5707-96-0Relevant academic research and scientific papers
Design and synthesis of arylnaphthalene lignan lactone derivatives as potent topoisomerase inhibitors
Chen, Wang,Feng, Zili,Hu, Daihua,Meng, Jin
, p. 856 - 865 (2021/10/21)
Background: Arylnaphthalene lignan lactones are a class of natural products containing the phenyl-naphthyl skeleton. Some arylnaphthalene lignan lactones have been used in clinical practice as antitumor agents, due to their cytotoxicity and inhibitory activities against DNA topoisomerase I (Topo I) and topoisomerase II (Topo II). Objective: This study presents the design and synthesis of arylnaphthalene lignan lactones derivatives. The inhibitory activities against Topo I and Topo IIα and antitumor activities of these compounds were assayed. Methods: A series of arylnaphthalene lignan lactones derivatives have been designed and synthesized, using the Diels-Alder reaction and Suzuki reaction as the key steps. Their antiproliferation activities were evaluated by sulforhodamine B assay on human breast cancer MDAMB-231, MDA-MB-435 and human cervical cancer HeLa cells. DNA relaxation assays were employed to examine the inhibitory activity of compounds 1-22 on Topo I and Topo IIα in vitro. Flow cytometry analysis was performed to study the drug effects on cell cycle progressions. Results: Seven compounds exhibited the modest anti-proliferation activity with IC50 values between 1.36 and 20 μM. Compounds 3, 19 and 22 showed potent inhibitory activities with IC50 values less than 1 μM. DNA relaxation assay revealed that compound 22 showed potent inhibitory activity against Topo IIα in vitro. Compound 22 also induced DNA breaks in MDA-MB-435 cells evidenced by comet tails and the accumulation of γ-H2AX foci. The ability of 22 in inducing DNA breaks mediated by Topo IIα resulted in G2/M phase arrest and apoptosis. Conclusion: This work indicates that arylnaphthalene lignan lactones derivatives represent a novel type of Topo IIα inhibitory scaffold for developing new antitumor chemotherapeutic agents.
Rapid continuous photoflow synthesis of naturally occurring arylnaphthalene lignans and their analogs
Ge, Xiang,Jiang, Haowen,Li, Jinlong
, (2021/05/10)
Naturally occurring arylnaphthalene lignans (ANLs) are subclass of lignans in many dietary or medicinal plants. The progressing interest of ANLs is due to their diversified biological activities. Herein, we developed a convenient method for the preparation of naturally occurring ANLs and their analogs through the continuous photoflow intramolecular Diels–Alder reaction in several minutes under mild conditions with good yields and regioselectivities.
Silver-catalyzed one-pot synthesis of arylnaphthalene lactone natural products
Foley, Patrick,Eghbali, Nicolas,Anastas, Paul T.
experimental part, p. 811 - 813 (2010/09/05)
Naturally occurring arylnaphthalene lactone lignans have demonstrated a variety of valuable medicinal chemistry properties and have therefore been of continued interest to drug discovery research. Our group has demonstrated a silver-catalyzed one-pot synthesis of the arylnaphthalene lactone core using carbon dioxide, phenylpropargyl chloride, and phenylacetylene. This new approach has been employed in the synthesis of six arylnaphthalene lactone natural products: retrochinensin (1), justicidin B (2), retrojusticidin B (3), chinensin (4), justicidin E (5), and taiwanin C (6). Additionally, an arylnaphthalene lactone regioisomer was isolated (9), which we refer to as isoretrojusticidin B.
A new benzannulation reaction and its application in the multiple parallel synthesis of arylnaphthalene lignans
Flanagan, Stuart R,Harrowven, David C,Bradley, Mark
, p. 5989 - 6001 (2007/10/03)
A new aromatic annulation reaction based on sequential Horner-Emmons and Claisen condensation reactions is described. The method is high yielding and provides a rapid entry to arylnaphthalenes. The lignan natural products justicidin B 1, retrojusticidin B 2, taiwanin C 3, justicidin E 4, chinensin 5 and retrochinensin 6 have all been synthesised in good overall yield using this protocol, demonstrating its potential in multiple parallel synthesis. The selective oxidation of diols 34-36 to the corresponding retrolactones with barium manganate(VI) is also noteworthy.
A convenient total synthesis of (+/-)-jatrophan and 2,3-bis-(hydroxymethyl)-6,7-methylenedioxy-1-(3',4'-dimethoxyphenyl)naphthalene, lignan constituents of Jatropha gossypifolia Linn.
