Enantioselective Total Syntheses of Vallesamidine and Schizozygane Alkaloids

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

A general streamlined strategy for the enantioselective total syntheses of schizozygane family natural products and related alkaloid vallesamidine is described. Specifically, a catalytic enantioconvergent cross-coupling sets quaternary stereogenic center in pluripotent intermediate adorned with an olefin three orthogonal carboxylate groups, upon which modularity synthesis relies. late-stage oxidative lactamization alkyne instrumental first-generation alkaloids. In second-generation approach, novel application van Leusen reaction generation lactams pivotal to accessing alkaloids from common intermediate. The strategies outlined here are expected enable detailed biological investigations as well facilitate access provide solutions modification bioactive

Language: Английский

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Homo-Mannich Reaction of Cyclopropanols: A Versatile Tool for Natural Product Synthesis

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

ConspectusThe Mannich reaction, involving the nucleophilic addition of an enol(ate) intermediate to imine or iminium ion, is one most widely used synthetic methods for synthesis β-amino carbonyl compounds. Nevertheless, homo-Mannich which utilizes a homoenolate as partner and provides straightforward access valuable γ-amino compounds, remains underexplored. This can be largely attributed difficulties in generation manipulation species, despite various equivalents that have been developed. Among developed, cyclopropanol stands out due its intriguing reactivities endowed by highly strained cyclopropane. Upon activation metal, cyclopropyl alcohol prone undergo endocyclic C(sp3)–C(sp3) bond cleavage give β-keto radical intermediate, sets stage diverse range transformations. account outlines our recent progress development reaction applications natural product total synthesis. new methodology classified into two subtypes: 1) with imines ions 2) homo-Mannich-type heteroarenes. Through different ways generate ions, tandem sequential reactions C–H oxidation/homo-Mannich, Bischler–Napieralski/homo-Mannich, asymmetric allylation/homo-Mannich leading rapid assembly core scaffolds sarpagine, koumine, ibophyllidine, Aspidosperma, Melodinus, Kopsia alkaloids. Besides ring-opening indole pyrrole rings deliver schizozygane indolizidine Based on these advancements, we accomplished 29 alkaloids belonging 8 families. In this Account, present complete picture works concerning design, method development, It anticipated methodologies will find broad realm

Language: Английский

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Total Synthesis of Melonine

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Total synthesis of melonine was accomplished. A cycloheptene unit and a quinoline were connected via Stille coupling. The core cleaved with thiophosgene to liberate the arylamine moiety. Oxidative intramolecular aziridination, followed by nucleophilic attack moiety aziridine ring, constructed characteristic cyclic system trans-1,2-diamine structure. Stereoselective hydrogenation formation piperidine ring led melonine.

Language: Английский

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Divergent Construction of Spirocyclopentene-3,2′-indolines with Vicinal Stereocenters via Palladium-Catalyzed Aza-Wacker Cyclization

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Herein, we report an aerobic palladium-catalyzed aza-Wacker cyclization to produce spirocyclopentene-3,2'-indolines with vicinal stereocenters. Using 1,2-bis(diphenylphosphino)benzene (dppbz) and pyridine as ligands, achieved a ligand-modulated diastereodivergent synthesis, producing cis- trans-spirocyclopentene-3,2'-indolines exceptional yields diastereoselectivities. Density functional theory (DFT) calculations revealed that selective proceeds through distinct trans- cis-aminopalladation mechanisms.

Language: Английский

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Translating community-wide spectral library into actionable chemical knowledge: a proof of concept with monoterpene indole alkaloids

Journal of Cheminformatics, Journal Year: 2025, Volume and Issue: 17(1)

Published: April 28, 2025

Language: Английский

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Enantioselective Total Synthesis of (−)-Vallesamidine Enabled by Asymmetric Hydrogenation and Aza-Wacker Cyclization to Construct the Core Spirocyclopentane-1,2′-indoline Structure

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 22, 2025

An enantioselective total synthesis of (-)-vallesamidine is described, integrating asymmetric hydrogenation with aza-Wacker cyclization to form the chiral spirocyclopentane-1,2'-indoline. Intramolecular Stetter reaction and alkylation are employed construct a tetracyclic framework featuring quaternary carbon center. Schmidt rearrangement intramolecular aldol condensation facilitate formation D E rings. This achieves in 14 steps an overall yield 4.2% from exocyclic enone ester.

