In this work, the synthesis of highly biologically active acetylene diols was studied for the first time based on the reaction of the nucleophilic coupling of terminal acetylene alcohols with aliphatic, alicyclic, aromatic and heterocyclic substituents in their molecule with acetone, methyl butyl ketone and methyl tertbutyl ketones using the CaO/NH3/Et2O catalytic system. Based on the influence of the structure, nature and chemical activity of selected molecules of acetylene alcohols and ketones on the course of the reaction and the yield of products, a relative series of productivity yields of acetylene diols has been developed. Various factors influencing the synthesis process and the yield of acetylene diol products have been systematically studied - temperature, reaction duration, nature of catalysts and solvents, amounts of reagents and substrates, types and amounts of intermediates and by-products formed in the reaction. Based on the results obtained, the most optimal conditions for the nucleophilic coupling process were determined and reaction mechanisms were proposed. The synthesized esters have been identified, and their partial constants, structure, purity and composition have been proven using modern physicochemical methods.