Synthesis of diastereomeric 13-amido-substituted huprines as potential high affinity acetylcholinesterase inhibitors

Abstract

Two diastereomeric huprines additionally functionalized at position 13 with a methanesulfonamido group have been synthesized in seven steps from the known 9,9-ethylenedioxybicyclo[3.3.1]nonane-3,7-dione ( 5 ). In a key-step, nickel boride non-stereoselective reduction of an oxime gave a mixture of amines which was separated as methanesulfonamido derivatives. The substitution pattern of these huprines could lead to an extended binding near the active site of acetylcholinesterase (AChE), and consequently to improved AChE inhibitors.