On the resolution of fenfluramine

Area of Science:

• Chiral chemistry
• Pharmaceutical analysis

Background:

• Fenfluramine is a chiral compound with distinct enantiomers.
• Accurate enantiomeric resolution is crucial for pharmaceutical applications.

Purpose of the Study:

• To clarify the correct enantiomer of fenfluramine obtained using (+)-dibenzoyltartaric acid.
• To establish an optimal method for resolving both fenfluramine enantiomers.

Main Methods:

• Chiral resolution using dibenzoyltartaric acid enantiomers.
• Characterization of intermediate dibenzoyltartrate salts.
• Confirmation of absolute configurations.

Main Results:

• Resolution with (+)-dibenzoyltartaric acid yields (+)-fenfluramine, contrary to previous reports.
• The absolute configurations of fenfluramine enantiomers were confirmed.
• A sequential resolution method using both (-)- and (+)-dibenzoyltartaric acid is proposed.

Conclusions:

• The established literature on fenfluramine enantiomer resolution requires correction.
• A preferred sequential method facilitates the isolation of both fenfluramine enantiomers.
• Precise enantiomeric separation is vital for understanding drug properties.