Two new skeletal analogues of saxitoxin found in the scallop, Patinopecten yessoensis, as possible metabolites of paralytic shellfish toxins

The scallop, Patinopecten yessoensis, was screened for new saxitoxin analogues to study the metabolism of paralytic shellfish toxins (PSTs), and this resulted in the discovery of two new analogues: M5-hemiaminal (HA) and M6-HA. M5-HA was isolated and its structure was determined by using NMR spectroscopy. It contains hydrogen at C-4 with opposite stereochemistry to that in saxitoxin, and a hemiaminal was formed between 9-NH2 and the hydrated ketone at C-12 in alpha-orientation. This is the first reported structural feature in a natural saxitoxin analogue, whereas the same ring system has previously been reported in a synthetic saxitoxin analogue, FD-saxitoxin. Acid hydrolysis of the carbamoyl N-sulfate in M5-HA produced M6-HA which was also identified in P. yessoensis by using LC-MSMS. M5-HA was not synthetically produced from M1 (11-hydroxy gonyautoxin-5) and M3 (11,11-dihydroxy gonyautoxin-5) through incubation in aqueous buffers. Furthermore, PSTs in the hepatopancreas of P. yessoensis, cultured in a bay located in northeastern Japan, were chronologically analyzed in 2018. The highest concentrations of M1/M3/M5-HA were observed two weeks after C-toxins had reached their highest concentrations, which provides evidence that M1/M3/M5-HA are metabolites of C-toxins. The voltage-gated sodium channel blockage activity of M6-HA was not detected at the concentration of 140 nM by using the Neuro-2A veratridine/ouabain assay. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study identified two new saxitoxin analogues, M5-HA and M6-HA, with M5-HA having a unique stereochemical structure different from saxitoxin. Acid hydrolysis of M5-HA produced M6-HA, and further analysis confirmed M1/M3/M5-HA as metabolites of C-toxins.