Ring Expansion Strategies for the Synthesis of Medium Sized Ring and Macrocyclic Sulfonamides DOI Creative Commons
Zhongzhen Yang,

Illya Zalessky,

Ryan G. Epton

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 30, 2023

Two new ring expansion strategies are reported for the synthesis of medium sized and macrocyclic sulfonamides. Both methods can be performed without using classical protecting groups, with key step initiated by nitro reduction amine conjugate addition respectively. Each method used to make diversely functionalised cyclic sulfonamides in good excellent yields, a range sizes. The size dependency synthetic reactions is agreement outcomes modelled Density Functional Theory calculations.

Language: Английский

Construction of Medium-Sized Rings by Gold Catalysis DOI
Ronald L. Reyes, Tomohiro Iwai, Masaya Sawamura

et al.

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(14), P. 8926 - 8947

Published: Oct. 6, 2020

Compounds having cyclic molecular frameworks are highly regarded for their abundance and diverse utilities. In particular, medium-sized carbocycles heterocycles exist in a broad spectrum of natural products, bioactive therapeutics, medicinally significant synthetic molecules. Metal-mediated methods have been developed the preparation compounds containing ring (MSR) through cyclization different classes substrates acyclic precursors. This review focuses on methodologies construction MSRs via gold catalysis. Given challenges enabling assembly sizes, we present here accounts Au-mediated giving notable 7-membered (8–11-membered ring) structures. Emphasis pathway mode selection precursors ranging from structurally biased were outlined. Reactivity patterns choice efficient Au catalysts controlling reaction performance selectivity addition to mechanistic attributes examined.

Language: Английский

Citations

183
Phosphoranyl Radical Fragmentation Reactions Driven by Photoredox Catalysis DOI Creative Commons
James A. Rossi‐Ashton,

Aimee K. Clarke,

William P. Unsworth

et al.

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(13), P. 7250 - 7261

Published: June 5, 2020

Photocatalytic generation of phosphoranyl radicals is fast emerging as an essential method for the diverse and valuable radicals, typically via deoxygenation or desulfurization processes. This Perspective a comprehensive evaluation all studies using tunable mediators in photoredox catalysis, highlighting how two distinct methods radical formation (radical addition nucleophilic addition) can be used to generate versatile intermediates with reactivity profiles.

Language: Английский

Citations

158
FDA‐approved drugs featuring macrocycles or medium‐sized rings DOI Creative Commons

Youlong Du,

Anas Semghouli,

Qian Wang

et al.

Archiv der Pharmazie, Journal Year: 2025, Volume and Issue: 358(1)

Published: Jan. 1, 2025

Abstract Macrocycles or medium‐sized rings offer diverse functionality and stereochemical complexity in a well‐organized ring structure, allowing them to fulfill various biochemical functions, resulting high affinity selectivity for protein targets, while preserving sufficient bioavailability reach intracellular compartments. These features have made macrocycles attractive candidates organic synthesis drug discovery. Since the 20th century, more than three‐score macrocyclic drugs, including radiopharmaceuticals, been approved by US Food Drug Administration (FDA) treating bacterial viral infections, cancer, obesity, immunosuppression, inflammatory, neurological disorders, managing cardiovascular diseases, diabetes, more. This review presents 17 FDA‐approved drugs during past 5 years, highlighting their importance critical role modern therapeutics, innovative synthetic approaches construction of these macrocycles.

Language: Английский

Citations

2
Small rings in the bigger picture: ring expansion of three- and four-membered rings to access larger all-carbon cyclic systems DOI
Bohdan Biletskyi,

P Colonna,

Kévin Masson

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(13), P. 7513 - 7538

Published: Jan. 1, 2021

Ring-expansion of strained small-size rings to forge larger all-carbon ones, allows a rapid build-up molecular complexity.

Language: Английский

Citations

84
Construction of bridged polycycles through dearomatization strategies DOI
Ziying Zhang,

Huabin Han,

Lele Wang

et al.

Organic & Biomolecular Chemistry, Journal Year: 2021, Volume and Issue: 19(18), P. 3960 - 3982

Published: Jan. 1, 2021

Bridged polycycles are privileged molecular skeletons with wide occurrence in bioactive natural products and pharmaceuticals. Therefore, they have been the pursing target molecules of numerous chemists. The rapid convenient generation sp3-rich complex three-dimensional from simple easily available aromatics has made dearomatization a highly valuable synthetic tool for construction rigid challenging bridged rings. This review summarizes the-state-of-the-art advances strategies application ring formation, discusses their advantages limitations in-depth mechanism, highlights value total synthesis products. We wish this will provide an important reference medicinal chemists inspire further development intriguing research area.

