- Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
-
Podophyllotoxin is probably the most prominent representative of lignan natural products. Deoxy-, epi-, and podophyllotoxin, which are all precursors to frequently used chemotherapeutic agents, were prepared by a stereodivergent biotransformation and a biocatalytic kinetic resolution of the corresponding dibenzylbutyrolactones with the same 2-oxoglutarate-dependent dioxygenase. The reaction can be conducted on 2 g scale, and the enzyme allows tailoring of the initial, “natural” structure and thus transforms various non-natural derivatives. Depending on the substitution pattern, the enzyme performs an oxidative C?C bond formation by C?H activation or hydroxylation at the benzylic position prone to ring closure.
- Lazzarotto, Mattia,Hammerer, Lucas,Hetmann, Michael,Borg, Annika,Schmermund, Luca,Steiner, Lorenz,Hartmann, Peter,Belaj, Ferdinand,Kroutil, Wolfgang,Gruber, Karl,Fuchs, Michael
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p. 8226 - 8230
(2019/05/21)
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- Asymmetric Chemoenzymatic Synthesis of (?)-Podophyllotoxin and Related Aryltetralin Lignans
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(?)-Podophyllotoxin is one of the most potent microtubule depolymerizing agents and has served as an important lead compound in antineoplastic drug discovery. Reported here is a short chemoenzymatic total synthesis of (?)-podophyllotoxin and related aryltetralin lignans. Vital to this approach is the use of an enzymatic oxidative C?C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion. This strategy allows gram-scale access to (?)-deoxypodophyllotoxin and is readily adaptable to the preparation of related aryltetralin lignans.
- Li, Jian,Zhang, Xiao,Renata, Hans
-
p. 11657 - 11660
(2019/08/02)
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- Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis
-
A nickel-catalyzed reductive cascade approach to the efficient construction of diastereodivergent cores embedded in podophyllum lignans is developed for the first time. Their gram-scale access paved the way for unified syntheses of naturally occurring podophyllotoxin and other members.
- Xiao, Jian,Cong, Xiao-Wei,Yang, Gui-Zhen,Wang, Ya-Wen,Peng, Yu
-
supporting information
p. 1651 - 1654
(2018/03/23)
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- Synthesis and Computational Studies Demonstrate the Utility of an Intramolecular Styryl Diels-Alder Reaction and Di-t-butylhydroxytoluene Assisted [1,3]-Shift to Construct Anticancer dl-Deoxypodophyllotoxin
-
Deoxypodophyllotoxin is a secondary metabolite lignan possessing potent anticancer activity with potential as a precursor for known anticancer drugs, but its use is limited by scarcity from natural sources. We here report the total synthesis of racemic de
- Saavedra, Diana I.,Rencher, Benjamin D.,Kwon, Doo-Hyun,Smith, Stacey J.,Ess, Daniel H.,Andrus, Merritt B.
-
p. 2018 - 2026
(2018/02/23)
-
- Design and synthesis of novel 4'-demethyl-4-deoxypodophyllotoxin derivatives as potential anticancer agents
-
A group of podophyllotoxin (PPT) derivatives (7a-j) were synthesized by conjugating aryloxyacetanilide moieties to the 4'-hydroxyl of 4'-demethyl-4-deoxypodophyllotoxin (DDPT), and their anticancer activity was evaluated. It was found that the most potent compound 7d inhibited the proliferation of three cancer cell lines with sub to low micromolar IC50 values. Furthermore, it was demonstrated that 7d induced cell cycle arrest in G2/M phase in MGC-803 cells, and regulated the expression of cell cycle check point proteins, such as cyclin A, cyclin B, CDK1, cdc25c, and p21. Finally, 4 mg/kg of 7d reduced the weights and volumes of HepG2 xenografts in mice. Our findings suggest that 7d might be a potential anticancer agent.
