Abstract
A convenient and economical synthesis of 4-hydroxy-2,3-dimethoxybenzaldehyde has been developed. This was used as the starting material for the first total syntheses of (+/-)-isopiline, (+/-)-preocoteine, (+/-)-oureguattidine and (+/-)-3-methoxynordomesticine in which the key step involved formation of ring C of the aporphines by a radical-initiated cyclisation. Although (+/-)-3-methoxynordomesticine possesses weak antimicrobial activity, it inhibits the production of nitric oxide (NO), prostaglandin (PG)E(2), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 and the expression of inducible nitric oxide synthase (iNOS) and cycloxygenase (COX)-2 in macrophages stimulated with LPS in vitro.
MeSH terms
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Animals
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Anti-Bacterial Agents / chemical synthesis*
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology
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Aporphines / chemical synthesis*
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Aporphines / chemistry
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Aporphines / pharmacology
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Candida albicans / drug effects
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Cell Line
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / metabolism
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Cytokines / antagonists & inhibitors
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Dinoprostone / antagonists & inhibitors
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Dose-Response Relationship, Drug
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Escherichia coli / drug effects
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Lipopolysaccharides / pharmacology
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Mice
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Microbial Sensitivity Tests
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Nitric Oxide / antagonists & inhibitors
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Staphylococcus aureus / drug effects
Substances
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Anti-Bacterial Agents
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Anti-Inflammatory Agents, Non-Steroidal
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Antifungal Agents
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Aporphines
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Cytokines
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Lipopolysaccharides
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Nitric Oxide
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Ptgs2 protein, mouse
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Cyclooxygenase 1
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Cyclooxygenase 2
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Dinoprostone