The conjugated tetraacetylenic natural product (S)-18-hydroxyminquartynoic acid (2) is synthesized in five linear steps and 17.7% overall yield from commercially available 1,2,5,6-O-diisopropylidene mannitol. The key step is a one-pot three-component Cadiot-Chodkiewicz reaction affording the tetrayne unit. The oxygen-substituted bromoalkyne 10 was found to react at a much faster rate than the non-oxygen-substituted bromoalkyne 6 in the key step. The undesired symmetric cross-coupling by 10 generates a symmetric tetrayne intermediate, which undergoes a nucleophilic addition by 1 equiv of ethylamine. This side reaction is suppressed by controlling the order and rate of addition of each component and by reducing the amount of ethylamine.