- Synthesis and In Vitro Anticancer Activity of Triazolyl Analogs of Podophyllotoxin, a Naturally Occurring Lignin
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Abstract: A series of triazolyl-modified podophyllotoxin analogs have been designed and synthesized by utilizing Huisgen 1,3-dipolar cycloaddition in order to develop potent antitumor agents. The synthesized analogs were assessed for in vitro anticancer a
- Ara, T.,Banday, J. A.,Bhat, B. A.,Ganaie, B. A.
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p. 2039 - 2047
(2022/01/24)
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- Scalable Aerobic Oxidation of Alcohols Using Catalytic DDQ/HNO3
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A selective, practical, and scalable aerobic oxidation of alcohols is described that uses catalytic amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and HNO3, with molecular oxygen serving as the terminal oxidant. The method was successfully applied to the oxidation of a wide range of benzylic, propargylic, and allylic alcohols, including two natural products, namely, carveol and podophyllotoxin. The conditions are also applicable to the selective oxidative deprotection of p-methoxybenzyl ethers.
- Arseniyadis, Stellios,Clavier, Louis,Copin, Chloé,Fournier, Jean,Giffard, Jean-Fran?ois,Jean, Alexandre,Katsina, Tania,Macedo Portela Da Silva, Nayane,Tamion, Rodolphe
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supporting information
p. 856 - 860
(2020/07/14)
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- Base-free oxidation of alcohols enabled by nickel(ii)-catalyzed transfer dehydrogenation
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An efficient nickel(ii)-catalyzed transfer dehydrogenation oxidation of alcohols is reported that relies on cyclohexanone as the formal oxidant and does not require the use of an external base. The synthetic utility of this protocol is demonstratedviathe facile oxidation of structurally complicated natural products.
- Ye, Danfeng,Liu, Zhiyuan,Sessler, Jonathan L.,Lei, Chuanhu
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supporting information
p. 11811 - 11814
(2020/10/13)
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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
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supporting information
p. 11657 - 11660
(2019/08/02)
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- Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
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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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supporting information
p. 8226 - 8230
(2019/05/21)
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- Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis
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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
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p. 1651 - 1654
(2018/03/23)
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- HAPTENS, HAPTEN CONJUGATES, COMPOSITIONS THEREOF AND METHOD FOR THEIR PREPARATION AND USE
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A method for performing a multiplexed diagnostic assay, such as for two or more different targets in a sample, is described. One embodiment comprised contacting the sample with two or more specific binding moieties that bind specifically to two or more di
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Paragraph 0234; 0235
(2016/07/27)
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- Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors
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A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50values in the range of 0.01-2.1 μM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.
- Kamal, Ahmed,Srinivasa Reddy,Polepalli, Sowjanya,Shalini, Nekkanti,Reddy, V. Ganga,Subba Rao,Jain, Nishant,Shankaraiah, Nagula
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p. 5466 - 5475
(2015/02/02)
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- Synthesis and insecticidal activity of novel hydrazone compounds derived from a naturally occurring lignan podophyllotoxin against Mythimna separata (Walker)
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In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, a series of novel hydrazone derivatives of podophyllotoxin, which is a naturally occurring aryltetralin lignan and isolated as the main secondary metabolite from the roots and rhizomes of Podophyllum species, 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. Especially compounds 8i, 8j, 8t, and 8u showed the more potent insecticidal activity with the final mortality rates greater than 60%.
