3 research outputs found

    Alternative Synthesis of the Colorado Potato Beetle Pheromone

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    A concise preparation of the pheromone secreted by the male Colorado potato beetle [viz. (3<i>S</i>)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one] was accomplished in four steps starting from 2-fluoronerol or 2-fluorogeraniol. The key step in the synthesis involves a 6-endo epoxide ring-opening with ester participation that simultaneously inverts the 3<i>R</i>-configuration of the (3<i>R</i>)-2,3-epoxy-2-fluoroprenyl acetate intermediate and installs the ketone functionality of the semiochemical. Extensive NMR studies validate the proposed 6-endo mechanism of the featured rearrangement, which under anhydrous conditions resulted in the formation of two bicyclic 1,3-dioxan-5-ones via an unprecedented intramolecular Prins cyclization

    Synthesis of Methylerythritol Phosphate Analogues and Their Evaluation as Alternate Substrates for IspDF and IspE from <i>Agrobacterium tumefaciens</i>

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    The methylerythritol phosphate biosynthetic pathway, found in most Bacteria, some parasitic protists, and plant chloroplasts, converts d-glyceraldehyde phosphate and pyruvate to isopentenyl diphosphate (<b>IPP</b>) and dimethylallyl diphosphate (<b>DMAPP</b>), where it intersects with the mevalonate pathway found in some Bacteria, Archaea, and Eukarya, including the cytosol of plants. d-3-Methylerythritol-4-phosphate (<b>MEP</b>), the first pathway-specific intermediate in the pathway, is converted to <b>IPP</b> and <b>DMAPP</b> by the consecutive action of the IspD-H proteins. We synthesized five d-<b>MEP</b> analoguesd-erythritol-4-phosphate (<b>EP</b>), d-3-methylthrietol-4-phosphate (<b>MTP</b>), d-3-ethylerythritol-4-phosphate (<b>EEP</b>), d-1-amino-3-methylerythritol-4-phosphate (<b>NMEP</b>), and d-3-methylerythritol-4-thiolophosphate (<b>MESP</b>)and studied their ability to function as alternative substrates for the reactions catalyzed by the IspDF fusion and IspE proteins from <i>Agrobacterium tumefaciens</i>, which covert <b>MEP</b> to the corresponding eight-membered cyclic diphosphate. All of the analogues, except <b>MTP</b>, and their products were substrates for the three consecutive enzymes

    Structural Elucidation of Cisoid and Transoid Cyclization Pathways of a Sesquiterpene Synthase Using 2-Fluorofarnesyl Diphosphates

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    Sesquiterpene skeletal complexity in nature originates from the enzyme-catalyzed ionization of (<i>trans</i>,<i>trans</i>)-farnesyl diphosphate (FPP) (<b>1a</b>) and subsequent cyclization along either 2,3-transoid or 2,3-cisoid farnesyl cation pathways. Tobacco 5-epi-aristolochene synthase (TEAS), a transoid synthase, produces cisoid products as a component of its minor product spectrum. To investigate the cryptic cisoid cyclization pathway in TEAS, we employed (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) as an alternative substrate. Strikingly, TEAS was catalytically robust in the enzymatic conversion of (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) to exclusively (≥99.5%) cisoid products. Further, crystallographic characterization of wild-type TEAS and a catalytically promiscuous mutant (M4 TEAS) with 2-fluoro analogues of both all-<i>trans</i> FPP (<b>1a</b>) and (<i>cis</i>,<i>trans</i>)-FPP (<b>1b</b>) revealed binding modes consistent with preorganization of the farnesyl chain. These results provide a structural glimpse into both cisoid and transoid cyclization pathways efficiently templated by a single enzyme active site, consistent with the recently elucidated stereochemistry of the cisoid products. Further, computational studies using density functional theory calculations reveal concerted, highly asynchronous cyclization pathways leading to the major cisoid cyclization products. The implications of these discoveries for expanded sesquiterpene diversity in nature are discussed
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