Today 2011; 16: 107
    CrossrefPubMed
  • 7 Martin O. Ann. Pharm. Fr. 2007; 65: 5
    CrossrefPubMed
  • 8 Nash RJ, Kato A, Yu C.-Y, Fleet GW. Future Med. Chem. 2011; 3: 1513
    CrossrefPubMed
  • 9 Wei X, Ruan W, Vrieling K. Molecules 2021; 26: 1970
    CrossrefPubMed
  • 10 Chen Y.-L, Leguijt R, Redlich H. Synthesis 2006; 2242
  • 11 Chen Y.-L, Redlich H, Bergander K, Fröhlich R. Org. Biomol. Chem. 2007; 5: 3330
    CrossrefPubMed
  • 12 Ratmanova NK, Andreev IA, Leontiev AV, Momotova D, Novoselov AM, Ivanova OA, Trushkov IV. Tetrahedron 2020; 76: 131031
    CrossrefPubMed
  • 13 Wang H, Chi L, Yu F, Dai H, Gao C, Si X, Wang Z, Liu L, Zheng J, Shan L, Liu H, Zhang Q. Eur. J. Med. Chem. 2023; 249: 115124
    CrossrefPubMed
  • 14 Wang X, Allen S, Blake JF, Bowcut V, Briere DM, Calinisan A, Dahlke JR, Fell JB, Fischer JP, Gunn RJ, Hallin J, Laguer J, Lawson JD, Medwid J, Newhouse B, Nguyen P, O’Leary JM, Olson P, Pajk S, Rahbaek L, Rodriguez M, Smith CR, Tang TP, Thomas NC, Vanderpool D, Vigers GP, Christensen JG, Marx MA. J. Med. Chem. 2022; 65: 3123
    CrossrefPubMed
  • 15 Li D, Layton ME, Roecker AJ, Egbertson M, Jones KL. G, Wang X, Peng X. (Merck Sharp & Dohme Corp.) WO2015080988A1, 2015
    PubMed
  • 16 Wang X, Burns AC, Christensen JG, Ketcham JM, Lawson JD, Marx MA, Smith CR, Allen S, Blake JF, Chicarelli MJ, Dahlke JR, Dai D, Fell JB, Fischer JP, Mejia MJ, Newhouse B, Nguyen P, O’Leary JM, Pajk S, Rodriguez ME, Savechenkov P, Tang TP, Vigers GP. A, Zhao Q. (Mirati Therapeutics INC, Array Biopharma INC) WO2021041671A1, 2021
    PubMed
  • 17 Burns NZ, Baran PS, Hoffmann RW. Angew. Chem. Int. Ed. 2009; 48: 2854
    CrossrefPubMed
  • 18 Guo W, Gharbaoui T, Lizza JR, Meng F, Wang Y, Xin M, Chen Y, Li J, Chen C.-Y. Org. Process Res. Dev. 2022; 26: 2839
    Crossref
  • 19 Seebach D, Sting AR, Hoffmann M. Angew. Chem. Int. Ed. 1996; 35: 2708
    Crossref