- Wang, Yi,Yu, Xiang,Zhi, Xiaoyan,Xiao, Xiao,Yang, Chun,Xu, Hui
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p. 2621 - 2624
(2014/06/09)
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- Synthesis and quantitative structure-activity relationship (QSAR) study of novel isoxazoline and oxime derivatives of podophyllotoxin as insecticidal agents
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In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, 33 isoxazoline and oxime derivatives of podophyllotoxin modified in the C and D rings were synthesized and their structures were characterized by Proton nuclear magnetic resonance ( 1H NMR), high-resolution mass spectrometry (HRMS), electrospray ionization-mass spectrometry (ESI-MS), optical rotation, melting point (mp), and infrared (IR) spectroscopy. The stereochemical configurations of compounds 5e, 5f, and 9f were unambiguously determined by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of northern armyworm, Mythimna separata (Walker), in vivo. Compounds 5e, 9c, 11g, and 11h especially exhibited more promising insecticidal activity than toosendanin, a commercial botanical insecticide extracted from Melia azedarach. A genetic algorithm combined with multiple linear regression (GA-MLR) calculation is performed by the MOBY DIGS package. Five selected descriptors are as follows: one two-dimensional (2D) autocorrelation descriptor (GATS4e), one edge adjacency indice (EEig06x), one RDF descriptor (RDF080v), one three-dimensional (3D) MoRSE descriptor (Mor09v), and one atom-centered fragment (H-052) descriptor. Quantitative structure-activity relationship studies demonstrated that the insecticidal activity of these compounds was mainly influenced by many factors, such as electronic distribution, steric factors, etc. For this model, the standard deviation error in prediction (SDEP) is 0.0592, the correlation coefficient (R2) is 0.861, and the leave-one-out cross-validation correlation coefficient (Q2 loo) is 0.797.
- Wang, Yi,Shao, Yonghua,Wang, Yangyang,Fan, Lingling,Yu, Xiang,Zhi, Xiaoyan,Yang, Chun,Qu, Huan,Yao, Xiaojun,Xu, Hui
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p. 8435 - 8443
(2012/10/29)
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- Concise stereoselective synthesis of (-)-podophyllotoxin by an intermolecular iron(III)-catalyzed Friedel-Crafts alkylation
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(Chemical Equation Presented) Without further ado, the building blocks 1-3 were combined in three C-C bond-forming reactions to provide the enantiomerically pure natural product (-)-podophyllotoxin (4). The stereogenic center at C1 was generated in the key reaction, a diastereoselective iron(III)-catalyzed intermolecular Friedel-Crafts alkylation.
- Stadler, Daniel,Bach, Thorsten
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supporting information; body text
p. 7557 - 7559
(2009/03/12)
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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.
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Page/Page column 12; 14-15
(2008/06/13)
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- Correct structures of Diels-Alder adducts from the natural cyclolignan thuriferic acid and its 8-epimer
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A detailed analysis of one- and two-dimensional 1H and 13C NMR data for the endo and the exo adducts, obtained by Diels-Alder reaction of thuriferic and epithuriferic acids with cyclopentadiene is described. The unequivocal spectral
- López-Pérez, José L.,Abad, Andrés,Del Olmo, Esther,Feliciano, Arturo San
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p. 2370 - 2379
(2007/10/03)
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- 1-Aryltetralin privileged structure-based libraries: parallel synthesis of N-aryl and N-biaryl γ-lactam lignans
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The parallel solution-phase synthesis of two libraries of product-like compounds derived from a 1-aryltetralin privileged structure is described. The N-aryl picropodophyllone γ-lactams were synthesized from methyl ester thuriferic acid via InCl3/sub
- Dorbec, Matthieu,Florent, Jean-Claude,Monneret, Claude,Rager, Marie-No?lle,Bertounesque, Emmanuel
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p. 11766 - 11781
(2007/10/03)
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- Mild and selective oxidation of alcohols to aldehydes and ketones using NaIO4/TEMPO/NaBr system under acidic conditions
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A TEMPO-catalyzed selective oxidation of alcohols to the corresponding aldehydes and ketones using NaIO4 as the terminal oxidant is reported. The NaIO4/TEMPO/NaBr system provides a mild and efficient method for the oxidation of alcohols that are sensitive to basic conditions. Furthermore, the recoverable ionic liquid immobilized TEMPO-catalyzed oxidation of benzyl alcohol in ionic liquid-H2O medium is also developed.
