Synthesis and characterization of (-)Galanthamine hydrobromide and memantine hydrochloride as anti Alzheimers drugs and their impurities

Abstract

Chapter-I deals with the introduction to Alzheimer?s disease, biological importance of (-)-Galanthamine, Memantine and the previous synthetic approaches cited in the literature towards the synthesis of racemic.Galanthamine 1. In chapter-II, studies towards the total synthesis of (-) Galanthamine and its hydro bromide salt is described, wherein a stereo selective reduction of prochiral ketone using L-selectride followed by diastereomeric separation using di-p-toluyl-D-tartaric acid. Synthesis and characterization of Galanthamine process related chiral impurities have been described in chapter-III. A detailed study on polymorphism of Galanthamine amorphous and crystalline forms is presented in chapter-IV. An improved, cost effective and scalable process has been developed for Memantine hydrochloride. CHAPTER-I This chapter deals with the introduction to Alzheimer?s disease, biological importance of (-)-Galanthamine and the previous synthetic approaches cited in the literature towards the synthesis of racemic and (-) Galanthamine 1. CHAPTER-II This chapter describes the studies towards the total synthesis of (-) Galanthamine and its hydrobromide salt, through a stereo selective reduction of prochiral ketone using L-selectride followed by diasteromeric separation using p-diparatoluyl-D-tartaric acid. CHAPTER- III Synthesis and characterization of Galanthamine process related chiral impurities have been described in chapter-III. Impurities are in pharmaceutical industry are the unwanted chemicals that remain with the active pharmaceutical ingredients (API?s) or developed during synthesis of API or in formulation. Various regulatory authorities like ICH, USFDA, Canadian Drug and Health agency are emphasizing on the purity requirements and the identification of impurities in API?s. Formation of impurities due to incomplete chemical reactions, Impurities originating from impurities in the starting material of the synthesis.