Synthesis 2022; 54(07): 1850-1856
DOI: 10.1055/a-1633-8333
paper

Protecting-Group-Free Total Synthesis of Anticancer (±)-Melotenine A

Adisak Thanetchaiyakup
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Hassayaporn Rattanarat
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Sudaporn Aree
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Tanwawan Duangthongyou
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Tanin Nanok
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
Nutthawat Chuanopparat
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
,
a   Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
b   Center of Excellence for Innovation in Chemistry, Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
› Author Affiliations
Financial support was provided by the Thailand Research Fund (DBG5480018) and the Royal Golden Jubilee Advanced Program (RAP61K0005) under the Thailand Research Fund. Additional financial support was provided by the Kasetsart University Research and Development Institute (KURDI), the Center of Excellence for Innovation in Chemistry (PERCH-CIC), the Ministry of Higher Education, Science, Research and Innovation, Thailand, and the Department of Chemistry, Faculty of Science, Kasetsart University.


Abstract

Melotenine A, isolated from Melodinus tenuicaudatus, possesses significant anticancer activity against several human cancer cell lines. The synthesis of (±)-melotenine A was achieved without the use of any protecting groups in 11 steps with an overall yield of 6.7%. The key steps of our strategy were a Diels–Alder reaction to construct the tetracyclic framework and ring-closing metathesis to form the seven-membered ring of (±)-melotenine A.

Supporting Information



Publication History

Received: 06 August 2021

Accepted after revision: 03 September 2021

Accepted Manuscript online:
03 September 2021

Article published online:
12 October 2021

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  • References

  • 1 Feng T, Li Y, Liu Y.-P, Cai X.-H, Wang Y.-Y, Luo X.-D. Org. Lett. 2010; 12: 968
    • 2a Zhao S, Sirasani G, Vaddypally S, Zdilla MJ, Andrade RB. Angew. Chem. Int. Ed. 2013; 52: 8309
    • 2b Zhao S, Sirasani G, Vaddypally S, Zdilla MJ, Andrade RB. Tetrahedron 2016; 72: 6107
  • 3 Du J.-Y, An X.-T, Zhao X.-H, Ma X.-Y, Cao Y.-X, Fan C.-A. Tetrahedron 2019; 75: 1760
    • 4a Kuehne ME, Earley WG. Tetrahedron 1983; 39: 3707
    • 4b Kuehne ME, Bohnert JC, Bornmann WG, Kirkemo CL, Kuehne SE, Seaton PJ, Zebovitz TC. J. Org. Chem. 1985; 50: 919
  • 5 Chen P, Cao L, Li C. J. Org. Chem. 2009; 74: 7533
  • 6 CCDC 2094865 (2a) contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures. See the Supporting Information for details.
    • 7a Compain P. Adv. Synth. Catal. 2007; 349: 1829
    • 7b Wilson GO, Porter KA, Weissman H, White SR, Sottos NR, Moore JS. Adv. Synth. Catal. 2009; 351: 1817
  • 8 Fu GC, Nguyen ST, Grubbs RH. J. Am. Chem. Soc. 1993; 115: 9856
  • 9 Ranaivondrambola T, Hatton W, Felpin F.-X, Evain M, Mathé-Allainmat M, Lebreton J. Synlett 2010; 1631
  • 10 Liu Y.-T, Li L.-P, Xie J.-H, Zhou Q.-L. Angew. Chem. Int. Ed. 2017; 56: 12708
  • 11 Stavber G, Zupan M, Stavber S. Tetrahedron Lett. 2006; 47: 8463
  • 12 Aversa MC, Barattucci A, Bonaccorsi P, Giannetto P. Tetrahedron 2002; 58: 10145
  • 13 Jurissek C, Berger F, Eisenreich F, Kathan M, Hecht S. Angew. Chem. Int. Ed. 2019; 58: 1945
  • 14 Guevel A.-C, Hart DJ. J. Org. Chem. 1996; 61: 465
  • 15 Blencowe PS, Barrett AG. M. Eur. J. Org. Chem. 2014; 4844
  • 16 Sparling BA, Moslin RM, Jamison TF. Org. Lett. 2008; 10: 1291
  • 17 Rollin P, Pougny J.-R. Tetrahedron 1986; 42: 3479
  • 18 Saini G, Mondal A, Kapur M. Org. Lett. 2019; 21: 9071