Mechanistic Study on the Gold-Catalyzed C−S Bond Formation of α-Thioallenes To Form 2,5-Dihydrothiophenes

2010 ◽  
Vol 75 (24) ◽  
pp. 8516-8521 ◽  
Author(s):  
Kaori Ando
Keyword(s):  
Bond Formation ◽  
Mechanistic Study

Dirhodium(II)-Catalyzed Diamination Reaction via a Free Radical Pathway

2021 ◽  
Author(s):  
Zhiying Fan ◽  
Zhifan Wang ◽  
Ruoyi Shi ◽  
Yuanhua Wang
Keyword(s):  
Free Radical ◽  
Bond Formation ◽  
Mechanistic Study ◽  
Radical Mechanism ◽  
Free Radical Mechanism

Unlike C-N bond formation with classical dirhodium(II)-nitrenoids as the key intermediate, dirhodium(II)-catalyzed 1,2-and 1,3-diamination reactions are realized by a free radical mechanism. A mechanistic study revealed that the reactions undergo...

scholarly journals Mechanism of Covalent Binding of Ibrutinib to Bruton’s Tyrosine Kinase revealed by QM/MM Calculations

2020 ◽  
Author(s):  
Angus Voice ◽  
Gary Tresadern ◽  
Rebecca Twidale ◽  
Herman Van Vlijmen ◽  
Adrian Mulholland
Keyword(s):  
Tyrosine Kinase ◽  
Covalent Binding ◽  
Bond Formation ◽  
Covalent Bond ◽  
Covalent Modification ◽  
Mechanistic Study ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Covalent Inhibitors ◽  
Covalent Bond Formation

<p>Ibrutinib is the first covalent inhibitor of Bruton’s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers. Understanding the mechanism of covalent inhibition is crucial for the design of safer and more selective covalent inhibitors that target BTK. There are questions surrounding the precise mechanism of covalent bond formation in BTK as there is no appropriate active site residue that can act as a base to deprotonate the cysteine thiol prior to covalent bond formation. To address this, we have investigated several mechanistic pathways of covalent modification of C481 in BTK by ibrutinib using QM/MM reaction simulations. The lowest energy pathway we identified involves a direct proton transfer from C481 to the acrylamide warhead in ibrutinib, followed by covalent bond formation to form an enol intermediate. There is a subsequent rate-limiting keto-enol tautomerisation step (DG<sup>‡</sup>=10.5 kcal mol<sup>-1</sup>) to reach the inactivated BTK/ibrutinib complex. Our results represent the first mechanistic study of BTK inactivation by ibrutinib to consider multiple mechanistic pathways. These findings should aid in the design of covalent drugs that target BTK and related proteins. </p>

scholarly journals Mechanism of Covalent Binding of Ibrutinib to Bruton’s Tyrosine Kinase revealed by QM/MM Calculations

2020 ◽  
Author(s):  
Angus Voice ◽  
Gary Tresadern ◽  
Rebecca Twidale ◽  
Herman Van Vlijmen ◽  
Adrian Mulholland
Keyword(s):  
Tyrosine Kinase ◽  
Covalent Binding ◽  
Bond Formation ◽  
Covalent Bond ◽  
Covalent Modification ◽  
Mechanistic Study ◽  
Bruton’S Tyrosine Kinase ◽  
Bruton's Tyrosine Kinase ◽  
Covalent Inhibitors ◽  
Covalent Bond Formation

<p>Ibrutinib is the first covalent inhibitor of Bruton’s tyrosine kinase (BTK) to be used in the treatment of B-cell cancers. Understanding the mechanism of covalent inhibition is crucial for the design of safer and more selective covalent inhibitors that target BTK. There are questions surrounding the precise mechanism of covalent bond formation in BTK as there is no appropriate active site residue that can act as a base to deprotonate the cysteine thiol prior to covalent bond formation. To address this, we have investigated several mechanistic pathways of covalent modification of C481 in BTK by ibrutinib using QM/MM reaction simulations. The lowest energy pathway we identified involves a direct proton transfer from C481 to the acrylamide warhead in ibrutinib, followed by covalent bond formation to form an enol intermediate. There is a subsequent rate-limiting keto-enol tautomerisation step (DG<sup>‡</sup>=10.5 kcal mol<sup>-1</sup>) to reach the inactivated BTK/ibrutinib complex. Our results represent the first mechanistic study of BTK inactivation by ibrutinib to consider multiple mechanistic pathways. These findings should aid in the design of covalent drugs that target BTK and related proteins. </p>

Mechanistic Study of Ni and Cu Dual Catalyst for Asymmetric C–C Bond Formation; Asymmetric Coupling of 1,3-Dienes with C-nucleophiles to Construct Vicinal Stereocenters

ACS Catalysis ◽  
2021 ◽  
pp. 6643-6655
Author(s):  
Jingzhao Xia ◽  
Takahiro Hirai ◽  
Shoichiro Katayama ◽  
Haruki Nagae ◽  
Wanbin Zhang ◽  
...  
Keyword(s):  
Bond Formation ◽  
Mechanistic Study ◽  
Asymmetric Coupling

Mechanistic Study of a Photocatalyzed CS Bond Formation Involving Alkyl/Aryl Thiosulfate

2015 ◽  
Vol 21 (45) ◽  
pp. 16059-16065 ◽  
Author(s):  
Yiming Li ◽  
Weisi Xie ◽  
Xuefeng Jiang
Keyword(s):  
Bond Formation ◽  
Mechanistic Study ◽  
Alkyl Aryl

Diacetoxyiodobenzene assisted C–O bond formation via sequential acylation and deacylation process: synthesis of benzoxazole amides and their mechanistic study by DFT

2016 ◽  
Vol 14 (32) ◽  
pp. 7735-7745 ◽  
Author(s):  
Lokendrajit Nahakpam ◽  
Francis A. S. Chipem ◽  
Brajakishor S. Chingakham ◽  
Warjeet S. Laitonjam
Keyword(s):  
Oxidative Dehydrogenation ◽  
Efficient Method ◽  
Bond Formation ◽  
Process Synthesis ◽  
Mechanistic Study

An efficient method for the transformation of N-substituted-N′-benzoylthioureas to substituted N-benzoxazol-2-yl-amides due to oxidative dehydrogenation by diacetoxyiodobenzene.

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