Investigation of 44-methylgambierone reactivity with periodate: Structural reassignment, solvent instability and formation of a furanoid analogue.

Autor: Mudge EM; Biotoxin Metrology, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada. Electronic address: elizabeth.mudge@nrc-cnrc.gc.ca., Wilkins AL; School of Science, University of Waikato, Private Bag 3105, Hamilton, 3240, New Zealand., Murray JS; Cawthron Institute, Private Bag 2, Nelson, 7040, New Zealand., Rise F; Department of Chemistry, University of Oslo, Blindern, P.O. Box 1033, NO-0315, Oslo, Norway., Miles CO; Biotoxin Metrology, National Research Council Canada, 1411 Oxford Street, Halifax, NS, B3H 3Z1, Canada; Norwegian Veterinary Institute, P.O. Box 64, 1431, Ås, Norway.
Jazyk: angličtina
Zdroj: Toxicon : official journal of the International Society on Toxinology [Toxicon] 2024 Nov 28; Vol. 251, pp. 108154. Date of Electronic Publication: 2024 Oct 25.
DOI: 10.1016/j.toxicon.2024.108154
Abstrakt: Gambierones are sulfated polyethers produced by benthic dinoflagellates in the genera Gambierdiscus, Coolia and Fukuyoa. While relative toxicity data for gambierones suggests they are low compared with ciguatoxin analogues, gambierones have been suggested for use as marker compounds for environmental monitoring programs for the presence of Gambierdiscus in marine waters. The published structure of gambierone and analogues of it, including 44-methylgambierone (44-MeGAM), have been reported to possess 1,2- and 4,5-cis diols, while only the 1,2- diol unit has been shown to undergo periodate oxidation. An in-depth analysis of previously reported NMR data for 44-MeGAM in CD 3 OD showed that the C-4 stereochemistry of 44-MeGAM and other gamberiones was mis-assigned, that the 4-CH 2 -CHOH-CH 2 OH and OH groups are equatorially and axially oriented, respectively, rather than vice versa as previously reported. This re-examination of existing 44-MeGAM NMR data also showed that its C-12 and C-13 assignments (and those for other gambierones) should be reversed. In an effort to better understand the C-4 stereochemical and periodate reaction characteristics of gambierones (C-4 is an epimerizable hemiacetal carbon), additional NMR data was acquired in D 6 -DMSO. Unexpectedly, progressive conversion of 44-MeGAM to a long-term stable ring-A furanoid analogue was observed. A subsequent series of microscale stability trials identified several solvents that affected the solution-stability of 44-MeGAM, and these findings should be taken into consideration during isolation, handling, storage and bioassay evaluations of gambierones in future studies.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J. Sam Murray reports financial support was provided by Ministry of Business Innovation and Employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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