Banerji, J,Bose, P,Chakrabarti, R,Das, B
, p. 709 - 712 (2007/10/02)
Convenient synthetic routes to (+/-)-jatrophan and 2,3-bis-(hydroxymethyl)-6,7-methylenedioxy-1-(3',4'-dimethoxyphenyl)naphthalene; the constituents of Jatropha gossypifolia Linn. have been reported.Stobbe condensation of piperonal with dimethyl succinate followed by methylation affords 4-(3',4'-methylenedioxyphenyl)-3-methoxy-carbonyl-methylbut-3-enoate.A second Stobbe condensation with veratraldehyde followed by Bouveault-Blanc reduction affords (+/-)-jatrophan.The aryl naphthalene lignan, 2,3-bis-(hydroxymethyl)-6,7-methylenedioxy-1-(3',4'-dimethoxyphenyl)naphthalene, has been synthesised from jatrophan by oxidative cyclisation followed by lithium aluminum hydride reduction.
SYNTHESIS OF LIGNANS RELATED TO THE PODOPHYLLOTOXIN SERIES
Pelter, Andrew,Ward, Robert S.,Pritchard, Martyn C.,Kay, I. Trevor
, p. 1603 - 1614 (2007/10/02)
The dibenzyl-γ-butyrolactone derivative (6), readily prepared by tandem conjugate addition to but-2-en-4-olide, undergoes cyclisation with trifluoroacetic acid to afford retrochinensin (10).After desulphurisation of (6) with Raney nickel, cyclisation yields the aryltetralin lactone (9).Treatment of (6) with concentrated perchloric acid gives a quantitative yield of the rearranged compound (11), which after appropriate modification can be cyclised to afford either the retro-dihydroarylnaphthalene lactone (13), or the 4-substituted aryltetralin lactone (15).Extension of this approach to a second dibenzylbutyrolactone derivative (21) leads to the retro-dihydroarylnaphthalene lactone (25), but gives only a low yield of the required podophyllotoxin derivative (27).
Synthetic Experiments in Lignans: Part XI - Use of Pyridinium Chlorochromate as a Regioselective Reagent in the Synthesis of 1-Phenylnaphthalene Lactones
Anjaneyulu, A. S. R.,Sastry, Ch. V. M.,Umasundari, P.,Satyanarayana, P.
, p. 305 - 307 (2007/10/02)
Pyridinium chlorochromate has been found to be a regioselective reagent in the oxidation of 2,3-bis(hydroxymethyl)-1-phenylnaphthalenes with preferential attack on 2-hydroxymethyl to yield normal lactones as the major products (>65percent).
HIGHLY REGIOSELECTIVE LACTONE FORMATION CATALYZED BY RUTHENIUM COMPLEXES. AN APPLICATION TO SYNTHESIS OF ARYLNAPHTHALENE LIGNANS
Ishii, Youichi,Ikariya, Takao,Saburi, Masahiko,Yoshikawa, Sadao
, p. 365 - 368 (2007/10/02)
Ruthenium catalyzed hydrogenation of cyclic anhydrides and dehydrogenation of diols have been successfully applied to the highly regioselective synthesis of arylnaphthalene lignans.
Synthetic Experiments in Lignans: Part X - Use of Bis(pyridine)silver Permanganate as a New Reagent for Synthesis of 1-Phenylnaphthalene Lactones
Anjaneyulu, A. S. R.,Umasundari, P.,Sastry, Ch. V. M.
, p. 955 - 956 (2007/10/02)
Bis(pyridine)silver permanganate is found to be a new versatile reagent in the synthesis of 1-phenylnaphthalene lactones from the corresponding 2,3-diols.The synthesis of naturally occurring lactones, viz. justicidin-E, taiwanin-C, retrochinensin, chinensin and justicidin-B has been achieved in improved yields.
A NEW ROUTE TO 1-PHENYLNAPHTHALENES BY CYCLOADDITION: A SIMPLE AND SELECTIVE SYNTHESIS OF SOME NAPHTHALENE LIGNAN LACTONES
Takano, Seiichi,Otaki, Shizuo,Ogasawara, Kunio
, p. 1659 - 1660 (2007/10/02)
2-(2-Dithianyl)benzhydrols (2 a-c) undergo facile cycloaddition reaction with maleic anhydride under thermal conditions to give 1-phenyl-naphthalenes (7 a-c) in one step.The naphthalenes (7 a-c) have been converted into the naphthalene lignan lactones, (9 a-c) and (10 a-c).
