A Gram-Scale Laboratory Synthesis of Annonaceous Acetogenin Mimic AA005

AA005（1）,a potent anticancer mimicking molecule of natural Annonaceous acetogenin,features a central C 2 -symmetric triglycol moiety and three stereogenic centers.To support ongoing animal studies,a scalable 10-step synthesis of AA005（1） has been studied,optimized and accomplished in this work,starting from commercially available economic materials ethylene glycol and（R）-epichlorohydrin.A regio-and stereo-controlled BF 3 ·Et 2 O-promoted epoxide opening of（R）-epichlorohydrin with ethylene glycol was investigated,optimized and successfully applied to the scalable preparation of the crucial fragment 6 a with C 2 -symmetry.Further successive epoxide openings elaborated both two side chains and the whole skeleton with proper nucleophiles and electrophiles.Comparison and optimization of the reaction sequences finally led to completion of a new multi-gram synthesis ofAA005（1） with satisfactory enantiomeric and diastereomeric purity.