Total Synthesis of GE81112A: An Orthoester-Based Approach

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Autoren

  • Scherin Fayad
  • Ardalan Jafari
  • Sören M.M. Schuler
  • Michael Kurz
  • Oliver Plettenburg
  • Peter E. Hammann
  • Armin Bauer
  • Gerrit Jürjens
  • Christoph Pöverlein

Externe Organisationen

  • Sanofi-Aventis Deutschland GmbH
  • Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
  • Fraunhofer-Institut Molekularbiologie und Angewandte Oekologie IME
  • Evotec International GmbH
Forschungs-netzwerk anzeigen

Details

OriginalspracheEnglisch
Seiten (von - bis)5597-5608
Seitenumfang12
FachzeitschriftJournal of Organic Chemistry
Jahrgang88
Ausgabenummer9
Frühes Online-Datum6 Apr. 2023
PublikationsstatusVeröffentlicht - 5 Mai 2023
Extern publiziertJa

Abstract

The GE81112 series, consisting of three naturally occurring tetrapeptides and synthetic derivatives, is evaluated as a potential lead structure for the development of a new antibacterial drug. Although the first total synthesis of GE81112A reported by our group provided sufficient amounts of material for an initial in depth biological profiling of the compound, improvements of the routes toward the key building blocks were needed for further upscaling and structure-activity relationship studies. The major challenges identified were poor stereoselectivity in the synthesis of the C-terminal β-hydroxy histidine intermediate and a concise access to all four isomers of the 3-hydroxy pipecolic acid. Herein, we report a second-generation synthesis of GE81112A, which is also applicable to access further representatives of this series. Based on Lajoie’s ortho-ester-protected serine aldehydes as key building blocks, the described route provides both a satisfactory improvement in stereoselectivity of the β-hydroxy histidine intermediate synthesis and a stereoselective approach toward both orthogonally protected cis and trans-3-hydroxy pipecolic acid.

ASJC Scopus Sachgebiete

Zitieren

Total Synthesis of GE81112A: An Orthoester-Based Approach. / Fayad, Scherin; Jafari, Ardalan; Schuler, Sören M.M. et al.
in: Journal of Organic Chemistry, Jahrgang 88, Nr. 9, 05.05.2023, S. 5597-5608.

Publikation: Beitrag in FachzeitschriftArtikelForschungPeer-Review

Fayad, S, Jafari, A, Schuler, SMM, Kurz, M, Plettenburg, O, Hammann, PE, Bauer, A, Jürjens, G & Pöverlein, C 2023, 'Total Synthesis of GE81112A: An Orthoester-Based Approach', Journal of Organic Chemistry, Jg. 88, Nr. 9, S. 5597-5608. https://doi.org/10.1021/acs.joc.3c00094
Fayad, S., Jafari, A., Schuler, S. M. M., Kurz, M., Plettenburg, O., Hammann, P. E., Bauer, A., Jürjens, G., & Pöverlein, C. (2023). Total Synthesis of GE81112A: An Orthoester-Based Approach. Journal of Organic Chemistry, 88(9), 5597-5608. https://doi.org/10.1021/acs.joc.3c00094
Fayad S, Jafari A, Schuler SMM, Kurz M, Plettenburg O, Hammann PE et al. Total Synthesis of GE81112A: An Orthoester-Based Approach. Journal of Organic Chemistry. 2023 Mai 5;88(9):5597-5608. Epub 2023 Apr 6. doi: 10.1021/acs.joc.3c00094
Fayad, Scherin ; Jafari, Ardalan ; Schuler, Sören M.M. et al. / Total Synthesis of GE81112A : An Orthoester-Based Approach. in: Journal of Organic Chemistry. 2023 ; Jahrgang 88, Nr. 9. S. 5597-5608.
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title = "Total Synthesis of GE81112A: An Orthoester-Based Approach",
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T2 - An Orthoester-Based Approach

AU - Fayad, Scherin

AU - Jafari, Ardalan

AU - Schuler, Sören M.M.

AU - Kurz, Michael

AU - Plettenburg, Oliver

AU - Hammann, Peter E.

AU - Bauer, Armin

AU - Jürjens, Gerrit

AU - Pöverlein, Christoph

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PY - 2023/5/5

Y1 - 2023/5/5

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