Efficient methods have been developed for synthesizing hither to unknown macrodiolides incorporating 1Z,5Z-diene and 1,3-diyne moieties in 55-79% yields and with >98% stereoselectivity by intermolecular cyclocondesation of (7Z,11Z)-octadeca-7,11-dienedioic acid with α,ω-diols catalyzed by hafnium triflate Hf(OTf)4, as well as by oxidative coupling of α,ω-diynes obtained by esterification of (7Z,11Z)-octadeca-7,11-dienedioic acid with alkynols. The macrodiolides synthesized exhibit in vitro cytotoxic activity toward Jurkat, K562, U937, HL-60, HeLa and Hek293 cell lines.