- Zhu, Xiong,Fu, Junjie,Tang, Yan,Gao, Yuan,Zhang, Shijin,Guo, Qinglong
-
supporting information
p. 1360 - 1364
(2016/02/23)
-
- Synthesis and insecticidal activity of new deoxypodophyllotoxin derivatives modified in the D-ring
-
In continuation of our program aimed at the discovery of new natural-product-based insecticidal agents, twenty-six deoxypodophyllotoxin derivatives modified in the D-ring were synthesized and evaluated as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1 mg/mL. The configuration of three compounds 3, 4, and IIIi was unambiguously determined by single-crystal X-ray diffraction. It demonstrated that aminolysis of deoxypodophyllotoxin in the presence of pyrrolidine and piperidine could result in complete inversion of the configuration of the carbonyl group at its C-2 position. Five compounds IIa, IIi-k, and IIIh showed the equal or higher insecticidal activity than toosendanin. Especially IIj displayed the most potent insecticidal activity with the final mortality rate of 65.5%.
- Wang, Juanjuan,Yu, Xiang,Zhi, Xiaoyan,Xu, Hui
-
supporting information
p. 4542 - 4545
(2015/02/06)
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- Synthesis and insecticidal activity of new deoxypodophyllotoxin-based phenazine analogues against Mythimna separata walker
-
In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, a series of new deoxypodophyllotoxin- based phenazine analogues modified in their E-ring were prepared, and their structures were well characterized by 1H NMR, HRMS, ESI-MS, IR, optical rotation, and mp. The absolute steric configuration of one key isomer was unambiguously confirmed by X-ray crystallography. Their insecticidal activity was examined against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at the concentration of 1 mg/mL. All derivatives showed delayed insecticidal activity. Especially compound 9i, containing p-methoxybenzoylamnio at the C-9′ position of deoxypodophyllotoxin-based phenazine fragment, exhibited the most promising insecticidal activity with the final mortality rate of 72.4%. According to the symptoms of the tested M. separata, the derivatives likely displayed an antimolting hormone effect. In addition, preliminary structure-activity relationships were observed. These suggested that the proper length of the side chain of alkylacylamino might be important for their insecticidal activity, and introduction of the acylamino groups at the C-9′ position of deoxypodophyllotoxin-based phenazine fragment usually afforded more potent compounds than those containing the same ones at the C-10′ position. This will pave the way for further design, structural modification, and development of deoxypodophyllotoxin-based derivatives as insecticidal agents.
- Wang, Juanjuan,Zhi, Xiaoyan,Yu, Xiang,Xu, Hui
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p. 6336 - 6343
(2013/07/26)
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- Synthesis and antimitotic and tubulin interaction profiles of novel pinacol derivatives of podophyllotoxins
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Several pinacol derivatives of podophyllotoxins bearing different side chains and functions at C-7 were synthesized through reductive cross-coupling of podophyllotoxone and several aldehydes and ketones. While possessing a hydroxylated chain at C-7, the compounds retained their respective hydroxyl group with either the 7α (podo) or 7β (epipodo) configuration. Along with pinacols, some C-7 alkylidene and C-7 alkyl derivatives were also prepared. Cytotoxicities against neoplastic cells followed by cell cycle arrest and cellular microtubule disruption were evaluated and mechanistically characterized through tubulin polymerization inhibition and assays of binding to the colchicine site. Compounds of the epipodopinacol (7β-OH) series behaved similarly to podophyllotoxin in all the assays and proved to be the most potent inhibitors. Significantly, 7α-isopropyl-7-deoxypodophyllotoxin (20), without any hydroxyl function, appeared as a promising lead compound for a novel type of tubulin polymerization inhibitors. Experimental results were in overall agreement with modeling and docking studies performed on representative compounds of each series.
- Abad, Andrés,López-Pérez, José L.,Del Olmo, Esther,García-Fernández, Luis F.,Francesch, Andrés,Trigili, Chiara,Barasoain, Isabel,Andreu, José M.,Fernand Díaz,San Feliciano, Arturo
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experimental part
p. 6724 - 6737
(2012/09/25)
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- Synthesis and biological evaluation of derivatives of 4- deoxypodophyllotoxin as antitumor agents
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In an attempt to generate compounds with superior bioactivity and reduced toxicity, a series of derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin with substituted piperazines or their amino acid amides. The cytotoxic activity of these compounds against three human cancer cell lines was evaluated. We found that p- nitrophenylpiperazine substitution (Compound 8b) led to an increase in the potency of the compound. Compound 8b exhibited the most potent cytotoxicity against A-549, HeLa and SiHa cells (IC50 values were 0.102, 0.180 and 0.0195 μM, respectively). In addition, flow cytometric analysis showed that 8b induced cell cycle arrest in the G1 phase accompanied by apoptosis in A-549 cells.
