Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono–Mannich Reaction

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(13), P. 7278 - 7287

Published: March 23, 2023

Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, class natural products that have been shown to elicit an array biological responses including modulating protein–protein interactions in human cancer cells. Our synthesis strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations install requisite all-carbon quaternary centers found each two monomeric products, aspidospermidine and eburnamine. Initial studies employing Suzuki–Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for structural reassignment product. final synthetic sequence employs Petasis borono–Mannich reaction couple eburnamine trifluoroborate derivative. These convergent approaches enabled eight diastereomers this heterodimer offer support absolute configuration strempeliopidine.

Language: Английский

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Catalytic enantioselective nitrone cycloadditions enabling collective syntheses of indole alkaloids

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 31, 2024

Abstract Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis tetrahydro-β-carboline have immense impacts attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types tetrahydro-β-carbolines bearing continuous multi-chiral centers quaternary centers. The method displays different endo/exo selectivity from traditional chemistry. distinct power this strategy has been illustrated by application collective enantiodivergent total syntheses 40 tetrahydro-β-carboline-type with divergent stereochemistry varied architectures.

Language: Английский

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Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 226 - 233

Published: Jan. 28, 2025

The integration of copper(I)-catalyzed three-component coupling with gold(I)-mediated 6-endo cyclization streamlines the rapid and modular assembly substructure bis-tetrahydroisoquinoline (THIQ) alkaloids. design key synthetic intermediate bearing a 2,3-diaminobenzofuran moiety allows both regiocontrolled hydroamination temporary protection nitrile phenolic hydroxy groups. strategy enabled efficient synthesis saframycins isoquinoline THIQ units in just four steps from three components. We also found unexpected involvement fluorescent cascade process.

Language: Английский

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Total Syntheses of (+)‐Villocarine A, (−)‐Apogeissoschizine, and (+)‐Geissoschizine

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(18)

Published: Jan. 21, 2023

Total syntheses of geissoschizine-type monoterpenoid indole alkaloids (MTIAs) are reported. An intramolecular Pictet-Spengler cyclization was developed for the selective construction 3R stereocenter. The first total synthesis (+)-villocarine A then achieved. Furthermore, highly strained (-)-apogeissoschizine also accomplished in an aza-Michael cyclization/E1cB elimination/stereoselective olefin isomerization sequence. Finally, (+)-geissoschizine, a common biosynthetic intermediate MTIAs, obtained from apogeissoschizine through ring-opening along with release ring strain.

Language: Английский

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Streamlined Strategy for Scalable and Enantioselective Total Syntheses of the Eburnane Alkaloids

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(36), P. 20062 - 20072

Published: Aug. 30, 2023

A general, concise, and efficient strategy for the enantioselective synthesis of eburnane alkaloid family natural products is disclosed. Specifically, 13 members product were prepared from commercially available inexpensive starting materials. The brevity modularity route are largely on account a two-phase logic key catalytic enantioconvergent cross-coupling to establish C20 stereogenic center. strategies described here expected facilitate in-depth biological studies provide access new anticancer analogues.

Language: Английский

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Unified Strategy Enables the Collective Syntheses of Structurally Diverse Indole Alkaloids

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7616 - 7627

Published: March 6, 2024

Natural products and their analogues are significant sources of therapeutic lead compounds. However, synthetic strategies for generating large collections these molecules remain a challenge. The most difficult step in synthesis is the design common intermediate that can be easily transformed into natural belonging to different families. This study demonstrates evolution tactics designed assemble functionalized piperidines present indole alkaloids from intermediate. More importantly, we also report previously unknown Ir- Er-catalyzed dehydrogenative spirocyclization reaction enables direct access spirocyclic oxindole alkaloids. As practical application, asymmetric total syntheses 29 families were accomplished by following uniform route. proposed methodology extends capability iridium-catalyzed coupling realm indole–alkaloid provides new opportunities efficient preparation product-like molecules.

Language: Английский

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Green Light Promoted Iridium(III)/Copper(I)‐Catalyzed Addition of Alkynes to Aziridinoquinoxalines Through the Intermediacy of Azomethine Ylides

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(12)

Published: Jan. 25, 2024

This manuscript describes the development of alkyne addition to aziridine moiety aziridinoquinoxalines using dual Ir(III)/Cu(I) catalytic system under green light-emitting diode (LED) photolysis (λ

Language: Английский

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Asymmetric Total Synthesis of Alstrostine G Utilizing a Catalytic Asymmetric Desymmetrization Strategy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(34)

Published: May 31, 2024

A highly effective enantioselective monobenzoylation of 1,3-diols has been developed for the synthesis 1,1-disubstituted tetrahydro-β-carbolines. The chemistry successfully applied to asymmetric total (+)-alstrostine G, which also features a cascade Heck/hemiamination reaction enabling facile construction pivotal pentacyclic core.

Language: Английский

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Enantioselective intramolecular Pictet–Spengler type annulation of indole-linked 3-methyleneisoindolin-1-ones

New Journal of Chemistry, Journal Year: 2022, Volume and Issue: 46(20), P. 9582 - 9586

Published: Jan. 1, 2022

Asymmetric intramolecular Pictet–Spengler type annulation of indole-linked 3-methyleneisoindolin-1-ones provided isoindolinone fused tetrahydro β-carbolines with moderate to good enantioselectivities.

Language: Английский

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Iridium‐Catalyzed Reductive (3+2) Annulation of Lactams Enabling the Rapid Total Synthesis of (±)‐Eburnamonine

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(6)

Published: Dec. 13, 2023

A reductive (3+2) annulation of lactams through iridium-catalyzed hydrosilylation and photoredox coupling with α-bromoacetic acid was developed. The the lactam carbonyl group subsequent elimination provide a transient cyclic enamine, which undergoes in one-pot process. developed conditions show high functional-group tolerance N,O-acetals containing quaternary carbon center. resulting undergo variety acid-mediated nucleophilic addition reactions via iminium ions to give substituted amines. sequence including successfully applied four-step total synthesis (±)-eburnamonine.

Language: Английский

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