Download PDF
Synthesis 2021; 53(03): 498-508
DOI: 10.1055/s-0040-1706478
feature

Synthesis of the 26-Membered Core of Thiopeptide Natural Products by Scalable Thiazole-Forming Reactions of Cysteine Derivatives and Nitriles

Trevor C. Johnson
a   Department of Chemistry & Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States
,
Mitchell P. Christy
a   Department of Chemistry & Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093, United States
,
Dionicio Siegel∗
b   Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0934, United States   Email: drsiegel@health.ucsd.edu
› Author AffiliationsWe would like to thank the NIH/NCI Training Grant (T32 CA009523) and UC San Diego for funding this project.
› Further Information
   Permissions and Reprints All articles of this category


Abstract

The increased resistance of bacteria to clinical antibiotics is one of the major dilemmas facing human health and without solutions the problem will grow exponentially worse. Thiopeptide natural products have shown promising antibiotic activities and provide an opportunity for the development of a new class of antibiotics. Attempts to directly translate these compounds into human medicine have been limited due to poor physiochemical properties. The synthesis of the core structure of the 26-membered class of thiopeptide natural products is reported using chemistry that enables the synthesis of large quantities of synthetic intermediates and the common core structure. The use of cysteine/nitrile condensation reactions followed by oxidation to generate thiazoles has been key in enabling large academic scale reactions that in many instances avoided chromatography further aiding in accessing large amounts of key synthetic intermediates.

Key words

thiopeptide - natural product - thiazole - scalable - antibiotic - pharmacophore

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706478.
  • Supporting Information