- Jin, Yan,Liu, Jie,Huang, Wen-Ting,Chen, Shi-Wu,Hui, Ling
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experimental part
p. 4056 - 4061
(2011/11/12)
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- First synthesis and biological evaluation of novel spin-labeled derivatives of deoxypodophyllotoxin
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Deoxypodophyllotoxin inhibits tubulin polymerization and induces cell cycle arrest at G2/M, followed by apoptosis. In order to find compounds with superior bioactivity and less toxicity, a series of spin-labeled derivatives of deoxypodophyllotoxin were synthesized by reacting 4′-demethyl-4-deoxypodophyllotoxin (DPPT) with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyloxycarbonyl) amino acids. The cytotoxic activities against three tumor cell lines (HL-60, RPMI-8226, A-549) in vitro and the antioxidative activities in tissues of Sprague Dawley (SD) rats of target compounds were evaluated, and the results indicated that compounds 11a-h were more potent in terms of cytotoxicities and antioxidative activities than either parent compound DPPT or anticancer drug VP-16.
- Zhang, Zhi-Wei,Zhang, Jia-Qiang,Hui, Ling,Chen, Shi-Wu,Tian, Xuan
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experimental part
p. 1673 - 1677
(2010/05/18)
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- Natural products-based insecticidal agents 5. Design, semisynthesis and insecticidal activity of novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin against Mythimna separata Walker in vivo
-
In an attempt to find the effective phytopesticides, eight novel 4′-substituted benzenesulfonate derivatives of 4-deoxypodophyllotoxin were synthesized and preliminarily tested against the pre-third-instar larvae of Mythimna separata Walker in vivo at the concentration of 1 mg/mL. Among all of the tested analogs, compounds 5a, 5c, 5d, and 5h showed the higher insecticidal activity than 4-deoxypodophyllotoxin. Especially 5a exhibited the most potent insecticidal activity compared with toosendanin, a commercial insecticide derived from Melia azedarach.
- Xu, Hui,Wang, Juan-Juan
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experimental part
p. 2500 - 2502
(2010/07/16)
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- Semisynthesis and quantitative structure-activity relationship (QSAR) study of novel aromatic esters of 4-demethyl-4-deoxypodophyllotoxin as lnsecticidal agents
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By using podophyllotoxin as a phytoinsecticidal lead compound, 15 novel aromatic esters of 4'demethyl-4-deoxypodophyllotoxin were semisynthesized and preliminarily tested for their insecticidal activity against the pre-third-instar larvae of Mythimna separata Walker in vivo for the first time. Among all of the tested compounds, especially two compounds, 4m and 4o, containing a pyridinyl group, for which final corrected mortality rates against M. separata at 1 mg/mL were 62.9 and 59.2%, respectively, showed the most promising and pronounced insecticidal activity as compared with toosendanin, a commercial insecticide derived from Melia azedarach. The quantitative structure-activity relationships (QSAR) of compounds 4a-4o showed that the relative number of benzene rings and final heat of formation were very important descriptors to their insecticidal activity.
- Xu, Hui,Wang, Juanjuan,Sun, Huijun,Min, Lv,Tian, Xuan,Yau, Xiaojun,Zhang, Xing
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experimental part
p. 7919 - 7923
(2010/08/13)
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- ANTINEOPLASTIC COMPOUNDS
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A compound of general formula (I), wherein Ar, R1, R2, R3 and R4 take various meanings with the proviso that R2 and R3 are not both H, for use in the treatment of cancer.
