High-performance liquid chromatographic enantioseparation of intermediates relating to the total synthesis of (−)-physostigmine

Abstract

()-Physostigmine (1) is a clinically useful anticholinesterase agent which has been used in the treatment of myasthenia gravis and glaucoma. More recently, selected ()-physostigmine analogues have also shown promise as Alzheimer’s disease therapeutic agents. Our interests in new (-)-physostigmine analogues have led us to develop a stereoselective synthesis of ()-physostigmine [I] (Fig. 1). To facilitate our synthetic effort and to ensure a high optical purity of the synthetic material, we required analytical high-performance liquid chromatographic (HPLC) enantioseparation of the intermediates as shown in the scheme. We report herein the application of derivatized cellulose-based chiral stationary phase (CSP) to the separation of these intermediates.