Download PDF
Synthesis 2023; 55(13): 1961-1983
DOI: 10.1055/a-2013-9333
feature

New Demethylated Derivatives of Carolacton and Structure–Activity Relationship (SAR) Studies on Their Biofilm Inhibitory Properties

Jonas Ammermann
a   Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany
,
Janina Meyer
a   Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany
,
Jannik Donner
b   Helmholtz Centre for Infection Research, Department of Microbial Communication, Inhoffenstr. 7, 38124 Braunschweig, Germany
,
Michael Reck
b   Helmholtz Centre for Infection Research, Department of Microbial Communication, Inhoffenstr. 7, 38124 Braunschweig, Germany
,
Irene Wagner-Döbler
b   Helmholtz Centre for Infection Research, Department of Microbial Communication, Inhoffenstr. 7, 38124 Braunschweig, Germany
,
Andreas Kirschning  ∗
a   Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany
› Author AffiliationsThis work has been carried out as an integral part of the Biofabrication for NIFE Initiative, which is financially supported by the Niedersächsisches Ministerium für Wissenschaft und Kultur (MWK, Lower Saxony Ministry of Science and Culture) and the Volkswagen Foundation.
› Further Information
    Permissions and Reprints All articles of this category


Abstract

The total synthesis of a series of new carolacton derivatives that mainly lack selected methyl substituents along the polyketide backbone is reported. Their inhibitory activity towards bacterial biofilms revealed that selective removal of the methyl group at C10 does not have a major effect on biological activity, whereas additional removal of the methyl group at C14 in carolacton results in a large decrease in antibacterial activity. A key new feature of this work is the replacement of the Nozaki–Hiyama–Kishi (NHK) vinylation with a titanium-mediated protocol for the fusion of the two main fragments.

Key words

antibiotics - biofilms - carolacton - Nozaki–Hiyama–Kishi reaction - polyketides - structure–activity relationship studies - total synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2013-9333.
  • Supporting Information