Publication History

Received: 15 July 2020

Accepted after revision: 31 August 2020

Article published online:
15 October 2020

© 2020. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 https://www.cdc.gov/drugresistance/ (accessed Sept. 29, 2020).
    • 2a Tanaka T, Endo T, Shimazu A, Yoshida R, Suzuki Y. J. Antibiot. 1970; 23: 231
    • 2b Endo T, Yonehara H. J. Antibiot. 1978; 31: 623
      CrossrefPubMed
  • 3 Cundliffe E, Thompson J. J. Gen. Microbiol. 1981; 126: 185
    CrossrefPubMed
  • 4 Haste NM, Thienphrapa W, Tran DN, Loesgen S, Sun P, Nam SJ, Jensen PR, Fenical W, Sakoulas G, Nizet V, Hensler ME. J. Antibiot. 2012; 65: 593
    CrossrefPubMed
  • 5 Benazet F, Cartier M, Florent J, Godard C, Jung G, Lunel J, Mancy D, Pascal C, Renaut J, Tarridec P, Theilleux J, Tissier R, Dubost M, Ninet L. Experientia 1980; 36: 414
    CrossrefPubMed
  • 6 Cromwell GL, Stahly TS, Speer VC, O’Kelly R. J. Anim. Sci. 1984; 59: 1125
    CrossrefPubMed
    • 7a Just-Baringo X, Albericio F, Alvarez M. Marine Drugs 2014; 12: 317
      CrossrefPubMed
    • 7b Bagley MC, Dale JW, Merritt EA, Xiong A. Chem. Rev. 2005; 105: 685
      CrossrefPubMed
    • 7c Hughes RA, Moody CJ. Angew. Chem. Int. Ed. 2007; 46: 7930
      CrossrefPubMed
  • 8 Just-Baringo X, Albericio F, Alvarez M. Angew. Chem. Int. Ed. 2014; 53: 6602
    CrossrefPubMed
  • 9 Donia MS, Cimermancic P, Schulze CJ, Wieland Brown LC, Martin J, Mitreva M, Clardy J, Linington RG, Fischbach MA. Cell 2014; 158: 1402
    CrossrefPubMed
  • 10 Kazami JO. T, Watanabe M, Kamigiri K, Yamaguchi T, Tatsuta K. WO2007049582 A1, 2007
    CrossrefPubMed
    • 11a Acker MG, Bowers AA, Walsh CT. J. Am. Chem. Soc. 2009; 131: 17563
      CrossrefPubMed
    • 11b Bowers AA, Acker MG, Koglin A, Walsh CT. J. Am. Chem. Soc. 2010; 132: 7519
      CrossrefPubMed
    • 11c Li CX, Zhang FF, Kelly WL. Mol. Biosyst. 2011; 7: 82
      CrossrefPubMed
    • 11d Li CX, Zhang FF, Kelly WL. Chem. Commun. 2012; 48: 558
      CrossrefPubMed
  • 12 Bowers AA, Acker MG, Young TS, Walsh CT. J. Am. Chem. Soc. 2012; 134: 10313
    CrossrefPubMed
    • 13a Baumann S, Schoof S, Bolten M, Haering C, Takagi M, Shin-ya K, Arndt HD. J. Am. Chem. Soc. 2010; 132: 6973
      CrossrefPubMed
    • 13b Zhang CW, Occi J, Masurekar P, Barrett JF, Zink DL, Smith S, Onishi R, Ha SH, Salazar O, Genilloud O, Basilio A, Vicente F, Gill C, Hickey EJ, Dorso K, Motyl M, Singh SB. J. Am. Chem. Soc. 2008; 130: 12102
      CrossrefPubMed
    • 13c Singh SB, Zhang CW, Zink DL, Herath K, Ondeyka J, Masurekar P, Jayasuriya H, Goetz MA, Tormo JR, Vicente F, Martin J, Gonzalez I, Genilloud O. J. Antibiot. 2013; 66: 599
      CrossrefPubMed
    • 14a Nicolaou KC, Zak M, Safina BS, Estrada AA, Lee SH, Nevalainen M. J. Am. Chem. Soc. 2005; 127: 11176
      CrossrefPubMed
    • 14b Nicolaou KC, Safina BS, Zak M, Lee SH, Nevalainen M, Bella M, Estrada AA, Funke C, Zecri FJ, Bulat S. J. Am. Chem. Soc. 2005; 127: 11159
      CrossrefPubMed
    • 14c Nicolaou KC, Safina BS, Zak M, Estrada AA, Lee SH. Angew. Chem. Int. Ed. 2004; 43: 5087
      CrossrefPubMed
    • 14d Nicolaou KC, Zak M, Safina BS, Lee SH, Estrada AA. Angew. Chem. Int. Ed. 2004; 43: 5092
      CrossrefPubMed
  • 15 Wojtas KP, Riedrich M, Lu JY, Winter P, Winkler T, Walter S, Arndt HD. Angew. Chem. Int. Ed. 2016; 55: 9772
    CrossrefPubMed
    • 16a Bentley DJ, Fairhurst J, Gallagher PT, Manteuffel AK, Moody CJ, Pinder JL. Org. Biomol. Chem. 2004; 2: 701
      CrossrefPubMed
    • 16b Lu JY, Arndt HD. J. Org. Chem. 2007; 72: 4205
      CrossrefPubMed
    • 16c Lu JY, Riedrich M, Mikyna M, Arndt HD. Angew. Chem. Int. Ed. 2009; 48: 8137
      CrossrefPubMed
    • 16d Lu JY, Riedrich M, Wojtas KP, Arndt HD. Synthesis 2013; 45: 1300
      Article in Thieme Connect
    • 17a Muller HM, Delgado O, Bach T. Angew. Chem. Int. Ed. 2007; 46: 4771
      CrossrefPubMed
    • 17b Lefranc D, Ciufolini MA. Angew. Chem. Int. Ed. 2009; 48: 4198
      CrossrefPubMed
    • 17c Hughes RA, Thompson SP, Alcaraz L, Moody CJ. J. Am. Chem. Soc. 2005; 127: 15644
      CrossrefPubMed
    • 17d Aulakh VS, Ciufolini MA. J. Am. Chem. Soc. 2011; 133: 5900
      CrossrefPubMed
    • 17e Just-Baringo X, Bruno P, Ottesen LK, Canedo LM, Albericio F, Alvarez M. Angew. Chem. Int. Ed. 2013; 52: 7818
      CrossrefPubMed
    • 17f Akasapu S, Hinds AB, Powell WC, Walczak MA. Chem. Sci. 2019; 10: 1971
      CrossrefPubMed
  • 18 Christy MP, Johnson T, McNerlin CD, Woodard J, Nelson AT, Lim B, Hamilton TL, Freiberg KM, Siegel D. Org. Lett. 2020; 22: 2365
    CrossrefPubMed
  • 19 White EH, Field GF, McCapra F. J. Am. Chem. Soc. 1963; 85: 337
    Crossref
  • 20 Martinez V, Davyt D. Tetrahedron: Asymmetry 2013; 24: 1572
    Crossref
  • 21 Robak MT, Herbage MA, Ellman JA. Chem. Rev. 2010; 110: 3600
    CrossrefPubMed
  • 22 Ferreira PT, Maia HS, Monteiro L. J. Chem. Soc., Perkin Trans. 1 1999; 3697
  • 23 Caron S, Do NM, Sieser JE. Tetrahedron Lett. 2000; 41: 2299
    Crossref
  • 24 Kopp F, Wunderlich S, Knochel P. Chem. Commun. 2007; 2075
    PubMed
  • 25 LaMarche MJ, Leeds JA, Amaral A, Brewer JT, Bushell SM, Deng G, Dewhurst JM, Ding J, Dzink-Fox J, Gamber G, Jain A, Lee K, Lee L, Lister T, McKenney D, Mullin S, Osborne C, Palestrant D, Patane MA, Rann EM, Sachdeva M, Shao J, Tiamfook S, Trzasko A, Whitehead L, Yifru A, Yu D, Yan W, Zhu Q. J. Med. Chem. 2012; 55: 2376
    CrossrefPubMed