CYP3A Mediates an Unusual C(sp2)−C(sp3) Bond Cleavage via Ipso‐Addition of Oxygen in Drug Metabolism DOI
Xuan Qin, Yong Wang, Qiuji Ye

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(23)

Published: April 4, 2024

Abstract Mammalian cytochrome P450 drug‐metabolizing enzymes rarely cleave carbon–carbon (C−C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual non‐polar, unstrained C(sp 2 )−C(sp 3 ) in FDA‐approved tyrosine kinase inhibitor pexidartinib that mediated by CYP3A4/5, major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out Baeyer–Villiger oxidation mechanism is commonly invoked to address P450‐mediated C−C bond cleavages. Our studies 18 O H enriched systems reveal distinct cleavage: one cleaved CYP3A‐mediated ipso ‐addition oxygen site N ‐protected pyridin‐2‐amines, other occurs pseudo‐retro‐aldol reaction after hydroxylation site. This first report cleavage metabolism via mechanism. also implicated regioselective several analogs. The regiospecificity CYP3A‐catalyzed under environmentally friendly conditions may be attractive inspire biomimetic or P450‐engineering methods challenging task

Language: Английский

Transition‐Metal‐Free Deconstructive Lactamization of Piperidines DOI
Julio Romero‐Ibañez, Silvano Cruz‐Gregorio, Jacinto Sandoval‐Lira

et al.

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(26), P. 8867 - 8871

Published: April 18, 2019

Abstract One of the major challenges in organic synthesis is activation or deconstructive functionalization unreactive C(sp 3 )–C(sp ) bonds, which requires using transition precious metal catalysts. We present here an alternative: lactamization piperidines without To this end, we use 3‐alkoxyamino‐2‐piperidones, were prepared from through a dual )–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that unprecedented occurs tandem manner involving oxidative deamination 3‐alkoxyamino‐2‐piperidones to 3‐keto‐2‐piperidones, followed by regioselective Baeyer–Villiger oxidation give N ‐carboxyanhydride intermediates, finally undergo spontaneous concerted decarboxylative intramolecular translactamization.

Language: Английский

Citations

27
Visible light-induced borylation and arylation of small organic molecules using carbon dots DOI

Tiantong He,

Heping Wei,

Yuanbo Zhou

et al.

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(12), P. 2918 - 2926

Published: Jan. 1, 2023

Efficient synthetic protocols for borylation of haloarenes and arylation heteroarenes using nonmetal-doped CDots as metal-free photocatalysts under visible-light irradiation at room temperature are reported.

Language: Английский

Citations

8
Generation of aryl radicals by redox processes. Recent progress in the arylation methodology DOI
Dmitry I. Bugaenko, Alexey A. Volkov, Alexander V. Karchava

et al.

Russian Chemical Reviews, Journal Year: 2020, Volume and Issue: 90(1), P. 116 - 170

Published: July 18, 2020

Arylation methods based on the generation and use of aryl radicals have been a rapidly growing field research in recent years currently represent powerful strategy for carbon – heteroatom bond formation. The progress this is related to advances radicals. used radical precursors include halides, aryldiazonium diaryliodonium salts, arylcarboxylic acids their derivatives, arylboronic acids, arylhydrazines, organosulfur(II, VI) compounds some other compounds. Aryl are generated under mild conditions by single electron reduction or oxidation induced conventional reagents, visible light electric current. A crucial role development arylation methodology belongs photoredox processes either catalyzed transition metal complexes organic dyes proceeding without catalysts. Unlike metal-catalyzed methods, reactions proceed very often at room temperature high functional group tolerance. Without claiming be exhaustive, review covers most important current decade synthetic applications (het)aryl Examples given mechanistic insights highlighted. bibliography includes 341 references.

Language: Английский

Citations

21
Acid-Promoted Intramolecular Decarbonylative Coupling Reactions of Unstrained Ketones: A Modular Approach to Synthesis of Acridines and Diaryl Ketones DOI
Ganesh Kumar Dhandabani,

Chia-Ling Shih,

Jeh‐Jeng Wang

et al.

Organic Letters, Journal Year: 2020, Volume and Issue: 22(5), P. 1955 - 1960

Published: Feb. 19, 2020

Herein, we reported Lewis acid- or Brønsted acid-promoted intramolecular C(sp2)-C(sp2) bond cleavage and a novel bond-forming cascade reaction to synthesize the acridine motif. The metal-free oxidation of alkyne motif generated in situ ketone group extracted via decarbonylation reaction. mechanistic studies revealed that electrophilic N-iodo species triggered key reactions consecutive dearomatization/aromatization reactions. In addition, exploited this C–C activation system with internal alkynes bis(heteroaryl) ketones.

