Maitotoxin (MTX) was first discovered as one of the toxins responsible for ciguatera seafood poisoning and later found to be a product of the epiphytic dinoflagellate Gambierdiscus toxicus. MTX is one of the largest non-biopolymer (MW 3422) and most toxic against mammals (50 ng/kg) known to date. MTX elicits remarkable biological activities at extremely low concentration, for instance, hemolysis (15 nM) of red blood cells and calcium ion influx (0.3 nM) in all cell types examined to date. Despite a large number of pharmacological and biophysical investigations, the precise mode of action of MTX has not been elucidated at the molecular level, primarily due to the limited availability of MTX from natural sources. As a part of the structure-activity relationship studies of MTX based on the chemical synthesis of partial structures of MTX, the C’D’E’F’, WXYZA’B’C’, QRS, NOPQR(S), and LMNO ring systems were synthesized. By using these fragments, inhibitory activity against MTX-induced calcium ion influx was evaluated.