Total synthesis of the isoquinolinium metabolite ETM-204 of Trabectidin

被引：3

作者：

Lembacher-Fadum, Christian ^{[1
]}

Gissing, Simon ^{[1
]}

Pour, Georg ^{[2
]}

Breinbauer, Rolf ^{[1
]}

机构：

[1] Graz Univ Technol, Inst Organ Chem, Graz, Austria

[2] Ever Valinject GmbH, Unterach Am Attersee, Austria

来源：

MONATSHEFTE FUR CHEMIE | 2023年 / 154卷 / 12期

关键词：

Cyclization; Heterocycles; Indicator dye; Medicinal chemistry; Ullman coupling; IN-VITRO; ET-743; YONDELIS(R);

D O I：

10.1007/s00706-021-02844-1

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Ecteinascidin-743 (Trabectidin, Trabectedin(R), Yondelis(R)) 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 Skattebol-formylation, and a modified Pomeranz-Fritsch cyclization to assemble the isoquinoline ring. The pH-dependence of its visual absorbance could be clarified. [GRAPHICS] .

引用

页码：1327 / 1337

页数：11

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