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

Hunter, A Christy, Oni, Yewande Inatimi, Dodd, Howard T , Raftery, James, Gardiner, John M and Uttley, Megan (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 (BBA)-Molecular and Cell Biology of Lipids, 1862 (9). pp. 939-945. ISSN 1388-1981

Full content URL: https://doi.org/10.1016/j.bbalip.2017.06.003

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Item Type:Article
Item Status:Live Archive

Abstract

The 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.

Divisions:College of Science > School of Pharmacy
ID Code:45548
Deposited On:29 Jun 2021 15:59

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