| Research Abstract |
Polycavernoside A (PA, Figure 1) and B (PB) were isolated as the causative toxins of the human fatal poisoning (3 death/15 patients) occurred in Guam in 1991, resulting from ingestion of the red alga, Gracilaria edulis. PA was also identified from the same alga and Acanthophora specifera, wihch also caused fatal poisoning (8 death/36 patients) in Philippines in 2002-2003. We determined the planar structures of PA and the analogs, PA2, PA3, PB, and PB2, which possess the same macrolide aglycon structure. Structural variation among these analogs are in the conjugated diene or triene side chain at C15, and in 0-methylated or O-acetylated L-fucosyl-D-xylose sugar part at C5. We isolated two other minor analogs, polycavernoside C (PC, 1) and C2 (PC2, 2) (0.1-0.2 mg for each), from G. edulis in 1992-1994 collected in Guam. These were suggested to have a common aglycon structure, and to be the first analogs which have the different aglycon structure from that of PA. We determined the relative stereostructure of 1 and the absolute structure of 2 deduced by spectroscopic analysis and synthesis of the model of their aglycon (3b).
Biological activity of 2 and probable origin of polycavernosides
The mouse (ddY, male, 12 g) administrated 2 (2.4 μg, i.p.) did not show any symptoms and survived, suggesting the value of LD99 for 2 was more than 0.2 mg/kg. 3b did not show cytotoxicity at 20 μM in two cell lines, mouse neuroblastoma cells (Neuro-2a) and human acute monocytic leukemia cells (THP-1), by WST-8 assay (Dojindo, Japan).
Cyanobacterium was proposed for the origin of polycavernosides.^3 The structures of 1 and 2 provide information for the biosynthetic pathway or metabolism of polycavernosides, which are necessary for monitoring the occurrence of these human lethal toxins.
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