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 language | English |
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Pages (from-to) | 1327-1337 |
Number of pages | 11 |
Journal | Monatshefte für Chemie - Chemical Monthly |
Volume | 154 |
Issue number | 12 |
Early online date | 19 Oct 2021 |
DOIs | |
Publication status | Published - Dec 2023 |
Keywords
- Cyclization
- Heterocycles
- Indicator dye
- Medicinal chemistry
- Ullman coupling
ASJC Scopus subject areas
- General Chemistry
Fields of Expertise
- Human- & Biotechnology