17187-82-5Relevant academic research and scientific papers
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.
Isochaihulactone analogues: Synthesis and anti-proliferative activity of novel dibenzylbutyrolactones
Alizadeh, Babak Heidary,Foroumadi, Alireza,Emami, Saeed,Khoobi, Mehdi,Panah, Fatemeh,Ardestani, Sussan K.,Shafiee, Abbas
experimental part, p. 5979 - 5984 (2011/01/13)
A series of dibenzyl-γ-butyrolactones bearing a hydroxyl group at the benzylic position of 3-benzyl group were synthesized as hydrated analogue of isochaihulactone and evaluated against breast cancer human cell lines (MDA-M231, MCF-7 and T47D). The target compounds were synthesized in 7 steps from known lactone; (S)-(+)-γ-benzyloxymethyl-γ-butyrolactone. The key step was the aldol condensation between (+)-(R)-β-(benzo[d][1,3]dioxol-5-ylmethyl)- γ-butyrolactone and substituted benzaldehydes which afforded corresponding α-hydroxybenzyl butyrolactone analogues. The cytotoxic study of the synthesized compounds against breast cancer human cell lines showed that some of them inhibit breast cancer human cell proliferation with percentage inhibitions over 50% at concentrations less than 50 μg/mL.
Diastereoselective synthesis of β-piperonyl-γ-butyrolactones from Morita-Baylis-Hillman adducts. highly efficient synthesis of (±)-yatein, (±)-podorhizol and (±)-epi-podorhizol
Trazzi, Giordano,Andre?, Marcelo Fabiano,Coelho, Fernando
experimental part, p. 2327 - 2339 (2011/10/09)
Starting from a Morita-Baylis-Hillman adduct we describe a simple and very efficient method for the diastereoselective preparation of hydroxylated β-piperonyl-γ-butyrolactones. To exemplify the efficiency of this approach we also describe a highly efficie
Asymmetric Synthesis of Dibenzylbutyrolactones and Aryltetralin Lignan Lactones by Tandem Cojugate Addition to a Chiral Butenolide
Pelter, Andrew,Ward, Robert S.,Jones, D. Martin,Maddocks, Peter
, p. 2621 - 2630 (2007/10/02)
Addition of sulfur-stabilised carbanions to (-)-5-(1-menthyloxy)furan-2(5H)-one followed by reaction with an aromatic aldehyde affords a short synthesis of enantiomerically pure dibenzylbutyrolactone derivatives.Desulfurisation with NaBH4/NiCl2 proceeds in almost quantitative yield, and reduction with NaBH4/KOH gives the parent dibenzylbutyrolactones including (-)-6-epi-podorhizol.These undergo cyclisation with acid to give homochiral aryltetralines including (-)-deoxyisopodophyllotoxin in high yield.
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.
A SHORT VERSATILE SYNTHESIS OF ARYLTETRALIN LIGNANS INCLUDING DEOXYISOPODOPHYLLOTOXIN AND EPI-ISOPODOPHYLLOTOXIN
Pelter, Andrew,Ward, Robert S.,Pritchard, Martyn C.,Kay, I. Trevor
, p. 1615 - 1624 (2007/10/02)
Cyclisation of tandem conjugate addition products (10), (15), and (20), prepared by reaction of anions derived from benzyl phenyl and benzyl t-butyl sulphides with but-2-en-4-olide, affords a series of aryltetralin lignans belonging to either the 'normal' or the 'retro' lactone series.Desulphurisation of compound (15) followed by cyclisation, or desulphurisation of the cyclised product (22b), affords deoxyisopodophyllotoxin (5), while treatment of compound (22b) with mercury(II) trifluoroacetate yields epi-isopodophyllotoxin (6).
Oxidative Coupling of Lignans. III. Non-Phenolic Oxidative Coupling of Deoxypodorhizon and Related Compounds
Cambie, Richard C.,Craw, Peter A.,Rutledge, Peter S.,Woodgate, Paul D.
, p. 897 - 918 (2007/10/02)
Oxidative coupling of deoxypodorhizon (4) with thallium(III) oxide and trifluoroacetic acid may be controlled to give either deoxyisopodophyllotoxin (14) or isostegane (16).These results and those with related non-phenolic substances indicate that the aromatic substituents of the parent diarylbutane play an important role in determining the outcome of oxidative coupling.
AN EASY PREPARATION OF (-) AND (+)-β-PIPERONYL-γ-BUTYROLACTONES, KEY-INTERMEDIATES FOR THE SYNTHESIS OF OPTICALLY ACTIVE LIGNANS
Brown, Eric,Daugan, Alain
, p. 3997 - 3998 (2007/10/02)
Methyl α-piperonylhemisuccinate was resolved into both its (R)-(+) and (S)-(-)-antipodes by (-) and (+)-ephedrine, respectively.Calcium borohydride reduction of the (R)-(+) and (S)-(-)-hemiesters afforded the crystalline, optically pure, (R)-(+) and (S)-(
SYNTHESES TOTALES ET ETUDES DE LIGNANES BIOLOGIQUEMENT ACTIFS-II. APPLICATION DE L'α-HYDROXYALKYLATION DE β-BENZYL χ-BUTYROLACTONE A LA CREATION DES SQUELETTES PHENYL TETRALINE ET BISBENZOCYCLOOCTADIENES. SYNTHESE TOTALE DU (+/-) PODORHIZOL, DE LA (+/-) P
Robin, Jean-Pierre,Dhal, Robert,Brown, Eric
, p. 3667 - 3671 (2007/10/02)
The use of lithium hexamethyldisilylamide (LHDS) in α-hydroxyalkylation of β-(3,4-methylenedioxybenzyl)-χ-butyrolactone gives high yields of (+/-) podorhizol and (+/-) epi-podorhizol as a 1:1 diastereoisomer mixture.Cyclisation of both alcohols using trif
