Qun K. Fang

Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

Abstract A stereospecific method for the synthesis of enantiopure α-aminoketone from its corresponding α-hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite.

First preparation of enantiomerically pure sibutramine and its major metabolite, and determination of their absolute configuration by single crystal X-ray analysis

Abstract Racemic sibutramine was resolved with dibenzoyl- d -tartaric acid, and the absolute stereochemistry of sibutramine was determined by single crystal X-ray crystallography of its dibenzoyl d -tartrate. The major active metabolite (desmethylsibutramine) was obtained by demethylation of sibutramine with DEAD. Enantiomeric purity of sibutramine was determined by HPLC on an Ultron ES-OVM column.

An efficient and facile synthesis of racemic and optically active fexofenadine

Abstract An efficient and practical method for the synthesis of racemic and optically active (96% ee) fexofenadine is described. The key racemic or optically active lactol intermediate 2 is prepared from readily available tolyl derivative 3 .

First practical synthesis of enantiomerically pure (R)- and (S)-desmethylsibutramine (DMS) and unambiguous determination of their absolute configuration by single-crystal X-ray analysis

A practical synthesis of enantiomerically pure (R)-desmethylsibutramine [(R)-DMS] and (S)-desmethylsibutramine [(S)-DMS] is outlined along with an improved synthesis of racemic desmethylsibutramine. This route was used for kilo-scale production of enantiomerically pure (R)- and (S)-DMS. Racemic desmethylsibutramine was resolved with either (R)- or (S)-mandelic acid, and the absolute stereochemistry of DMS was determined by single X-ray crystallography of its mandelate salt.

Synthesis of enantiomerically pure desmethylzopiclone and determination of its absolute configuration

Abstract Two synthetic methods have been established for the preparation of enantiomerically pure desmethylzopiclone, a metabolite of zopiclone. In Method A, (S)-desmethylzopiclone was prepared by demethylation of (S)-zopiclone with 1-chloroethyl chloroformate in high yield. Enantiomerically pure zopiclone (>99% ee) was obtained through a highly efficient resolution process in >36% overall yield. In Method B, racemic desmethylzopiclone was resolved with l -N-benzyloxycarbonyl phenylalanine ( l -ZPA) followed by recrystallization in good yield. The absolute stereochemistry of the (+)-enantiomer was first determined to be the (S)-configuration by X-ray crystallography.