The power of complex natural products derived from natural product synthesis

Abstract

Palau’amine has received a great deal of attention as an attractive synthetic target by virtue of its intriguing molecular architecture and significant immunosuppressive activity. Here we report the total synthesis of palau’amine characterized by a Hg(OTf)₂-catalyzed construction of the tetra-substituted carbon center at the C16 position, and the construction of the ABDE tetracyclic ring core including a trans-azabicyclo [3.3.0] octane skeleton. The ABDE tetracyclic ring core is constructed by a cascade reaction initiated by base-induced elimination to form an imine with concomitant N-N bond cleavage, followed by the addition of amide anion to that imine (D-ring formation), and the condensation of a pyrrole unit with a methyl ester (B-ring formation) in a single step. The present synthetic route has the potential to help elucidate the pharmacophore of this natural product, as well as the mechanistic details of its immunosuppressive activity.