Biosynthesis of pyrroloindoline-containing natural products

Natural Product Reports, Journal Year: 2022, Volume and Issue: 39(9), P. 1721 - 1765

Published: Jan. 1, 2022

Covering: up to 2022Pyrroloindoline is a privileged tricyclic indoline motif widely present in many biologically active and medicinally valuable natural products. Thus, understanding the biosynthesis of this molecule critical for developing convenient synthetic routes, which highly challenging its chemical synthesis due presence rich chiral centers molecule, especially fully substituted carbon center at C3-position rigid structure. In recent years, progress has been made elucidating biosynthetic pathways enzymatic mechanisms pyrroloindoline-containing products (PiNPs). This article reviews main advances past few decades based on different substitutions C3 position PiNPs, various key involved types PiNPs.

Language: Английский

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Highly efficient construction of 2,3-disubstituted indoline derivatives by [4 + 1] annulation of sulfur ylides and o-sulfonamido aldimines

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(6), P. 1521 - 1526

Published: Jan. 1, 2023

A highly efficient [4 + 1] annulation of sulfur ylide salts and o -sulfonamido aldimines for construction valuable 2,3-disubstituted indolines is reported. It worth noting that indoles could also be synthesized by this cascade reaction.

Language: Английский

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Accessing ladder-shape azetidine-fused indoline pentacycles through intermolecular regiodivergent aza-Paternò–Büchi reactions

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

Published: Feb. 16, 2024

Abstract Small molecules with conformationally rigid, three-dimensional geometry are highly desirable in drug development, toward which a direct, simple-to-complexity synthetic logic is still of considerable challenges. Here, we report intermolecular aza-[2 + 2] photocycloaddition (the aza-Paternò–Büchi reaction) indole that facilely assembles planar building blocks into ladder-shape azetidine-fused indoline pentacycles contiguous quaternary carbons, divergent head-to-head/head-to-tail regioselectivity, and absolute exo stereoselectivity. These products exhibit marked three-dimensionality, many possess 3D score values distributed the highest 0.5% region reference to structures from DrugBank database. Mechanistic studies elucidated origin observed regio- stereoselectivities, arise distortion-controlled C-N coupling scenarios. This study expands repertoire energy transfer catalysis for accessing structurally intriguing architectures high molecular complexity underexplored topological chemical space.

Language: Английский

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Dearomative (3 + 2) Cycloadditions of 3-Nitroheteroarenes with Allenyl Sulfones Mediated by Ion Pair Organocatalysis

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

Published: Feb. 8, 2025

We report the first example of dearomative (3 + 2) cycloadditions 3-nitro(aza)-indole, -benzofuran, and -benzothiophene derivatives in presence allenyl sulfones, using sulfinate ammonium ion pairs as organocatalytic promoters. The methodology provides a new, facile, efficient protocol for synthesis functionalized 2,3-fused cyclopentannulated indolines dihydrobenzofurans.

Language: Английский

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The Rational Design and Atroposelective Synthesis of Axially Chiral C2‐Arylpyrrole‐Derived Amino Alcohols

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(36)

Published: June 21, 2022

Abstract Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially amino alcohols are far less developed. Herein, we rationally designed a versatile C 1 ‐symmetric alcohol scaffold 1‐(1‐amino‐pyrrol‐2‐yl)naphthalen‐2‐ol (NPNOL) on the basis of C2‐arylpyrrole framework. For its enantioselective synthesis, phosphoric acid‐catalyzed Attanasi reaction between 1,3‐dicarbonyl compounds and azoalkenes had been established. using this practical method, wide range NPNOLs were readily prepared high yields excellent atroposelectivities (38 examples, up to 89 % yield 99 ee ). DFT calculations performed reveal mechanism origins enantioselectivity. The easy transformations NPNOL‐derived products into organocatalysts/ligands their preliminary applications catalytic reactions demonstrated promising utility NPNOL.