Language: Английский

Citations

19
Recent progress in C(aryl)–C(alkyl) bond cleavage of alkylarenes DOI Open Access

Pengfei Dai,

Hua Wang,

Xian‐Chao Cui

et al.

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 7(6), P. 896 - 904

Published: Jan. 1, 2020

Cleavage of the C(aryl)–C(alkyl) σ-bond is important both in academy and industry as it holds potential to provide straightforward access a variety targets from readily available chemical feedstocks such like alkylarenes.

Language: Английский

Citations

19
tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides DOI

Pengfei Dai,

Yiping Wang, Jian‐Ping Qu

et al.

Organic Letters, Journal Year: 2021, Volume and Issue: 23(24), P. 9360 - 9364

Published: Nov. 24, 2021

A synthetically practical transition metal/catalyst/halogen-free dehydrogenative coupling of aldehydes with N-hydroxyimides promoted solely by tert-butyl nitrite under mild conditions was developed. tert-Butyl generates two radicals (tBuO and NO) thus works as a twofold hydrogen abstractor. diverse array N-hydroxyimide esters were prepared from either aliphatic or aromatic aldehydes. Benzoyl-substituted such 2-oxo-2-phenylacetaldehyde are also suitable.

Language: Английский

Citations

16
Solvent-controlled chemoselective N-dealkylation-N-nitrosation or C-nitration of N-alkyl anilines with tert-butyl nitrite DOI
Xuanhua Guo,

Chengdong Lv,

Qaiser Mahmood

et al.

Organic Chemistry Frontiers, Journal Year: 2019, Volume and Issue: 6(19), P. 3401 - 3407

Published: Jan. 1, 2019

A metal-free, acid-free and chemoselective N-dealkylation-N-nitrosation or C-nitration of N-alkyl anilines has been developed.

Language: Английский

Citations

18
Synthesis of 1,4-Biphenyl-triazole Derivatives as Possible 17β-HSD1 Inhibitors: An in Silico Study DOI Creative Commons
Hiram Hernández‐López, Socorro Leyva‐Ramos, César F. A. Gómez‐Durán

et al.

ACS Omega, Journal Year: 2020, Volume and Issue: 5(23), P. 14061 - 14068

Published: June 1, 2020

Triazoles occupy an important position in medicinal chemistry because of their various biological activities. The structural features 1,2,3-triazoles enable them to act as a bioisostere different functional groups such amide, ester, carboxylic acid, and heterocycle, being capable forming hydrogen bonds π-π interactions or coordinate metal ions with targets. In this work, the synthesis 1,2,3-triazole derivatives via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is reported. Overexpression 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) often found breast cancer cells. Molecular similarity docking analysis were used evaluate potential inhibitory activity synthesized over 17β-HSD1 for treatment mammary tumors. Our silico shows that compounds 4c, 4d, 4f, 4g, 4j are good molecular scaffold candidates inhibitors.

Language: Английский

Citations

15
Decarboxylative Amidation of Aryl/Heteroarylacetic Acids via Activated Esters through Traceless α-Functionalized Benzylic Radicals DOI
Joydev K. Laha,

Upma Gulati,

Anjali Gupta

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(19), P. 3402 - 3406

Published: May 9, 2023

Unlike conventional amide synthesis, a decarboxylative amidation of aryl/heteroarylacetic acids by reaction with NHS and tert-butyl nitrite has been reported to afford both aliphatic (hetero)aromatic amides in satisfactory yields. Mechanistic studies revealed previously unexplored pathway for the formation an activated ester through generation subsequent reactions traceless α-functionalized benzylic radicals, which upon one-pot amines form amides. A gram-scale synthesis Moclobemide indicates practical applicability.

Language: Английский

Citations

5
Iridium-Mediated Arylation of Quinoline via the Cleavage of Carbon–Carbon and Carbon–Nitrogen Bonds of 1,3-Dimesitylimidazol-2-ylidene DOI

Shun Sakurai,

Mamoru Tobisu

Organometallics, Journal Year: 2019, Volume and Issue: 38(14), P. 2834 - 2838

Published: June 28, 2019

The iridium-mediated direct arylation of quinoline using an NHC ligand is reported. This reaction proceeds via cleavage the carbon–carbon and carbon–nitrogen bonds a carbon–hydrogen bond quinoline.

Language: Английский

Citations

15