Formal synthesis of (-)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester--a flow photochemistry approach.

  title={Formal synthesis of (-)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester--a flow photochemistry approach.},
  author={Kamil Lisiecki and Krzysztof K. Krawczyk and Piotr I. Roszkowski and Jan K Maurin and Zbigniew Czarnocki},
  journal={Organic \& biomolecular chemistry},
  volume={14 2},
We have developed a strategy for the stereoselective synthesis of cyclolignans related to podophyllotoxin and its derivatives. The crucial step of the synthesis is the photocyclization of a chiral atropoisomeric 1,2-bisbenzylidenesuccinate amide ester, which can be prepared from suitable aromatic aldehydes, diethyl succinate and l-prolinol. The photocyclization was found to be more efficient when irradiation was performed in a home-built continuous flow photochemical reactor. The in-flow… 
Unexpected regioselectivity in the photocyclization of a chiral 2,3-bisbenzylidenesuccinate, leading to a podophyllotoxin related cyclolignan
Abstract The Stobbe condensation between 3′,4′,5′-trimethoxyacetophenone and a benzylidenesuccinate derived from piperonal gave the Z,E-2,3-bisbenzylidenesuccinate as the only product. Such
Unusual visible-light photolytic cleavage of tertiary amides during the synthesis of cyclolignans related to podophyllotoxin
Abstract During the attempted photochemical cyclization of 2,3-bisbenzylidene-γ-hydroxybutyric acid cyclic amide ester, it was observed that a γ-butyrolactone ring was formed, which was concurrent
Asymmetric Chemoenzymatic Synthesis of (-)-Podophyllotoxin and Related Aryltetralin Lignans.
A short chemoenzymatic total synthesis of (-)-podophyllotoxin and related aryltetralin lignans is reported, using an enzymatic oxidative C-C coupling reaction to construct the tetracyclic core of the natural product in a diastereoselective fashion.
Total synthesis of podophyllotoxin and select analog designs via C–H activation
Abstract 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
Recent advances in the application of Diels-Alder reactions involving o-quinodimethanes, aza-o-quinone methides and o-quinone methides in natural product total synthesis.
This review summarizes recent advances in Diels-Alder reactions involving in situ-generated o-QDMs, o- QMs and aza-o-QMs, highlighting the power and potential of this strategy in organic synthesis and natural product total synthesis.
Advances in the Synthesis of Aryltetralin and Arylnaphthalene Lignans using Photocyclization
Lignans are a well-known and widely distributed class of natural products with huge structural and biological diversity. They occur in many species of plants, at different levels of content, in each
Recent strategies and tactics for the enantioselective total syntheses of cyclolignan natural products.
This review specifically addresses the cyclolignan subclass of the family, which possess both a C8-C8' and a C2-C7' linkage between two different phenylpropene units.
Domino Wittig-Diels Alder reaction: Synthesis of carbazole lignans
A convenient two step protocol for the synthesis of carbazole lignans involving Domino Wittig reaction/Diels Alder reaction followed by aromatization with DDQ is described. The main step of this
Advances in the Synthesis of Lignan Natural Products
Advances in the synthesis of lignan natural products in the last decade are outlined, including antibacterial, antiviral, antitumor, antiplatelet, phosphodiesterase inhibition, 5-lipoxygenase inhibition and HIV reverse transcription inhibition.
Novel podophyllotoxin and benzothiazole derivative induces transitional morphological and functional changes in HaCaT cells.
The KL3 derivative of PPT in contrast to PPT allows repair of normal keratinocytes and triggers mechanisms that restore non-tumor cell homeostasis and shows that KL3 is less toxic than PPT to non-cancerous cells.


Enantioselective formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate.
Meyers' 4-aryl-1-tetralone-lactone and ent-Zhang's 2-diarylmethyl-4-oxobutanoate were synthesized in the formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate, via
A short asymmetric synthesis of (+)-lyoniresinol dimethyl ether.
A short, efficient synthesis of the lignan (+)-lyoniresinol dimethyl ether is described, and the final product was recrystallized to constant melting point and rotation.
l-Prolinol as a chiral auxiliary in the photochemical synthesis of a new aryltetraline lignan analogue
Abstract Prochiral (E,E)-fulgide 8 was reacted with l -prolinol to afford cyclic (M)-fulgamide 10 in a two step reaction sequence. The UV-light-driven photocyclization of 10 proceeded
Synthesis of podophyllotoxin
The alkene (2) obtained directly from the reaction of dimethyl maleate with the pyrone (1) is converted into (±)-podophyllotoxin (12) in seven steps and 24% overall yield; novel steps include the
C-H bond arylation in the synthesis of aryltetralin lignans: a short total synthesis of podophyllotoxin.
A short total synthesis of podophyllotoxin, the prototypical aryltetralin lignan natural product, is reported, which 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.
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
Acid-catalyzed cyclization of 2,3-dibenzylidenesuccinates: synthesis of lignans (+/-)-cagayanin and (+/-)-galbulin.
Acid-catalyzed cyclizations of E,E-dibenzylidenesuccinate esters have been developed as an efficient synthetic route to 1-aryl-1,2-dihydronaphthalenes. This reaction has been used in the synthesis of
A practical in situ generation of the Schwartz reagent. Reduction of tertiary amides to aldehydes and hydrozirconation.
A new, highly efficient in situ protocol (Cp2ZrCl2/LiAlH(OBu-t)3) is described for the generation of the Schwartz reagent which provides a convenient method for the amide to aldehyde reduction and
Overcrowded molecules. Part VII. Thermal and photochemical reactions of photochromic (E)- and (Z)-benzylidene(diphenylmethylene)-succinic anhydrides and imides
The photochromic (E)- and (Z)-benzylidene(diphenylmethylene)succinic anhydrides and imides undergo reversible photochemical conrotatory ring closure reactions to form 1,8a-dihydronaphthalene
Advances in the Synthesis of Aryltetralin Lignan Lactones
Etoposide and tenoposide, derivatives of the aryltetralin lignan lactone podophyllotoxin (5), are clinically important anticancer agents. The structure of podophyllotoxin includes four contiguous