Synthesis of Dihydromotuporamine C via 3-Azonia-Cope Rearrangement of 11-Membered Cyclic α-Vinylamine

摘要

A new synthesis of dihydromotuporamine C(dhMotC),a synthetic analogue of cytotoxic marine alkaloid,has been achieved from inexpensive starting materials.The first stage was the preparation of cyclodecanone by sequential [2+2]-cycloaddition of N-(1-cycloocten-1-yl)pyrrolidine with methyl propiolate and electrocyclic ring-opening,followed by basic hydrolysis.Beckmann rearrangement of cyclodecanone oxime and several step manipulations afforded the pivotal intermediate of the N-benzylated 11-membered cyclic α-vinylamine.The final synthesis of dihydromotuporamine C involved tandem nucleophilic addition with ethynyl p-tolyl sulfone and 3-azonia-Cope rearrangement to form the 15-membered aza-macrocycle and reductive amination to install the appended spermidinelike moiety.