Synthesis and evaluation of oxime derivatives as modulators for amyloid beta-induced mitochondrial dysfunction.

Starting from quinuclidinyl oxime 1 identified by preliminary screening, a series of azacycles-containing oxime derivatives was synthesized. Their mPTP blocking activities were evaluated by a JC-1 assay, measuring the change of mitochondrial membrane potential. The inhibitory activity of nine compounds against amyloid beta-induced mPTP opening was comparable or even superior to that of piracetam.

Synthesis of 3,4-dimethylidene oxacycles through Prins-type cyclization of allenylmethylsilanes.

An efficient synthesis of 3,4-dimethylidene oxacycles including oxolanes and oxepanes through Prins-type cyclization of hydroxy(allenylmethyl)silanes is described. We have shown that 2-substituted tetrahydrofuran derivatives could be produced by using this strategy although the 5-endo-trig cyclization mode is stereoelectronically disfavored. We also applied our method to the stereoselective synthesis of 2,7-cis-3,4-dimethylidene oxepanes, which were used for constructing more complex ring systems, such as polyether bicycles or tricycles.