144539-72-0Relevant articles and documents
Affinity-Driven Covalent Modulator of the Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Cascade
Chern, Jeffy,Lu, Chun-Ping,Fang, Zhanxiong,Chang, Ching-Ming,Hua, Kuo-Feng,Chen, Yi-Ting,Ng, Cheng Yang,Chen, Yi-Lin Sophia,Lam, Yulin,Wu, Shih-Hsiung
supporting information, p. 7040 - 7045 (2018/05/29)
Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)-(+)-isochaihulactone (1) exhibited significant inhibition against multiple-drug-resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off-target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β-unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI-oriented activity-based proteome profiling. By MS/MS and computer-guided molecular biology approaches, an affinity-driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the “ON/OFF” switch of apoptosis through non-canonically nuclear GAPDH translocation, which bypasses the common apoptosis-resistant route of MDR cancers.
Intramolecular regioselective insertion into unactivated prochiral carbon-hydrogen bonds with diazoacetates of primary alcohols catalyzed by chiral dirhodium(II) carboxamidates. Highly enantioselective total synthesis of natural lignan lactones
Bode,Doyle,Protopopova,Zhou
, p. 9146 - 9155 (2007/10/03)
Intramolecular insertion into unactivated prochiral C-H bonds of 3-aryl-1-propyl diazoacetates catalyzed by dirhodium(II) tetrakis[methyl 1-(3-phenyl propanoyl)imidazolidin-2-one-4(R or S)-carboxylate], Rh2(4R-MPPIM)4 or Rh2(4S-MPPIM)4, occurs in 91-96% ee and with virtually complete regiocontrol for the formation of β-benzyl-γ-butyrolactones. This methodology has been applied to the total synthesis of dibenzylbutyrolactone lignans (-)- and (+)-enterolactone, (-)- and (+)-hinokinin, and (+)-arctigenin from substituted cinnamic acids in 19-27% overall yields. Aryltetralin lignan (+)-isodeoxypodophyllotoxin was prepared from the reactant 3,4-(methylenedioxy)cinnamic acid in 36% yield overall, and the lactone precursor to (+)-isolauricerisinol was formed in 96.5% ee and 23% yield overall. Applications of the chiral Rh2(MPPIM)4 catalysts to fully aliphatic systems resulting in the formation of β-substituted-γ-butyrolactones with high regiocontrol and with 93-96% ee have demonstrated the generality of this methodology. A model that provides accurate predictions of β-substituted-γ-butyrolactone absolute configurations in these asymmetric metal carbene transformations is described.
LIGNANES.10. PREPARATION DES (R)-(+) ET (S)-(-)-β-PIPERONYL ET β-VERATRYL-γ-BUTYROLACTONES ET LEUR UTILISATION DANS LA SYNTHESE TOTALE DE LIGNANES OPTIQUEMENT ACTIFS
Brown, Eric,Daugan, Alain
, p. 141 - 154 (2007/10/02)
A simple and efficient route leading to optically active β-benzyl-γ-butyrolactones is described.Thus, the methyl (R,S)-α-benzylhemisuccinate resulting from a Stobbe condensation with an appropriate aromatic aldehyde, followed by catalytic hydrogenation of the intermediate α-benzylidene hemisuccinic ester, was resolved by means of a chiral base (ephedrine or α-methyl benzylamine).Reduction of each enantiomer, using calcium borohydride, then led to the corresponding optically active β-benzyl-γ-butyrolactone.In this way, the following two lactones were obtained in both (R)-(+) and (S)-(-) enantiomeric forms, β-piperonyl- and β-veratryl-γ-butyrolactones 1 and 2 respectively.These lactones were used as key-intermediates for the syntheses of 17 optically active lignans and lignoids, such as (-)-dimethylmatairesinol (-)-23, (-)-kusunokinin (-)-26 and (+)-dimethylisolariciresinol (+)-35.
