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The first total synthesis of (±)-cyclophostin and (±)-cyclipostin P: inhibitors of the serine hydrolases acetyl cholinesterase and hormone sensitive lipase.

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.

SUBMITTER: Malla RK

PROVIDER: S-EPMC3129627 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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The first total synthesis of (±)-cyclophostin and (±)-cyclipostin P: inhibitors of the serine hydrolases acetyl cholinesterase and hormone sensitive lipase.

Malla Raj K RK Bandyopadhyay Saibal S Spilling Christopher D CD Dutta Supratik S Dupureur Cynthia M CM

Organic letters 20110517 12

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 repor ...[more]

PMID: 21591624

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