Maitotoxin (MTX) is a ladder-shaped polycyclic ether produced by the epiphytic dinoflagellate Gambierdiscus toxicus. MTX elicits potent Ca2+ influx activity. During the course of our structure-activity relationship studies of MTX by using chemically-synthesized model compounds corresponding to its partial structures, the C’D’E’F’ and WXYZA’B’C’ ring system have inhibited the MTX-induced Ca2+ influx (IC50 59 and 30 μM, respectively). Herein, we report synthesis and bioactivity other partial structures of MTX. We synthesized the hydrophobic part corresponding to the QRS ring system, and found that it elicited inhibitory activity (IC50 44 μM) hydrophobic comparable to above two partial structures. In order to explore the importance of the hydrophilic region, not only the LMNO ring but also its enantiomer were synthesized. They showed only weak inhibitory activity and there was no significant difference between the enantiomers. The amphiphilicity is one of the characteristic properties of MTX. Therefore, we synthesized the NOPQRS ring system corresponding to the border part of hydrophobic and hydrophilic region of MTX. It is interesting to note that the compound elicited no inhibitory activity, suggesting that presence of both hydrophobic and hydrophilic parts influenced the biological activity in contradictory manners
