Abstract
The first total synthesis of dispyrin, a recently reported bromopyrrole alkaloid from Agelas dispar with an unprecedented bromopyrrole tyramine motif, was achieved in three steps on a gram scale (68.4% overall). No biological activity was reported for dispyrin, so we evaluated synthetic dispyrin against>200 discrete molecular targets in radioligand binding and functional assays. Unlike most marine natural products, dispyrin (1) possesses no antibacterial or anticancer activity, but was found to be a potent ligand and antagonist of several therapeutically relevant GPCRs, the alpha1D and alpha2A adrenergic receptors and the H2 and H3 histamine receptors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenergic Agonists* / chemical synthesis
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Adrenergic Agonists* / chemistry
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Adrenergic Agonists* / pharmacology
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Agelas / chemistry*
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Alkaloids* / chemical synthesis
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Alkaloids* / chemistry
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Alkaloids* / pharmacology
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Animals
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Drug Screening Assays, Antitumor
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Histamine Agents* / chemical synthesis
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Histamine Agents* / chemistry
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Histamine Agents* / pharmacology
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Hydrocarbons, Brominated* / chemical synthesis
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Hydrocarbons, Brominated* / chemistry
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Hydrocarbons, Brominated* / pharmacology
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Ligands
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Marine Biology
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Microbial Sensitivity Tests
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Molecular Structure
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Pyrroles* / chemical synthesis
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Pyrroles* / chemistry
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Pyrroles* / pharmacology
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Receptors, G-Protein-Coupled / agonists
Substances
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Adrenergic Agonists
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Alkaloids
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Histamine Agents
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Hydrocarbons, Brominated
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Ligands
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Pyrroles
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Receptors, G-Protein-Coupled
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dispyrin