- -
-
Page/Page column 15-17
(2008/06/13)
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- Radical-mediated synthesis of racemic deoxypodophyllotoxin and related lignans
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An approach for the synthesis of lignans related to the podophyllotoxin family is reported. The key reaction is a highly diastereoselective iodoacetal cyclization under iodine atom transfer conditions followed by a hornolytic aromatic substitution. The second aromatic ring is introduced at a later stage via addition of aryllithium to an aryl ketone. A novel and very mild method for the deoxygenation of the intermediate tertiary benzylic alcohols is described. Georg Thieme Verlag Stuttgart.
- Kolly-Kovac, Tanja,Renaud, Philippe
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p. 1459 - 1466
(2007/10/03)
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- Cytotoxic responses to aromatic ring and configurational variations in α-conidendrin, podophyllotoxin, and sikkimotoxin derivatives
-
Derivatives of α-conidendrin, podophyllotoxin, and sikkimotoxin were prepared to evaluate the cytotoxic contributions of C-4 configuration and pendant and fused arene substitutions. Dimethyl-α-conidendryl alcohol (5), 9-deoxypodophyllol (6), and 9-deoxysikkimol (17) were dehydrated to their respective oxolane derivatives 4, 3, and 9. Diols 5 and 6 were converted via oxabicyclo[3.2.1]octanols 10 and 14 to target oxolanes 8 and 7 where C-4 had been inverted relative to that in 3 and 4. Cytotoxicities of the five oxolanes were determined in two drug-sensitive human leukemia and two multidrug-resistant cell lines expressing P-glycoprotein or multidrug-resistance associated protein (MRP). Changing the pendant arene configuration or replacing a m-methoxy by hydrogen resulted in a 100-fold cytotoxicity loss. Replacing a methylenedioxy group in the fused arene by two methoxy substituents reduced cytotoxicity by 10-fold. Drug-resistant cell lines were equally resistant to compounds 3, 4, 8, and 9 indicating that these four compounds do not serve as substrates of the transport proteins P-glycoprotein and MRP.
- Dantzig,LaLonde,Ramdayal,Shepard,Yanai,Zhang
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p. 180 - 185
(2007/10/03)
-
- Carbon-13 NMR Chemical Shifts of some Podophyllum Lignans and Analogues
-
Carbon-13 nmr chemical shifts of a number of podophyllum lignans, podophyllotoxin, 4′-demethylpodophyllotoxin, podophyllotoxone, desoxypodophyllotoxin and their derivatives have been determined. The derivatives include 1-naphthol, quinone, diol and tetrahydrofuran compounds.
- Mitra, Jayati,Mitra, Alok Kumar
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p. 692 - 694
(2007/10/03)
-
- Total synthesis of isodeoxypodophyllotoxin using the Me3Sn radical initiated carbocyclization
-
The lactone portion of the podophylotoxin framework was assembled from a free-radical carbocyclization reaction, and the target structure was constructed based on intramolecular Friedel-Crafts reaction. In addition to isodeoxypodophyllotoxin, there were formed unusual tri- and tetracyclic compounds.The lactone portion of the podophylotoxin framework was assembled from a free-radical carbocyclization reaction, and the target structure was constructed based on intramolecular Friedel-Crafts reaction. In addition to isodeoxypodophyllotoxin, there were formed unusual tri- and tetracyclic compounds.
- Hanessian, Stephen,Ninkovic, Sacha
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p. 1880 - 1888
(2007/10/03)
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- Synthesis, antitumoral and antiviral evaluation of halo- and demethyl-yatein derivatives
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Several chloro- and iodo-lignanolides have been obtained by direct halogenation of aromatic rings from yatein and 4'-O-demethylyatein. They were assayed as antineoplastics, in order to check the influence in the activity of substitution in both aromatic rings. Although these compounds show a modest antineoplastic activity, it is far from that displayed by yatein and podophyllotoxin. These results confirm that demethylation and the introduction of halo substituents diminish the activity of lignans of the dibenzylbutyrolactone type.
