Total synthesis of the isoquinolinium metabolite ETM-204 of Trabectidin

Christian Lembacher-Fadum, Simon Gissing, Georg Pour, Rolf Breinbauer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Ecteinascidin-743 (Trabectidin, Trabectedin ®, Yondelis ®) is a synthetically obtained pharmaceutical drug originally isolated from a marine tunicate. Trabectedin is used for the chemotherapy of soft-tissue sarcoma and ovarian cancer. The isoquinolinium metabolite ETM-204 has been found in biotransformation and degradation studies of Trabectedin. We report the first total synthesis of ETM-204 and its full spectroscopic characterization confirming the postulated structure. Central elements of the 12-step synthesis starting from 2-methyl-6-nitrophenol are a Cu-mediated conversion of an iodoarene to a phenol, a Skattebøl-formylation, and a modified Pomeranz–Fritsch cyclization to assemble the isoquinoline ring. The pH-dependence of its visual absorbance could be clarified. Graphic abstract: [Figure not available: see fulltext.]

Original languageEnglish
Number of pages11
JournalMonatshefte für Chemie - Chemical Monthly
DOIs
Publication statusE-pub ahead of print - 2021

Keywords

  • Cyclization
  • Heterocycles
  • Indicator dye
  • Medicinal chemistry
  • Ullman coupling

ASJC Scopus subject areas

  • Chemistry(all)

Fields of Expertise

  • Human- & Biotechnology

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