Synthetic studies on (-)-allosamizoline

Abstract

Allosamidin exhibits inhibitory activity against chitinases. It has been thought that the chitinases inhibitor would be a good model for insect growth regulators. Allosamidin consists of 2 equivalents of N-acetyl-D-allosamine and 1 equivalent of a new aminocyclitol, named (-)-allosamizoline. For the synthesis of (-)-allosamizoline, two independent routes were attempted. In our first approach, synthesis of the key intermediate, hydroxymethyl-2-cyclopentene 41 was unsuccessful. In our second approach, cyclopentane 45 was chosen as a crucial intermediate, which could be formed via an intramolecular radical cyclization of phenyl selenoester. Prior to the main event to synthesize 45, we carried out a model study using D-glucose. Radical cyclization of phenyl selenoester 109 was employed as a key step. Treatment of 109 with tri-n-butyltinhydride in the presence of AIBN furnished a 10:1 mixture of cyclopentanes 110 and 111 in 60% yield. From the model study we ascertained that the radical cyclization of phenyl selenoester 124 would be applied successfully to the synthesis of (-)-allosamizoline.