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Biomimetic Total Synthesis of Mbandakamine A and Further Antiplasmodial Naphthylisoquinoline Dimers
Author(s) -
Schies Christine,
Seupel Raina,
Feineis Doris,
Gehrold Andreas,
Schraut Michaela,
Kaiser Marcel,
Brun Reto,
Bringmann Gerhard
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201703160
Subject(s) - monomer , demethylation , atropisomer , total synthesis , phenol , stereochemistry , chemistry , alkaloid , oxidative coupling of methane , steric effects , biomimetic synthesis , organic chemistry , polymer , biochemistry , gene expression , methane , dna methylation , gene
The first total synthesis of mbandakamine A, an unsymmetrically coupled dimeric naphthylisoquinoline alkaloid with a high steric hindrance, is described. Key step was the phenol‐oxidative cross‐coupling of its two 5,8’‐linked monomeric units, 5‐ epi ‐korupensamine E and 8‐ O ‐methylkorupensamine A. These two naphthylisoquinolines were synthesized atroposelectively by applying the ′lactone method′. As an alternative to the largely separate synthesis of the two monomers, both of them were provided simultaneously, by the – intentionally non‐selective – O ‐demethylation of a late joint precursor, thus shortening the synthesis substantially. Oxidative coupling of a 1:1 mixture of the two monomers provided mbandakamine A as a single atropisomer, along with four further naphthylisoquinoline dimers, nearly all of them based on new coupling types. Some of these new quateraryls showed excellent antiplasmodial activities, in particular the 6’‐6’’‐coupled main product.