title: Synthesis of optically pure norcantharidin analogue NCA-01, a highly selective protein phosphatase 2B inhibitor, and its derivatives.
abstract: An efficient synthetic route to optically pure norcantharidin analogue NCA-01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X-ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B-inhibitory activities of NCA-01 and its derivatives were independent of the enantiomeric form. NCA-01 dimethyl ester potently inhibited IL-2 production in Jurkat cells.
authors.affiliation: RIKEN Advanced Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Masato
authors.initials: M
authors.lastname: Iizuka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Matsukura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hashizume
authors.forename: Mikiko
authors.initials: M
authors.lastname: Sodeoka
mesh_terms: D001665:Binding Sites; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D017434:Protein Structure, Tertiary; D013237:Stereoisomerism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007376:Interleukin-2; C574819:NCA-01; C069741:norcantharidin; D019703:Calcineurin