- Lei, Ming,Hu, Rui-Jun,Wang, Yan-Guang
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p. 8928 - 8932
(2007/10/03)
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- Methyltrioxorhenium catalysed synthesis of highly oxidised aryltetralin lignans with anti-topoisomerase II and apoptogenic activities
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A novel and efficient procedure to prepare highly oxidised aryltetralin lignans, such as isopodophyllotoxone and (-)-aristologone derivatives, by oxidation of podophyllotoxin and galbulin with methylrhenium trioxide (MTO) and novel MTO heterogeneous catal
- Saladino, Raffaele,Fiani, Cinzia,Belfiore, Maria Cristina,Gualandi, Giampiero,Penna, Sabrina,Mosesso, Pasquale
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p. 5949 - 5960
(2007/10/03)
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- CONVERSION
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The present invention provides a process for the in vitro conversion of deoxypodophyllotoxin to podophyllotoxin. In vitro conversion of deoxypodophyllotoxin to podophyllotoxin is carried out by direct oxidation at the 7-position, full oxidation at the 7-p
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- The intramolecular carboxyarylation approach to podophyllotoxin
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Since 1960, only seven plant-derived anticancer drugs have received FDA approval for commercial production. Two are semisynthetic derivatives of podophyllotoxin. This paper describes concise, highly convergent, and conceptually novel approaches to (-)-pod
- Reynolds, Aaron J.,Scott, Andrew J.,Turner, Craig I.,Sherburn, Michael S.
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p. 12108 - 12109
(2007/10/03)
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- Cytotoxic cyclolignans related to podophyllotoxin
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The cyclolignan family of natural products includes compounds with important antineoplastic and antiviral properties such as podophyllotoxin and two of their semisynthetic derivatives, etoposide and teniposide. The latter are included in a wide variety of
- Gordaliza, Marina,Miguel Del Corral, Jose M.,Angeles Castro,Garcia-Garcia, Pablo A.,San Feliciano, Arturo
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p. 297 - 304
(2007/10/03)
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- Novel D-ring analogues of podophyllotoxin as potent anti-cancer agents
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Several D-ring modified analogues of podophyllotoxin were prepared viz semi-synthesis starting from naturally occuring podophyllotoxin and determined their in vitro anti-cancer activity. Most of the analogues have shown good activity towards human cancer cell lines.
- Subrahmanyam, Duvvuri,Renuka,Rao, C.V. Laxmana,Sagar, P. Sangeeta,Deevi, Dhanvanthri S.,Babu, J. Moses,Vyas
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p. 1391 - 1396
(2007/10/03)
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- A novel enzymatic dehydrogenation of podophyllotoxin congeners by yeast cells
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The biotransformation of aryltetralin lignans to arylnaphthalene lignans in presence of yeast is described. Podophyllotoxone, an oxidation product of podophyllotoxin on incubation with yeast from different sources produced dehydropodophyllotoxin, an important representative of arylnaphthalene lignans.
- Kamal, Ahmed,Damayanthi
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p. 657 - 662
(2007/10/03)
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- Carbon-13 NMR Chemical Shifts of some Podophyllum Lignans and Analogues
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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)
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- Immunosuppressive cyclolignans
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The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'- demethyldeoxypodophyllotoxin (8), β-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.
