Nerolidyl Diphosphate Research Articles

ChemInform Abstract: Epicubenol Synthase and the Stereochemistry of the Enzymatic Cyclization of Farnesyl and Nerolidyl Diphosphate.

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Epicubenol Synthase and the Stereochemistry of the Enzymic Cyclization of Farnesyl and Nerolidyl Diphosphate

Epicubenol Synthase and the Stereochemistry of the Enzymic Cyclization of Farnesyl and Nerolidyl Diphosphate

Trichodiene synthase. Substrate specificity and inhibition.

The substrate specificity of the sesquiterpene synthase trichodiene synthase was examined by determining the Vmax and Km parameters for the natural substrate, trans,trans-farnesyl diphosphate (1), its stereoisomer, cis,trans-farnesyl diphosphate, and the tertiary allylic isomer, (3R)-nerolidyl diphosphate (3), using both the native fungal and recombinant enzymes. A series of farnesyl diphosphate analogs, 15, 16, 20, 7, 8, and 9, was also tested as inhibitors of trichodiene synthase. 10-Fluorofarnesyl diphosphate (15) was the most effective competitive inhibitor, with a K1 of 16 nM compared to the Km for 1 of 87 nM, while the ether analog of farnesyl diphosphate, 8, an extremely potent inhibitor of squalene synthase, showed only modest inhibition of trichodiene synthase, with a K1/Km of 70.

Trichodiene Synthase. Stereochemical Studies of the Cryptic Allylic Diphosphate Isomerase Activity Using an Anomalous Substrate

Incubation of (7S)-6,7-dihydrofarnesyl diphosphate with trichodiene synthase gave, as previously described, a mixture consisting of 80% dihydrofarnesene isomers 6-8 accompanied by 6% trans-6,7-dihydrofarnesol (10) and 13% 6,7-dihydronerolidol (9). The latter product has now been shown to be (3S,7S)-6,7-hydronerolidol [(3S,7S)-9] by direct comparison with synthetic (3S,7S)-6,7-dihydronerolidol and (3RS,7S)-6,7-dihydronerolidol using chiral capillary gas chromatography. The observed formation of (3S,7S)-9 can be accounted for by backside attack of water on an allylic cation-pyrophosphate anion pair generated by syn allylic rearrangement of dihydrofarnesyl diphosphate (5) and ionization of the resulting (3R,7S)-6,7-dihydronerolidyl diphosphate (14). These results provide further support for the proposed isomerization of farnesyl diphosphate (1) to (3R)-nerolidyl diphosphate (3) in the enzymatic formation of trichodiene