Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis

Xiao, Jian; Cong, Xiao-Wei; Yang, Gui-Zhen; Wang, Yawen; Peng, Yu

doi:10.1021/acs.orglett.8b00408

Cited by 62 publications

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References 62 publications

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“…[24] [f ]The experiment was conducted on 50 mg substrate scale. b) Preparationo fsubstrate rac-2b:i nstallation of the "natural" stereoconfiguration.…”

mentioning

confidence: 99%

“…Thet ransformation of substrate rac-2b with the biocatalyst turned out to be enantioselective,l eading to ak inetic [24] [f ]The experiment was conducted on 50 mg substrate scale. Bold and dashed lines refer to relative stereochemistry;b old and dashed wedges refer to absolute stereochemistry.…”

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confidence: 99%

“…Thel actone moiety and the southern aromatic fragment are required for high enzyme activity.T he northern hydroxy function can be removed, resulting in alterations of the [a] Yield [b] ee [d] Yield [b] ee [c] 11 mg 50 - [ [24] [a] The conversion was determined from calibrated HPLC-UV spectra.…”

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confidence: 99%

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Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

et al. 2019

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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.

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“…[24] [f ]The experiment was conducted on 50 mg substrate scale. b) Preparationo fsubstrate rac-2b:i nstallation of the "natural" stereoconfiguration.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

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Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

et al. 2019

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“…[24] [f ]Experimentwurde als 50 mg Substrat-Ansatz durchgeführt.Fette und gestrichelte Linien beziehen sich auf die relative Stereochemie, fette und gestrichelte Keile beziehen sich auf die absoluteS tereochemie. Wirk onnten 770 mg (39 %A usbeute) des gewünschten Produktes 11 d aus 235 mL Reaktionsgemisch innerhalb von 18 hg ewinnen.…”

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“…Das neue chirale Zentrum, welches während der C-C-Bindungsbildung entsteht, besitzt aber in beiden aus den Substratenantiomeren gebildeten Produkten die gleiche Konfiguration (zwei Diastereomere entstehen D 20 -Werte für 11 a und 3 stimmen mit den in der Literatur angegebenen Werten überein. [24] [f ]Experimentwurde als 50 mg Substrat-Ansatz durchgeführt.Fette und gestrichelte Linien beziehen sich auf die relative Stereochemie, fette und gestrichelte Keile beziehen sich auf die absoluteS tereochemie. [25] [e] Ausbeute wurde nicht bestimmt.…”

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Chemoenzymatische Totalsynthese von Deoxy‐, epi‐ und Podophyllotoxin sowie biokatalytische kinetische Racematspaltung von Dibenzylbutyrolactonen

et al. 2019

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Podophyllotoxin (1)i st einer der bekanntesten Vertreter von natürlich vorkommenden Lignanen. Deoxy-, epiund Podophyllotoxin, welche alle Vorstufen fürh äufig verwendete chemotherapeutische Verbindungen darstellen, wurden mithilfe einer stereodivergenten Biotransformation und biokatalytischen kinetischen Racematspaltung der jeweiligen Dibenzylbutyrolactone durch dieselbe 2-Oxoglutaratabhängige Dioxygenase( 2-ODD) hergestellt. Zudem konnte gezeigt werden, dass ein "Upscaling" der Reaktion auf 2g mçglich ist, sowied ass das 2-ODD-Enzym Modifikationen des "natürlichen" Substrates toleriert und somit verschiedenste nichtnatürlicheD erivate umsetzen kann. Das Enzym führt je nachS ubstituentenmuster entweder eine oxidative C-C-Bindungsbildung durch C-H-Aktivierung oder Hydroxylierung an der fürdie Ringschließung zugänglichen benzylischen Position durch.

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Nickel‐Catalyzed Asymmetric Reductive Arylalkylation of Unactivated Alkenes

Jin

Wang

2019

Angewandte Chemie

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Reported is an asymmetric reductive dicarbofunctionalization of unactivated alkenes. Under the catalysis of a Ni/BOX system, various aryl bromides, incorporating a pendant olefinic unit, were successfully reacted with an array of primary alkyl bromides in the presence of Zn as a reductant, furnishing a series of benzene‐fused cyclic compounds bearing a quaternary stereocenter in high enantioselectivities. Notably, this reaction avoids the use of pregenerated organometallics and demonstrates high tolerance of sensitive functionalities. The preliminary mechanistic investigations reveal that this Ni‐catalyzed reaction proceeds as a cascade consisting of migratory insertion and cross‐coupling with a nickel(I)‐mediated intramolecular 5‐exo cyclization as the enantiodetermining step.

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Divergent Asymmetric Syntheses of Podophyllotoxin and Related Family Members via Stereoselective Reductive Ni-Catalysis

Abstract: 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.

Cited by 62 publications

References 62 publications

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

Chemoenzymatic Total Synthesis of Deoxy‐, epi‐, and Podophyllotoxin and a Biocatalytic Kinetic Resolution of Dibenzylbutyrolactones

Chemoenzymatische Totalsynthese von Deoxy‐, epi‐ und Podophyllotoxin sowie biokatalytische kinetische Racematspaltung von Dibenzylbutyrolactonen

Nickel‐Catalyzed Asymmetric Reductive Arylalkylation of Unactivated Alkenes

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