- Medarde,Pelaez-Lamamie De Clairac,Luis Lopez,Gravalos,San Feliciano
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p. 640 - 644
(2007/10/03)
-
- Synthesis and cytotoxicity of novel lignans
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In this study the syntheses of 11 novel lignans are described. Their cytotoxicities are studied in GLC4, a human small cell lung carcinoma cell line, using the microculture tetrazolium (MTT) assay. Ten of these compounds were substituted with a menthyloxy group on the 5-position of the lactone. These compounds can easily be prepared in (novel) 'one-pot', three- or four- step syntheses. In addition, methods for controlling the stereogenic centers are described. Furthermore, five naturally occurring podophyllotoxin-related compounds were tested. The cytotoxicities of all lignan compounds, and of three non-lignan intermediates originating from the syntheses, were compared with the clinically applied anticancer agents etoposide, teniposide, and cisplatin. Most compounds showed moderate to high activities against GLC4, and two of the compounds containing a menthyloxy group showed activities comparable to the reference cytotoxic agents.
- Middel,Woerdenbag,Van Uden,Van Oeveren,Jansen,Feringa,Konings,Pras,Kellogg
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p. 2112 - 2118
(2007/10/02)
-
- An asymmetric synthesis of (-)-deoxypodophyllotoxin
-
A Diels-Alder cycloaddition between the fumarate of methyl (S)-mandelate (22) and α-hydroxy-α-aryl-o-quinodimethane 21 produces an endo cycloadduct (23) in 58% yield. The preparation of the precursor to o-quinodimethane 21 and the conversion of cycloadduct 23 to optically pure (-)-deoxypodophyllotoxin (1) is described.
- Bogucki,Charlton
-
p. 588 - 593
(2007/10/02)
-
- Synthesis of (+/-)-4-Deoxypodophyllotoxin, (+/-)-Podophyllotoxin and (+/-)-Epipodophyllotoxin
-
6,7-Methylenedioxy-1-(3',4',5'-trimethoxyphenyl)-2-benzopyran-3-one 1 and dimethyl fumarate in acetonitrile give mostly the C-2 exo-CO2Me adduct 4 which is transformed in four steps into epipodophyllotoxin 10a.Attempted addition of dimethyl maleate to 1 p
- Jones David W.,Thompson, Adrian M.
-
p. 2541 - 2548
(2007/10/02)
-
- Synthesis of non-phenolic bisbenzocyclooctadiene lignan lactones and aporphinic alkaloids, by oxidative coupling with new agents in fluoro acid medium. IV
-
A systematic study of oxidants used in fluoro acid medium allowed us to increase notably the number of efficient reagents for the non-phenolic oxidative coupling of lignan and alkaloid precursors. If dibenzylbutanolide had no methylenedioxyle group, Re2O7 and RuO2.2H2O were the most efficient. With a methylenedioxyle group, best results were obtained with Tl2O3, Mn(OAc)3.2H2O and Ce(OH)4. Finally, aporphines were obtained with good yields with Ce(OH)4, RuO2.2H2O and Fe(OH)(OAc)2.
- Planchenault,Dhal,Robin
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p. 5823 - 5830
(2007/10/02)
-
- Synthesis of podophyllotoxin derivatives by means of tributyltin hydride- or palladium-mediated cyclization of α-benzylidene-β-(o-bromobenzyl)-γ-lactones
-
Synthesis of podophyllotoxin derivatives based on an aryl radical cyclization of α-benzylidene-β-(o-bromobenzyl)-γ-lactones 20 and 21 has been examined. Treatment of a mixture of the alcohols 18a and 18b (ca. 1:1), prepared from 6-bromopiperonal (10) in 7 steps, with methanesulfonyl chloride gave a ca. 3:1 mixture of the chlorides 19a and 19b, which was treated with DBU to give the (Z)-and (E)-α-benzylidene-γ-lactones 20 and 21 in 64 and 22% yields, respectively. Thermolysis of the mixture of the sulfoxides 23a and 23b, prepared from 18a,b, afforded the E-isomer 21 as a major product. The Z-benzylidenelactone 20 when treated with Bu3SnH in the presence of AlBN gave the 6-endo-trig radical cyclization product, (±)-deoxyisopicropodophyllin (24), and the 5-exo-trig cyclization product 25 in 29 and 49% yields, respectively. The E-isomer 21, however, gave only the 5-exo cyclization product 25. On the other hand, treatment of 20 with PdCl2(PPh3)3 gave (±)-γ-apopicropodophyllin (29) in 75% yield. Similar treatment of 21 afforded no cyclization product, but, in the presence of sodium formate (H- source), gave the 5-exo cyclization product 25 in 84% yield.
