Goniodomic Acid, a Transient Oxirane Intermediate in the Conversion of the Macrolide Algal Toxin Goniodomin A to Seco Acids
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide The algal macrolide goniodomin A (GDA) undergoes ring-cleavage under unusually mild, alkaline conditions to form mixtures of stereoisomers of seco acids GDA-sa and iso-GDA-sa. In the primary fragmentation pathway, opening of the macrolide ring occurs by displacement of the carboxyl group by a base-catalyzed attack of the C32 hemiketal hydroxy group on C31, yielding an oxirane-carboxylic acid, named goniodomic acid. The oxirane ring is unstable, undergoing solvolytic opening to form mainly GDA-sa. Experimental support for this pathway obtained by carrying out the ring-opening reaction in H 2 18 O resulted in incorporation of the isotopic label at C32 of the seco acid. Collision-induced dissociation (CID) mass spectrometry of Na + and NH 4 + ion adducts was employed to establish that ring-opening of the macrolide ring occurred by alkyl-O cleavage. Fragmentation was dominated by Grob–Wharton decarboxylation and retro-Diels–Alder reactions of the labeled seco acids. Direct observation of goniodomic acid was achieved when the ring-opening reaction was carried out under anhydrous conditions. A minor alkyl-O cleavage pathway gives rise to iso-GDA-sa by allylic attack at C29 of GDA or of the oxirane. In the formation of both GDA-sa and iso-GDA-sa, ring-opening is likely to be catalyzed by Na + and NH 4 + . Reversal of GDA-sa formation can occur in the mass spectrometer. CID fragmentation of the 18 O-labeled GDA-sa restores the oxirane ring but causes preferential loss of the 18 O label from C32.
Source: Chemical Research in Toxicology
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Award: G930214164
OpenAlex ID: W4405705314