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Trapped in Misbelief for Almost 40 Years: Selective Synthesis of the Four Stereoisomers of Mefloquine
Author(s) -
Schützenmeister Nina,
Müller Michael,
Reinscheid Uwe M.,
Griesinger Christian,
Leonov Andrei
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201303403
Subject(s) - mefloquine , absolute configuration , enantioselective synthesis , enantiomer , sonogashira coupling , domino , stereochemistry , chemistry , combinatorial chemistry , malaria , organic chemistry , plasmodium falciparum , catalysis , biology , palladium , immunology
Here we report the synthesis of all four stereoisomers of mefloquine. Mefloquine (Lariam) is an important anti‐malaria drug that is applied as a racemate of the erythro form. However, the (−)‐isomer induces psychosis, while the (+)‐enantiomer does not have this undesired side effect. There are six syntheses of which five lead to the wrong enantiomer without the authors of these syntheses noting that they had synthesized the wrong compound. At the same time physical chemistry investigations had assigned the absolute configuration correctly and the last enantioselective synthesis that took these results into account delivered the correct absolute configuration. Since various synthetic approaches failed to provide the correct stereoisomers in previous syntheses, we submit here a synthetic approach with a domino Sonogashira‐6π‐electrocyclisation as key step that confirmed synthetically the correct absolute configuration of all four isomers.