Language: Английский

Citations

57
Atroposelective Construction of Nine‐Membered Carbonate‐Bridged Biaryls DOI
Shiqi Jia,

Yuhong Tian,

Xin Li

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 27, 2022

Abstract We herein demonstrated an efficient method for the atroposelective construction of nine‐membered carbonate‐bridged biaryls through vinylidene ortho ‐quinone methide (VQM) intermediates. Diverse products with desirable pharmacological features were synthesized in satisfying yields and good to excellent enantioselectivities. In subsequent bioassays, several agents showed considerable antiproliferative activity via mitochondrial‐related apoptosis mechanism. Further transformations produced more structural diversity may inspire new ideas developing functional molecules.

Language: Английский

Citations

52
Temperature-Controlled Divergent Asymmetric Synthesis of Indole-Based Medium-Sized Heterocycles through Palladium Catalysis DOI
Qing‐Zhu Li,

Yi-Long Guan,

Qianwei Huang

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(2), P. 1164 - 1172

Published: Jan. 4, 2023

The divergent construction of chiral medium-sized rings is an essential but challenging task in organic synthesis. Herein, we report a temperature-controlled catalytic system for the divergent, enantioselective synthesis different types starting from same substrate set. Enabled by planar bisphosphine ligand, palladium-catalyzed (5 + 4) and formal 2) annulations cyclic aza-dienes vinylethylene carbonates proceeded smoothly to afford broad spectrum indole-based heterocycles excellent yields with outstanding enantioselectivities. Those products could be further diversified through various functional group transformations. Moreover, mechanistic studies, including control experiments DFT calculations, shed light on understanding observed regio- enantioselectivities n) cyclization.

Language: Английский

Citations

33
A Modular Strategy for the Synthesis of Macrocycles and Medium-Sized Rings via Cyclization/Ring Expansion Cascade Reactions DOI Creative Commons

Illya Zalessky,

Jack M. Wootton, Jerry K. F. Tam

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5702 - 5711

Published: Feb. 19, 2024

Macrocycles and medium-sized rings are important in many scientific fields technologies but hard to make using current methods, especially on a large scale. Outlined herein is strategy by which functionalized macrocycles can be prepared cyclization/ring expansion (CRE) cascade reactions, without resorting high dilution conditions. CRE reactions designed operate exclusively via kinetically favorable 5–7-membered ring cyclization steps; this means that the problems typically associated with classical end-to-end macrocyclization avoided. A modular synthetic approach has been developed facilitate simple assembly of requisite linear precursors, then converted into an extremely broad range one nine protocols.

Language: Английский

Citations

10
Ruthenium-Catalyzed Carbonylation of α-Aminoaryl-Tethered Alkylidenecyclopropanes: Synthesis of Eight-Membered Benzolactams DOI

Miao-Miao Ji,

Peng-Rui Liu,

Jun-Dong Yan

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(1), P. 231 - 235

Published: Jan. 2, 2024

The synthesis of medium-sized lactams is a great challenge because the unfavorable transannular interactions and entropic barriers in transition state. We have developed ruthenium-catalyzed carbonylation α-aminoaryl-tethered alkylidenecyclopropanes (ACPs) that allows for efficient preparation valuable eight-membered benzolactams under ligand-free conditions. amino group served dual role both directing nucleophile to facilitate metallacycle formation carbonylation.

Language: Английский

Citations

9
Ring Expansion toward Disila‐carbocycles via Highly Selective C−Si/C−Si Bond Cross‐Exchange DOI
Min Liu,

Nuo Yan,

Haowen Tian

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)

Published: Feb. 23, 2024

Herein, we successfully inhibited the preferential homodimerization and C-Si/Si-H bond cross-exchange of benzosilacyclobutenes monohydro-silacyclobutanes achieved first highly selective C-Si/C-Si reaction by deliberately tuning Ni-catalytic system, which constitutes a powerful atom-economical ring expansion method for preparing medium-sized cyclic compounds bearing two silicon atoms at junction, are otherwise inaccessible. The DFT calculation explicitly elucidated pivotal role Si-H silacyclobutanes high strain substrates in realizing C-Si bonds cleavage reformation catalytic cycle.

Language: Английский

Citations

9