Abstract
Cyclophostin, a structurally unique and potent naturally occurring acetyl cholinesterase (AChE) inhibitor, and its unnatural diastereomer were prepared in 6 steps and 15% overall yield from hydroxymethyl butyrolactone. The unnatural diastereomer of cyclophostin was converted into cyclipostin P, a potent naturally occurring hormone sensitive lipase (HSL) inhibitor, using a one pot dealkylation-alkylation process. The inhibition [IC(50)] of human AChE by cyclophostin and its diastereomer are reported, as well as constituent binding (K(I)) and reactivity (k(2)) constants.
© 2011 American Chemical Society
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cholinesterase Inhibitors / chemical synthesis*
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Cholinesterase Inhibitors / chemistry
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Cholinesterase Inhibitors / pharmacokinetics
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Cholinesterase Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Lipase / antagonists & inhibitors*
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Molecular Structure
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Organophosphorus Compounds / chemical synthesis*
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Organophosphorus Compounds / chemistry
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Organophosphorus Compounds / pharmacokinetics
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Organophosphorus Compounds / pharmacology*
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Stereoisomerism
Substances
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Cholinesterase Inhibitors
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Organophosphorus Compounds
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cyclipostin P
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cyclophostin
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Lipase