Publication History

Received: 10 December 2022

Accepted after revision: 16 January 2023

Accepted Manuscript online:
16 January 2023

Article published online:
24 March 2023

© 2023. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Jansen R, Irschik H, Huch V, Schummer D, Steinmetz H, Bock M, Schmidt T, Kirschning A, Müller R. Eur. J. Org. Chem. 2010; 1284
    Crossref
  • 2 Kunze B, Reck M, Dötsch A, Lemme A, Schummer D, Irschik H, Steinmetz H, Wagner-Döbler I. BMC Microbiol. 2010; 10: 199
    CrossrefPubMed
    • 3a Reck M, Rutz K, Kunze B, Tomasch J, Surapaneni SK, Schulz S, Wagner-Döbler I. J. Bacteriol. 2011; 193: 5692
      CrossrefPubMed
    • 3b Apel C, Barg A, Rheinberg A, Conrads G, Wagner-Döbler I. Dent. Mater. 2013; 29: 1188
      CrossrefPubMed
    • 3c Donner J, Reck M, Bunk B, Jarek M, App C, Meier-Kolthoff J, Overmann J, Müller R, Kirschning A, Wagner-Döbler I. mSphere 2017; 2: e00375-17
      CrossrefPubMed
  • 4 Donner J, Reck M, Bergmann S, Kirschning A, Müller R, Wagner-Döbler I. Sci. Rep. 2016; 6: 29677
    CrossrefPubMed
    • 5a Schmidt T, Kirschning A. Angew. Chem. Int. Ed. 2012; 51: 1063
      CrossrefPubMed
    • 5b Hallside MS, Brzozowski RS, Wuest WM, Phillips AJ. Org. Lett. 2014; 16: 1148
      CrossrefPubMed
    • 5c Kuilya TK, Goswami RK. Org. Lett. 2017; 19: 2366
      CrossrefPubMed
  • 6 Stumpp N, Premnath P, Schmidt T, Ammermann J, Dräger G, Reck M, Jansen R, Stiesch M, Wagner-Döbler I, Kirschning A. Org. Biomol. Chem. 2015; 13: 5765
    CrossrefPubMed
  • 7 Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim S.-H, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FY. F, Long BH, Vite GD. J. Am. Chem. Soc. 2000; 122: 8890
    CrossrefPubMed
  • 8 Hügel HM, Smith AT, Rizzacasa MA. Org. Biomol. Chem. 2016; 14: 11301
    CrossrefPubMed
  • 9 Ammermann J, Schmidt T, Donner J, Reck M, Wagner-Döbler I, Kirschning A. Org. Biomol. Chem. 2017; 15: 8553
    CrossrefPubMed
  • 10 Solinski AE, Koval AB, Brzozowski RS, Morrison KR, Fraboni AJ, Carson CE, Eshraghi AR, Zhou G, Quivey RG, Voelz VA, Buttaro BA, Wuest WM. J. Am. Chem. Soc. 2017; 139: 7188
    CrossrefPubMed
  • 11 Fu C, Sikandar A, Donner J, Zaburannyi N, Herrmann J, Reck M, Wagner-Döbler I, Koehnke J, Müller R. Nat. Commun. 2017; 8: 1529
    CrossrefPubMed
  • 12 Zhou J, Fu GC. J. Am. Chem. Soc. 2003; 125: 14726
    CrossrefPubMed
  • 13 Geist E, Kirschning A, Schmidt T. Nat. Prod. Rep. 2014; 31: 441
    CrossrefPubMed
  • 14 Ley SV, Diez E, Dixon DJ, Guy RT, Michel P, Nattrass GL, Sheppard TD. Org. Biomol. Chem. 2004; 2: 3608
    CrossrefPubMed
    • 15a Gribble G, Joyner HH, Switzer FL. Synth. Commun. 1992; 22: 2997
      Crossref
    • 15b Coleman RS, Lu X, Modolo I. J. Am. Chem. Soc. 2007; 129: 3826
      CrossrefPubMed
  • 16 Review: Marshall JA. J. Org. Chem. 2007; 72: 8153
    CrossrefPubMed
  • 18 Takano S, Akiyama M, Sato S, Ogasawara K. Chem. Lett. 1983; 1593
    CrossrefPubMed
  • 19 Duthaler RO, Herold P, Wyler-Helfer S, Riediker M. Helv. Chim. Acta 1990; 73: 659
    CrossrefPubMed
  • 20 Duthaler RO, Herold P, Lottenbach W, Oertle K, Riediker M. Angew. Chem. Int. Ed. Engl. 1989; 28: 495
    CrossrefPubMed
  • 21 Holmquist CR, Roskamp EJ. J. Org. Chem. 1989; 54: 3258
    CrossrefPubMed
  • 22 Corey EJ, Bakshi RK, Shibata S. J. Am. Chem. Soc. 1987; 109: 5551
    CrossrefPubMed
  • 23 Paterson I, Findlay AD, Florence GJ. Org. Lett. 2006; 8: 2131
    CrossrefPubMed
  • 24 Paterson I, Goodman JM, Isaka M. Tetrahedron Lett. 1989; 30: 7121
    Crossref
  • 25 Evans DA, Chapman KT, Carreira EM. J. Am. Chem. Soc. 1988; 110: 3560
    CrossrefPubMed
  • 26 Li P, Li J, Arikan F, Ahlbrecht W, Dieckmann M, Menche D. J. Org. Chem. 2010; 75: 2429
    CrossrefPubMed
  • 27 Pietruszka J, Witt A. Synthesis 2006; 4266
    Article in Thieme Connect
    • 28a Okude Y, Hirano S, Hiyama T, Nozaki H. J. Am. Chem. Soc. 1977; 99: 3179
      Crossref
    • 28b Hiyama T, Okude Y, Kimura K, Nozaki H. Bull. Chem. Soc. Jpn. 1982; 55: 561
      Crossref
  • 29 Tian Q, Zhang G. Synthesis 2016; 48: 4038
    Article in Thieme ConnectPubMed
  • 30 Kobayashi K, Fujii Y, Hayakawa I, Kigoshi H. Org. Lett. 2011; 13: 900
    CrossrefPubMed
    • 31a Wan Z.-K, Choi H.-W, Kang F.-A, Nakajima K, Demeke D, Kishi Y. Org. Lett. 2002; 4: 4431
      CrossrefPubMed
    • 31b Choi H.-W, Nakajima K, Demeke D, Kang F.-A, Jun H.-S, Wan Z.-K, Kishi Y. Org. Lett. 2002; 4: 4435
      CrossrefPubMed
  • 32 Bahadoor AB, Micalizio G. Org. Lett. 2006; 8: 1181
    CrossrefPubMed
  • 33 Hoye TR, Jeffrey CS, Shao F. Nat. Protoc. 2007; 2: 2451
    CrossrefPubMed
  • 34 Shiina I, Kubota M, Oshiumi H, Hashizume M. J. Org. Chem. 2004; 69: 1822
    CrossrefPubMed
  • 35 Inanga J, Hirata K, Saeki H, Katsuki T, Yamaguchi M. Bull. Chem. Soc. Jpn. 1979; 52: 1989
    CrossrefPubMed
    • 36a Boulos L, Prévost M, Barbeau B, Coallier J, Desjardins R. J. Microbiol. Methods 1999; 37: 77
      CrossrefPubMed
    • 36b Berney M, Hammes F, Bosshard F, Weilenmann H.-U, Egli T. Appl. Environ. Microbiol. 2007; 73: 3283
      CrossrefPubMed
  • 37 Ammermann J. Ph.D. Thesis. Leibniz Universität; Hannover/Germany: 2017
    CrossrefGoogle Scholar
    • 38a Velvadapu V, Glassford I, Lee M, Paul T, DeBrosse C, Klepacki D, Small MC, MacKerell AD. Jr, Andrade RB. ACS Med. Chem. Lett. 2012; 3: 211
      CrossrefPubMed
    • 38b Wagh B, Paul T, DeBrosse C, Klepacki D, Small MC, MacKerell AD. Jr, Andrade RB. ACS Med. Chem. Lett. 2013; 4: 1114
      CrossrefPubMed