- Ishibashi, Hiroyuki,Ito, Katsuhiro,Hirano, Tomiya,Tabuchi, Masayo,Ikeda, Masazumi
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p. 4173 - 4182
(2007/10/02)
-
- Efficient Asymmetric Syntheses of Naturally Occurring Lignan Lactones Using Catalytic Asymmetric Hydrogenation as a Key Reaction
-
Optically pure (R)-arylmethylsuccinic acid mono-methyl esters were obtained efficiently by using the catalytic asymmetric hydrogenation of arylidenesuccinic acid monoesters with a rhodium(I) complex of a chiral bisphosphine, (4S,5S)-MOD-DIOP.Asymmetric total syntheses of some naturally occurring lignans, (+)-collinusin, (-)-deoxypodophyllotoxin, and (+)-neoisostegane, were achieved via several steps from (R)-γ-butyrolactones as key intermediates obtained by reduction of (R)-arylmethylsuccinic acid mono methyl-esters.
- Morimoto, Toshiaki,Chiba, Mitsuo,Achiwa, Kazuo
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p. 1793 - 1806
(2007/10/02)
-
- SYNTHETIC STUDIES ON PODOPHYLLUM LIGNANS: TRIBUTYLTIN HYDRIDE-INDUCED RADICAL CYCLIZATION AND INTRAMOLECULAR HECK REACTION OF α-BENZYLIDENE-β-(o-BROMOBENZYL)-γ-LACTONES
-
Tributyltin hydride-induced radical cyclization of the (Z)-α-benzylidene-β-(o-bromobenzyl)-γ-lactone (16) gave the 6-endo cyclization product, (+/-)-deoxyisopicropodophyllin (18), and the 5-exo cyclization product (19).On the other hand, the intramolecular Heck reaction of 16 provided (+/-)-γ-apopicropodophyllin (20) as a sole cyclization product.
- Ishibashi, Hiroyuki,Ito, Katsuhiro,Tabuchi, Masayo,Ikeda, Masazumi
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p. 1279 - 1282
(2007/10/02)
-
- Asymmetric total synthesis of (-)-deoxypodophyllotoxin
-
An efficient total synthesis of (-)-deoxpophyllotoxin has been achieved by employing the asymmetric hydrogenation of α-piperonylidene-succinic acid half ester with a rhodium(I) complex of (S,S)-MOD-DIOP as a key step.
- Morimoto,Chiba,Achiwa
-
p. 261 - 264
(2007/10/02)
-
- 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
-
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.
- Brown, Eric,Daugan, Alain
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p. 141 - 154
(2007/10/02)
-
- Comprehensive Synthetic Route to Eight Diastereomeric Podophyllum Lignans
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An oxabicyclo compound, 9, prepared in 47percent yield through an isobenzofuran intermediate was converted with excellent regio- and stereocontrol to eight (+/-)-lignan lactones of the podophyllotoxin series.One of the eight, epiisopicropodophyllin, 36, t
- Forsey, Steven P.,Rajapaksa, Dayananda,Taylor, Nicholas J.,Rodrigo, Russell
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p. 4280 - 4290
(2007/10/02)
-
- Regioselective Suprafacial 1,5-Hydrogen Shifts in o-Quinodimethanes; a Route to 4-Deoxypodophyllotoxin
-
The o-quinodimethane intermediate (4a) with cis-CO2Me groups undergoes regioselective 1,5-hydrogen shift to the cis-dihydronaphthalene (5a) whilst its trans-isomer (9a) gives both 1,5-hydrogen shift products (6a) and (7a); (5a) is readily converted into 4
- Jones, David W.,Thompson, Adrian M.
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p. 1095 - 1096
(2007/10/02)
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- A SHORT VERSATILE SYNTHESIS OF ARYLTETRALIN LIGNANS INCLUDING DEOXYISOPODOPHYLLOTOXIN AND EPI-ISOPODOPHYLLOTOXIN
-
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).