Language: Английский

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De Novo Construction of Chiral Aminoindolines by Cu-Catalyzed Asymmetric Cyclization and Subsequent Discovery of an Unexpected Sulfonyl Migration

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(43), P. 19932 - 19941

Published: Oct. 21, 2022

Searching for efficient strategies to access structurally novel aminoindolines is of great significance drug discovery. However, catalytic asymmetric de novo construction aminoindoline scaffolds with functionality primed diversification still remains elusive. Here, we report a Cu-catalyzed cyclization ethynyl benzoxazinones amines, producing chiral 3-aminoindolines in good yield and high enantioselectivity (up 97% 98:2 er). Moreover, radical-mediated sulfonyl migration these products was unexpectedly found, further affording new bearing alkenyl groups retained enantiopurity 84% Bioactivity evaluations indicate that show notable antitumor activities chirality proven have significant impact on their activity.

Language: Английский

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Recent Advances on Direct Functionalization of Indoles in Aqueous Media

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(3)

Published: Feb. 1, 2023

Abstract Indoles and their derivatives have dominated a significant proportion of nitrogen‐containing heterocyclic compounds play an essential role in synthetic medicinal chemistry, pesticides, advanced materials. Compared with conventional strategies, direct functionalization indoles provides straightforward access to construct diverse indole scaffolds. As we enter era emphasizing green sustainable utilizing environment‐friendly solvents represented by water demonstrates great potential synthesizing valuable derivatives. This review aims depict the critical aspects aqueous‐mediated over past decade discusses future challenges prospects this fast‐growing field. For convenience readers, is classified into three parts according bonding modes (C−C, C−N, C−S bonds), which focus on diversity derivatives, prominent chemical process, types catalyst systems mechanisms. We hope can promote development discovery novel practical organic methods aqueous phase.

Language: Английский

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Dearomative [4 + 2] cycloaddition of 3‐nitroindoles with ortho‐amino Morita−Baylis−Hillman carbonates to forge indole‐fused quinolines

Journal of Heterocyclic Chemistry, Journal Year: 2024, Volume and Issue: 61(3), P. 528 - 537

Published: Jan. 16, 2024

Abstract A dearomative [4 + 2] cycloaddition of 3‐nitroindoles ortho ‐amino Morita−Baylis−Hillman carbonates was established under mild conditions. This method provides an efficient and practical approach for delivering tetrahydro‐5 H ‐indolo[2,3‐ b ]quinolines containing three contiguous stereocenters, two tertiary one quaternary, in high yield (up to 95%) with excellent diastereoselectivity (all cases >25:1 dr ). The potential synthetic applications this strategy were also highlighted by the scale‐up experiment further transformation. Moreover, structure relative configuration cycloadduct unequivocally confirmed single‐crystal X‐ray diffraction.

Language: Английский

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Benzylic C(sp3)–H Functionalization via Copper-Catalyzed [3+3] Radical Cycloaddition

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(8), P. 5605 - 5611

Published: March 29, 2024

The development of benzylic C(sp3)–H functionalization methods for the assembly derivatives has been extensively explored in recent years. However, engagement carbon and its adjacent C=C bond as a C3 synthon cycloaddition reaction via direct C–H activation is rare. Herein, we report copper-catalyzed [3+3] radical through to construct six-membered cyclohexane-type rings. In this reaction, 2-benzylic an indole selectively activated serves that reacts highly chemoselective intermolecular self-[3+3] cross-[3+3] pathways. Multiple symmetric nonsymmetric polycyclic hexahydrocarbazole scaffolds with hexacyclic 6/5/5/6/5/5/6 pentacyclic 6/5/5/6/5/6 ring systems are synthesized high efficiency chemoselectivity using strategy. Inspired by unique addition pathway cycloaddition, controllable construction C3a-alkylated pyrroloindolines was also developed.

Language: Английский

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Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3310 - 3315

Published: April 8, 2024

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable triggering dearomatization 3-nitroindoles for diastereo- enantioselective [3+2] cycloaddition, leading formation series highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up 99% yield, 88:12 dr, 96% ee).

Language: Английский

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