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dc.contributor.authorHunter, Alan Christyen
dc.contributor.authorOni, Yewande Inatimien
dc.contributor.authorDodd, Howard T.en
dc.contributor.authorRaftery, Jamesen
dc.contributor.authorGardiner, John M.en
dc.contributor.authorUttley, Meganen
dc.date.accessioned2017-07-25T10:54:22Z
dc.date.available2017-07-25T10:54:22Z
dc.date.issued2017-06-09
dc.identifier.citationHunter, A.C et al. (2017) Metabolism of steroidal lactones by the fungus Corynespora cassiicola CBS 161.60 results in a mechanistically unique intramolecular ring-D cyclization resulting in C-14 spiro-lactones,Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1862 (9), pp. 939-945en
dc.identifier.issn1388-1981
dc.identifier.urihttp://hdl.handle.net/2086/14329
dc.descriptionThe file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.en
dc.description.abstractThe fungus Corynespora cassiicola metabolises exogenous steroids in a unique and highly specific manner. Central to this, is the ability of this organism to functionalise substrates (androgens, progestogens) at the highly stereochemically hindered 8β-position of the steroid nucleus. A recent study has identified that 8β-hydroxylation occurs through inverted binding in a 9α-hydroxylase. In order to discern the metabolic fate of more symmetrical molecules, we have investigated the metabolism of a range of steroidal analogues functionalised with ring-D lactones, but differing in their functional group stereochemistry at carbon-3. Remarkably, the 3α-functionalised steroidal lactones underwent a mechanistically unique two step intramolecular cyclisation resulting in the generation of a ring-D spiro-carbolactone. This rapid rearrangement initiated with hydroxylation at carbon 14 followed by transesterification, resulting in ring contraction with formation of a butyrolactone at carbon-14. Remarkably this rearrangement was found to be highly dependent on the stereochemistry at carbon-3, with the β-analogues only undergoing 9α-hydroxylation. The implications of these findings and their mechanistic bases are discussed.en
dc.language.isoenen
dc.publisherElsevieren
dc.subjectCorynespora cassiicolaen
dc.subjectLactoneen
dc.subjectSpiro-carbonen
dc.subjectSteroiden
dc.subjectCyclizationen
dc.subjectTransesterificationen
dc.titleMetabolism of steroidal lactones by the fungus Corynespora cassiicola CBS 161.60 results in a mechanistically unique intramolecular ring-D cyclization resulting in C-14 spiro-lactonesen
dc.typeArticleen
dc.identifier.doihttps://doi.org/10.1016/j.bbalip.2017.06.003
dc.peerreviewedYesen
dc.explorer.multimediaNoen
dc.funderN/Aen
dc.projectidN/Aen
dc.cclicenceCC-BY-NC-NDen
dc.date.acceptance2017-06-07en
dc.researchinstituteLeicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)en


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