Polycavernosides and gambierol: Chemistry, pharmacology, toxicology, and detection

Polycavernoside A (PA, Figure 28.1) was isolated by Yasumoto and his colleagues with a minor analog polycavernoside B (PB) as the causative toxin of the human fatal poisoning occurred in Guam in 1991, resulting from ingestion of the red alga Gracilaria edulis.1,2 Out of 13 patients, 3 were killed. PA was also identi6 ed in the same alga that caused the poisoning, killing 8 out of 36 patients in Philippines in 2002-2003.3 The planar structures of PA2 and four minor analogs, polycavernoside A2 (PA2), A3 (PA3), B (PB), and B2 (PB2) (Figure 28.2) were determined.4 All these polycavernosides possess the same macrolide aglycon containing a 6 ve-member cyclohemiacetal adjacent to a ketone at C9. Structural variation among these analogs are in the conjugated diene (PB, PB2) or triene (PA, PA2, PA3) side chain at C15, and in O-methylated or O-acetylated l-fucosyl-d-xylose sugar unit at C5. Yotsu-Yamashita et al. also isolated other two minor analogs, polycavernoside C (PC) and polycavernoside C2 (PC2), from G. edulis collected in Guam in 1991-1992, and their structures were recently determined (Figure 28.1).5 PC and PC2 have a common aglycon structure, that is distinctly different from that of PA and other analogs.