518-28-5Relevant articles and documents
Asymmetric total synthesis of (-)podophyllotoxin
Hadimani, Shreeshailkumar B.,Tanpure, Rajendra P.,Bhat, Sujata V.
, p. 4791 - 4794 (1996)
Asymmetric synthesis of podophyllotoxin is achieved through tandem conjugate addition of S (-) benzyl phenyl sulfoxide to but-2-en-4-olide.
Asymmetric Chemoenzymatic Synthesis of (?)-Podophyllotoxin and Related Aryltetralin Lignans
Li, Jian,Zhang, Xiao,Renata, Hans
, p. 11657 - 11660 (2019/08/02)
(?)-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.
Total synthesis of podophyllotoxin and select analog designs via C–H activation
Ting, Chi P.,Tschanen, Esther,Jang, Esther,Maimone, Thomas J.
, p. 3299 - 3308 (2019/05/15)
An account of our previously disclosed total synthesis of the aryltetralin lignan natural product podophyllotoxin, a building block used in the synthesis of the FDA-approved anticancer drug etoposide, is disclosed. A C–H activation disconnection was viewed as being amenable to the preparation of E-ring modified analogs but proved challenging to execute. Various insights into palladium-catalyzed C–H arylation reactions on complex scaffolds are reported ultimately leading to the implementation of this strategy and the synthesis of compounds inaccessible by semisynthetic means.
Chemoenzymatic Total Synthesis of Deoxy-, epi-, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones
Lazzarotto, Mattia,Hammerer, Lucas,Hetmann, Michael,Borg, Annika,Schmermund, Luca,Steiner, Lorenz,Hartmann, Peter,Belaj, Ferdinand,Kroutil, Wolfgang,Gruber, Karl,Fuchs, Michael
, p. 8226 - 8230 (2019/05/21)
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.
Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis
Xiao, Jian,Cong, Xiao-Wei,Yang, Gui-Zhen,Wang, Ya-Wen,Peng, Yu
, p. 1651 - 1654 (2018/03/23)
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.
Catalytic Enantioselective Synthesis of (-)-Podophyllotoxin
Hajra, Saumen,Garai, Sujay,Hazra, Sunit
, p. 6530 - 6533 (2017/12/26)
The first catalytic enantioselective total synthesis of (-)-podophyllotoxin is accomplished by a challenging organocatalytic cross-aldol Heck cyclization and distal stereocontrolled transfer hydrogenation in five steps from three aldehydes. Reversal of se
Ci-H bond arylation in the synthesis of aryltetralin lignans: A short total synthesis of podophyllotoxin
Ting, Chi P.,Maimone, Thomas J.
, p. 3115 - 3119 (2014/04/03)
A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported. Key to the success of this synthetic pathway is a Pd-catalyzed C(sp3)-H arylation reaction enabled by a conformational biasing element to promote C-C reductive elimination over an alternative Ci-N bond-forming pathway. This strategy allows for access to the natural product in five steps from commercially available bromopiperonal, and sheds light on subtle conformational effects governing reductive elimination pathways from high-valent palladium centers. Testing a new tactic: In a concise synthesis of podophyllotoxin with a crucial palladium-catalyzed arylation step, subtle conformational effects govern reductive elimination pathways from the high-valent palladium center. This route to aryltetralin lignan derivatives may be of interest in drug discovery.
Synthesis and antimitotic and tubulin interaction profiles of novel pinacol derivatives of podophyllotoxins
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
experimental part, p. 6724 - 6737 (2012/09/25)
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.
Concise stereoselective synthesis of (-)-podophyllotoxin by an intermolecular iron(III)-catalyzed Friedel-Crafts alkylation
Stadler, Daniel,Bach, Thorsten
supporting information; body text, p. 7557 - 7559 (2009/03/12)
(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.
Silenes in organic synthesis: A concise synthesis of (±)-epi- picropodophyllin
Pullin, Robert D. C.,Sellars, Jonathan D.,Steel, Patrick G.
, p. 3201 - 3206 (2008/04/01)
A concise, seven step synthesis of the aryl tetralin lignan lactone epi-picropodophyllin from piperonal is described. The key steps are a silene diene Diels-Alder reaction and the Hosomi-Sakurai reaction of the resultant silacyclohexene. The Royal Society
