The Absolute Configuration of (+)‐ and (−)‐erythro‐Mefloquine

Abstract

The controversy over the absolute configuration of (+)‐erythro‐mefloquine, the less psychosis‐causing enantiomer of the anti‐malarial drug Lariam, has been resolved by Mosher ester crystallization. The configuration determined previously by physical methods (see scheme) is correct, whereas the configuration determined by three enantioselective syntheses is wrong.

Absolute Configuration and Antimalarial Activity of erythro‐Mefloquine Enantiomers

“…While this article was under peer review a related study by Griesinger and co-workers appeared. [9] The authors determined the crystal structures of two MQ enantiomeric Mosher amides.…”

General Quantum-Based NMR Method for the Assignment of Absolute Configuration by Single or Double Derivatization: Scope and Limitations

“…22e,f To terminate this puzzling situation, Reinscheid, Dittrich, Griesinger, and co-workers determined the (11S,12R) configuration for the (+)-isomer by X-ray analysis of the resulting MTPA amides of the two enantiomers of erythro-mefloquine. 23 A few months later, Sonnet and co-workers arrived at the same conclusion by X-ray crystallography, CD spectroscopy, and molecular modeling, 22g and their results were further validated by three total syntheses published the same year. 22h−j To understand how our methodology could have been useful to settle this 40-year controversy, we computed the NMR shifts of the two (R)-and (S)-MTPA amides of (11S,12R)-erythro-mefloquine (compounds 97 and 98, Figure 3).…”

Direkt zur Absolutkonfiguration

“…Auch heute noch ist die Entwicklung neuer Techniken zur Differenzierung und Zuordnung von Enantiomeren Gegenstand der Forschung 11,12. Allen beschriebenen Methoden war jedoch bisher gemein, dass sie das Molekül entweder nur indirekt abbilden und/oder theoretische Annahmen erfordern.…”