Goniodomic Acid, a Transient Oxirane Intermediate in the Conversion of the Macrolide Algal Toxin Goniodomin A to Seco Acids.

IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL
Constance M Harris, Bernd Krock, Thomas M Harris
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引用次数: 0

Abstract

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 H218O resulted in incorporation of the isotopic label at C32 of the seco acid. Collision-induced dissociation (CID) mass spectrometry of Na+ and NH4+ 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 NH4+. Reversal of GDA-sa formation can occur in the mass spectrometer. CID fragmentation of the 18O-labeled GDA-sa restores the oxirane ring but causes preferential loss of the 18O label from C32.

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来源期刊
CiteScore
7.90
自引率
7.30%
发文量
215
审稿时长
3.5 months
期刊介绍: Chemical Research in Toxicology publishes Articles, Rapid Reports, Chemical Profiles, Reviews, Perspectives, Letters to the Editor, and ToxWatch on a wide range of topics in Toxicology that inform a chemical and molecular understanding and capacity to predict biological outcomes on the basis of structures and processes. The overarching goal of activities reported in the Journal are to provide knowledge and innovative approaches needed to promote intelligent solutions for human safety and ecosystem preservation. The journal emphasizes insight concerning mechanisms of toxicity over phenomenological observations. It upholds rigorous chemical, physical and mathematical standards for characterization and application of modern techniques.
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