- Gordaliza, Marina,Faircloth, Glynn T.,Castro, Ma. Angeles,Miguel Del Corral, José M.,López-Vázquez, Ma. Luisa,San Feliciano, Arturo
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p. 2865 - 2868
(2007/10/03)
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- A new approach to the synthesis of podophyllotoxin based on epimerization reactions
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A formal synthesis of podophyllotoxin has been achieved by means of the well known conjugate addition-alkylation of 5H-furan-2-one, followed by cyclization and controlled epimerizations. This approach represents a useful new route to the 8,7'-trans-stereo
- Medarde, Manuel,Ramos, Angel C.,Caballero, Esther,Lopez, Jose Luis,Pelaez-Lamamie De Clairac, Rafael,San Feliciano, Arturo
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p. 2663 - 2666
(2007/10/03)
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- Reassignment of the configuration of several keto-cyclolignans prepared from podophyllotoxin
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The configuration of several keto-cyclolignans related to podophyllotoxin has been reviewed. Under basic catalysis, the configuration at the C-atom in α-position to the lactone carbonyl group in podophyllotoxone is inverted instead of the C-atom in α- pos
- Del Corral,Gordaliza,Lopez,Del Olmo,Castro,Lopez
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p. 1793 - 1796
(2007/10/02)
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- UNAMBIGUOUS CONFIGURATIONAL AND CONFORMATIONAL DETERMINATION OF THURIFERIC ACID
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The stereochemistry of thuriferic acid has been checked on the basis of spectral, chemical and molecular modelling findings.Under basic catalysis, the carbon alfa to the lactone carbonyl group in podophyllotoxone must be inverted instead of the carbon alf
- Lopez-Perez, Jose L.,Olmo, Ester del,Pascual-Teresa, Beatriz de,Merino, Marta,Martin, Sara,Feliciano, Arturo San
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p. 6343 - 6348
(2007/10/02)
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- A novel rearrangement product of podophyllotoxone - ester derivatives and in vitro cytotoxicity studies
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A new rearrangement product of podophyllotoxone was obtained by reaction with strong bases. In vitro cytotoxicities of this substance and some derivatives were determined using L-1210 and KB cell lines.
- Hofert,Matusch
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p. 771 - 777
(2007/10/02)
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- BIOTRANSFORMATION OF PODOPHYLLUM LIGNANS IN CELL SUSPENSION CULTURES OF FORSYTHIA INTERMEDIA
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Biotransformation studies using cell suspension cultures of Forsythia intermedia showed these are capable of rapidly oxidizing the aryltetralin lactone lignan podophyllotoxin into podophyllotoxone.Smaller amounts of the stereoisomer picropodophyllone were
- Broomhead, A. Jane,Dewick, Paul M.
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p. 1511 - 1517
(2007/10/02)
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- ACIDIC AND PHENOLIC LIGNANS FROM JUNIPERUS SABINA
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Key Word Index - Juniperus sabina; Cupressaceae; leaves; lignans; junaphtoic acid; (-)-3-O-demethylyatein.Along with some known compounds, two new lignans, a naphthalene derivative named junaphtoic acid and (-)-3-O-demethylyatein, were isolated from the a
- Feliciano, Arturo San,Corral, Jose M. Miguel Del,Gordaliza, Marina,Castro, Angeles
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p. 3483 - 3485
(2007/10/02)
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- Studies on the Constituents of the Seeds of Hernandia ovigera L. V. Syntheses of Epipodophyllotoxin and Podophyllotoxin from Desoxypodophyllotoxin
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Epipodophyllotoxin (EPT) and podophyllotoxin (PT) were prepared from desoxypodophyllotoxin (DPT), obtained from the seeds of Hernandia ovigera L. (Hernandiaceae).EPT was obtained together with dehydrodesoxypodophyllotoxin (I) by a radical bromination of D
- Yamaguchi, Hideo,Arimoto, Masao,Nakajima, Syunji,Tanoguchi, Mariko,Fukada, Yoshinari
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p. 2056 - 2060
(2007/10/02)
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- CYTOTOXIC LIGNANS FROM PODOPHYLLUM, AND THE NOMENCLATURE OF ARYLTETRALIN LIGNANS
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Roots of Podophyllum hexandrum and P. peltatum both contain (1R,2R,3R)-desoxypodophyllotoxin and the previously unreported (1R,2R,3R)-podophyllotoxone .Thermal isomerization of (1α,2α,3β)-pod
- Dewick, Paul M.,Jackson, David E.
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p. 2277 - 2280
(2007/10/02)
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