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 spermidine-like moiety. © 2020 Wiley-VCH GmbH