Issue 5, 2009

6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase

Abstract

The catalytic mechanism of the enzyme aristolochene synthase from Penicillium roqueforti (PR-AS) has been probed with the farnesyl diphosphate analogues 6- and 14-fluoro farnesyl diphosphate (1b and 1c). Incubation of these analogues with PR-AS followed by analysis of the reaction products by GC-MS and NMR spectroscopy indicated that these synthetic FPP analogues were converted to the fluorinated germacrene A analogues 3b and 3c, respectively. In both cases the position of the fluorine atom prevented the formation of the eudesmane cation analogues 4b and 4c. These results highlight that germacrene A is an on-path reaction intermediate during PR-AS catalysis and shed light on the mechanism by which germacrene A is converted to eudesmane cation. They support the proposal that the role of PR-AS in the cyclisation is essentially passive in that it harnesses the inherent chemical reactivity present in the substrate by promoting the initial ionisation of farnesyl diphosphate and by acting as a productive template to steer the reaction through an effective series of cyclisations and rearrangements to (+)-aristolochene (7a).

Graphical abstract: 6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase

Supplementary files

Article information

Article type
Paper
Submitted
01 Oct 2008
Accepted
28 Nov 2008
First published
20 Jan 2009

Org. Biomol. Chem., 2009,7, 962-975

6- and 14-Fluoro farnesyl diphosphate: mechanistic probes for the reaction catalysed by aristolochene synthase

D. J. Miller, F. Yu, D. W. Knight and R. K. Allemann, Org. Biomol. Chem., 2009, 7, 962 DOI: 10.1039/B817194G

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