- Pelter, Andrew,Ward, Robert S.,Pritchard, Martyn C.,Kay, I. Trevor
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p. 1615 - 1624
(2007/10/02)
-
- Oxidative Coupling of Lignans. III. Non-Phenolic Oxidative Coupling of Deoxypodorhizon and Related Compounds
-
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.
- Cambie, Richard C.,Craw, Peter A.,Rutledge, Peter S.,Woodgate, Paul D.
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p. 897 - 918
(2007/10/02)
-
- SYNTHESIS OF DEOXYISOPODOPHYLLOTOXIN AND EPIISOPODOPHYLLOTOXIN.
-
Cyclisation of the tandem conjugate addition products 1-3 by displacement of either the OH or SPh group provides a short efficient synthesis of lignan lactones including compounds of the clinically important podophyllotoxin series.
- Pelter, Andrew,Ward, Robert S.,Pritchard, Martyn C.,Kay, I. Trevor
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p. 6377 - 6380
(2007/10/02)
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- The Synthesis of Lignans and Related Structures using Quinodimethanes and Isobenzofurans: Approaches to the Podophyllins
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Novel routes to 1-aryl-5,6-dialkoxy-1,3-dihydrobenzothiophene 2,2-dioxides (13) and to the corresponding benzofuran (8) have been developed; these species yield quinodimethanes (12) via thermal extrusion of SO2 and isobenzofurans (5c) in an acid-cat
- Mann, John,Piper, Susan E.,Yeung, Lilan K.P.
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p. 2081 - 2088
(2007/10/02)
-
- Studies on the Constituents of the Seeds of Hernandia ovigera L. IV. Syntheses of β-Peltatin-A and -B Methyl Ethers from Desoxypodophyllotoxin
-
Two kinds of 4-aryltetralin type lignans, β-peltatin-A methyl ether (I-A) and β-peltatin-B methyl ether (I-B), were synthesized from desoxypodophyllotoxin (DPT), which is available in large quantities from the seeds of Hernandia ovigera L. (Hernandiaceae).The syntheses were achieved via demethylene-DPT (IV), 8-bromo-demethylene-DPT (V) and 8-bromo-DPT (VI).Methylenation of V was carried out successfully by using cesium fluoride and methylene iodide in DMF.Compound I-B was readily obtained by the reaction of VI with cuprous iodide and sodium methoxide in the presence of pyridine.Synthesis of I-A was only achieved by the reaction of lithiated VI with nitrobenzene at -100 deg C in the presence of tetramethylethylene diamine, and I-A was obtained in low yield, together with I-B.Keywords Hernandia ovigera; 4-aryltetralin lignan; desoxypodophyllotoxin (DPT); desoxypicropodophyllin (DPP); 2'-bromo-desoxypodophyllotoxin; 8-bromo-desoxypodophyllotoxin; beta-peltatin-A methyl ether; beta-peltatin-B methyl ether; lithiated desoxypodophyllotoxin; lignan X-ray analysis
- Yamaguchi, Hideo,Nakajima, Syunji,Arimoto, Masao,Tanoguchi, Mariko,Ishida, Toshimasa,Inoue, Masatoshi
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p. 1754 - 1760
(2007/10/02)
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- 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
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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
- Robin, Jean-Pierre,Dhal, Robert,Brown, Eric
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p. 3667 - 3671
(2007/10/02)
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- The Preparation of Lignans via Intermolecular Cycloadditions with Quinodimethanes
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Certain lignans can be prepared using, as the key step, a thermal reaction between 1-(aryl)-1,3-dihydro-5,6-dialkoxy-benzothiophen 2,2-dioxides and dienophiles.
- Mann, John,Piper, Susan E.
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p. 430 - 432
(2007/10/02)
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- A Stereo- and Regiocontrolled Synthesis of Podophyllum Lignans
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A Diels-Alder adduct of an isobenzofuran (generated in situ) and dimethyl acetylenedicarboxylate is converted by a series of controlled reductions and isomerizations to the lignans deoxy- and isodeoxypodophyllotoxin in seven stages.
- Rodrigo, Russell
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p. 4538 - 4540
(2007/10/02)
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