Abstract
The total synthesis of both the double bond isomers of indolizine alkaloid 8-deoxypumiliotoxin 193H has been accomplished. Both the double bond isomers Z-4 and E-4 induced convulsions and inhibited neuro-muscular activity at a dose of 25 mg/kg after intraperitoneal injection in mice. The lethal dose of Z-4 and E-4 was 100 mg/kg, indicating that 8-deoxypumiliotoxin 193H is 10-times less toxic than the known pumiliotoxin (+)-251 D.
Keywords:
Total synthesis; deoxypumiliotoxin 193H; in vivo studies; stereoselectivity.
MeSH terms
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Alkaloids / administration & dosage
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Alkaloids / chemical synthesis*
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Alkaloids / chemistry
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Alkaloids / pharmacology*
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Alkaloids / toxicity
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Animals
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Body Temperature / drug effects
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Dose-Response Relationship, Drug
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Indolizines / chemistry
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Indolizines / pharmacology
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Injections, Intraperitoneal
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Isomerism
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Male
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Mice
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Mice, Inbred Strains
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Muscle Strength / drug effects*
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Piperidines / chemistry
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Piperidines / pharmacology
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Rotarod Performance Test
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Seizures / chemically induced
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Structure-Activity Relationship
Substances
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Alkaloids
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Indolizines
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Piperidines
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indolizine
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pumiliotoxin A