C20 heptaenyl diphosphonate 4 was prepared for one-pot synthesis of carotenoids 1. Olefination with various aromatic aldehydes allowed fast assembly of the corresponding carotenoids. The SAR of carotenoids was investigated by high-throughput screening of ABTS and DPPH assays and their hierarchical clustering analysis. Antioxidant activity of carotenoids increased with the number of electron-donating substituents. Carotene 1a with multiple electron-donating substituents was most proficient, which showed better radical scavenging activities than β-carotene and lycopene.