Structure Determination, Chemical Synthesis, and Evaluation of Biological Activity of Super Carbon Chain Natural Products

Abstract

Abstract Marine microorganisms are known to produce natural products, so called super carbon chain compounds whose molecular weights (MWs) exceed one thousand, such as amphidinol 3 (AM3) and maitotoxin (MTX). AM3 (MW 1328) is a long linear compound containing polyol, bis-tetrahydopyran, and polyene moieties, and elicits potent antifungal activities. During the course of our studies on AM3, originally proposed absolute configuration was revised by the chemical synthesis of partial structures in combination with degradation of the natural product. Furthermore, the first total synthesis of AM3 has been achieved based on the convergent method via three components coupling. In addition, we have succeeded in design and synthesis of an artificial truncated analog of AM3 which elicits comparable antifungal activity with those of the natural product. On the other hand, MTX (MW 3422) is a ladder-shaped polyether comprised of thirty-two cyclic ethers, and it elicits potent Ca2+ influx activity. During the course of our structure-activity relationship studies of MTX, we have developed three methods for synthesizing ladder-shaped polyethers via two-ring construction through the coupling of two fragments. The synthetic partial structures corresponding to the hydrophobic parts of MTX inhibited the Ca2+ influx induced by MTX.