Language: Английский

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Enantioselective Construction of Tetrahydroindole Skeletons by Rh‐Catalyzed [2+2+2] Cycloaddition of Homopropargyl Enamides with Alkynes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(38)

Published: June 26, 2024

We have developed the Rh-catalyzed enantioselective [2+2+2] cycloaddition of homopropargyl enamides (tosylamide-tethered 1,6-enynes) with alkynes to construct tetrahydroindole skeletons found in natural alkaloids and pharmaceuticals. This proceeds at room temperature high yields regio- enantioselectivity a broad substrate scope. The preparative scale reaction followed by substituent conversion on nitrogen atom diastereoselective [4+2] singlet O

Language: Английский

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Enantioselective Construction of Tetrahydroindole Skeletons by Rh‐Catalyzed [2+2+2] Cycloaddition of Homopropargyl Enamides with Alkynes

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(38)

Published: June 26, 2024

Abstract We have developed the Rh‐catalyzed enantioselective [2+2+2] cycloaddition of homopropargyl enamides (tosylamide‐tethered 1,6‐enynes) with alkynes to construct tetrahydroindole skeletons found in natural alkaloids and pharmaceuticals. This proceeds at room temperature high yields regio‐ enantioselectivity a broad substrate scope. The preparative scale reaction followed by substituent conversion on nitrogen atom diastereoselective [4+2] singlet O 2 affords hexahydroindole‐diols bearing three stereogenic centers variable substituents nitrogen. Mechanistic studies revealed that enynes change ratio intramolecular intermolecular rhodacycle formation when using terminal alkynes, varying ee values cycloadducts.

Language: Английский

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Organocatalytic Asymmetric Construction of 2,6‐Diazabicyclo[2.2.2]octanes by Harnessing the Potential of an 3‐Oxindolium Ion Intermediate

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6‐diazabicyclo[2.2.2]octane (2,6‐DABCO) has remained a highly desirable target in synthetic chemistry. However, the asymmetric access this unit is still insufficient hampered by need for meticulously created functionalities intricate double aza‐cyclizations. Herein, we have developed novel enantio‐ diastereoselective protocol polycyclic chiral 2,6‐DABCOs under metal‐free conditions. This domino process involves amine‐catalyzed [4+2] annulation between glutaraldehyde 2‐arylindol‐3‐ones, followed an acid‐mediated Pictet–Spengler reaction/intramolecular aza‐cyclization cascade sequence with tryptamine trapping situ generated 3‐oxindolium ion intermediate first time. Overall, fused medicinally relevant scaffolds were isolated good yield excellent stereoselectivity constructing five new bonds four stereocenters one‐pot operation.

Language: Английский

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Organocatalytic Asymmetric Construction of 2,6‐Diazabicyclo[2.2.2]octanes by Harnessing the Potential of an 3‐Oxindolium Ion Intermediate

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6-diazabicyclo[2.2.2]octane (2,6-DABCO) has remained a highly desirable target in synthetic chemistry. However, the asymmetric access this unit is still insufficient hampered by need for meticulously created functionalities intricate double aza-cyclizations. Herein, we have developed novel enantio- diastereoselective protocol polycyclic chiral 2,6-DABCOs under metal-free conditions. This domino process involves amine-catalyzed [4+2] annulation between glutaraldehyde 2-arylindol-3-ones, followed an acid-mediated Pictet-Spengler reaction/intramolecular aza-cyclization cascade sequence with tryptamine trapping situ generated 3-oxindolium ion intermediate first time. Overall, fused medicinally relevant scaffolds were isolated good yield excellent stereoselectivity constructing five new bonds four stereocenters one-pot operation.

Language: Английский

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