title: Stability of cyclic imine toxins: interconversion of pinnatoxin amino ketone and pinnatoxin A in aqueous media.
abstract: Pinnatoxins belong to the cyclic imine (CI) group of marine toxins with a unique toxicological profile. The need for structural integrity of the aliphatic 7-membered cyclic imine for the potent bioactivity of pinnatoxins has been experimentally demonstrated. In this study, we probe interconversion of the natural cyclic imine and its open form, pinnatoxin A amino ketone (PnTX AK), under physiologically relevant aqueous conditions. Our studies demonstrate the high stability of PnTX A. The unusual stability of the imine ring in PnTX A has implications for its oral toxicity and detoxification. These studies, as well the access to PnTX amino ketone, were enabled by the total synthesis of (+)-pinnatoxin A completed previously in our laboratory.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106-9510, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Jackson
authors.forename: Craig E
authors.initials: CE
authors.lastname: Stivala
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.forename: Jordi
authors.initials: J
authors.lastname: Molgó
authors.forename: Armen
authors.initials: A
authors.lastname: Zakarian
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008387:Marine Toxins / Q000737:chemistry*; D015394:Molecular Structure; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000470:Alkaloids; D007097:Imines; D007659:Ketones; D008387:Marine Toxins; D013141:Spiro Compounds; C447983:pinnatoxin A