Total synthesis of 1-Deoxy-6,7,8a-epi-Castanospermine, (+)-Epiquinamide, (+)-CP-99,994 and Orthogonal N-Deacetylation and N-Cbz Deprotection

Abstract

Total syntheses of 1-deoxy-7,8a-di- epi -Castanospermine, (+)-Epiquinamide and formal synthesis of Pumiliotoxin 251D have been achieved using novel strategies in minimal number of steps starting from naturally occurring enantiopure alpha-amino acids. W e have also developed a highly efficient and useful approach for constructing cis -2- aryl 3-amino piperidines with an option of introducing diverse aryl groups at C-2 position. This gives an easy access to condense different aldehydes at C-3 amine functionality without compromising the stereochemistry. This novel method opens a wide and easy access to synthesize variety of cis -2- aryl 3-amino piperidines in general and in particular synthesis of various congeners of (+)-CP-99,994 to test their biological activity against NK-1-Substance P receptor. Some of the difficulties faced during the total syntheses led to the development of novel methods for orthogonal N -deacetylation and N -Cbz deprotection. These deprotection methods have been systematically studied under mild reaction conditions.