Expedient synthesis of 3-phenylbicyclo[1.1.1]pentan-1-amine via metal-free homolytic aromatic alkylation of benzene

2015 ◽  
Vol 51 (15) ◽  
pp. 3139-3142 ◽  
Author(s):  
Navanita T. Thirumoorthi ◽  
Chew Jia Shen ◽  
Vikrant A. Adsool
Keyword(s):  
Lead Optimization ◽  
Metal Free ◽  
Alkylation Of Benzene ◽  
Homolytic Alkylation

The inquisitiveness on the use of the BCP motif as a modern lead optimization tactic entails reliable synthetic access. In that direction, we disclose a new and versatile approach to 3-phenylbicyclo[1.1.1]pentan-1-amine, via metal-free homolytic alkylation of benzene.

scholarly journals Direct Alkylation of Benzene at Lower Temperatures in the Liquid Phase: Catalysis by Montmorillonites as Noble‐Metal‐Free Solid Acids

ChemPlusChem ◽  
2020 ◽  
Vol 85 (3) ◽  
pp. 450-453
Author(s):  
Moe Takabatake ◽  
Masayuki Nambo ◽  
Yuichi Manaka ◽  
Ken Motokura
Keyword(s):  
Liquid Phase ◽  
Noble Metal ◽  
Solid Acids ◽  
Metal Free ◽  
Alkylation Of Benzene

The Shadow Widths of Very Small Particles are Formed Independently of the Metal Cap Build Up on the Particle

1981 ◽  
Vol 39 ◽  
pp. 568-569
Author(s):  
George C. Ruben
Keyword(s):  
Gold Particle ◽  
Film Surface ◽  
Small Particles ◽  
Geometric Process ◽  
Metal Free ◽  
Shadow Area

The formation of shadows behind small particles has been thought to be a geometric process (GP) where the metal cap build up on the particle creates a shadow width the same size as or larger than the particle. This GP cannot explain why gold particle shadow widths are generally larger than the gold particle and may have no appreciable metal cap build up (fig. 1). Ruben and Telford have suggested that particle shadow widths are formed by the width dependent deflection of shadow metal (SM) lateral to and infront of the particle. The trajectory of the deflected SM is determined by the incoming shadow angle (45°). Since there can be up to 1.4 times (at 45°) more SM directly striking the particle than the film surface, a ridge of metal nuclei lateral to and infront of the particle can be formed. This ridge in turn can prevent some SM from directly landing in the metal free shadow area. However, the SM that does land in the shadow area (not blocked by the particle or its ridge) does not stick and apparently surface migrates into the SM film behind the particle.

Recent advancement in the electrocatalytic synthesis of ammonia

Nanoscale ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 8065-8094 ◽  
Author(s):  
Xudong Wen ◽  
Jingqi Guan
Keyword(s):  
Metal Oxide ◽  
Oxide Catalysts ◽  
Single Atom ◽  
Metal Oxide Catalysts ◽  
Metal Free ◽  
Recent Advancement ◽  
Nanocomposite Catalysts

Different kinds of electrocatalysts used in NRR electrocatalysis (including single atom catalysts, metal oxide catalysts, nanocomposite catalysts, and metal free catalysts) are introduced.

Transition-metal-free catalytic hydroboration reduction of amides to amines

2020 ◽  
Vol 7 (21) ◽  
pp. 3515-3520
Author(s):  
Wubing Yao ◽  
Jiali Wang ◽  
Aiguo Zhong ◽  
Shiliang Wang ◽  
Yinlin Shao
Keyword(s):  
Transition Metal ◽  
Selective Catalytic Reduction ◽  
Catalytic Reduction ◽  
Value Added ◽  
Metal Free

The selective catalytic reduction of amides to value-added amine products is a desirable but challenging transformation.

Deaminative carbonylative thioesterification of activated alkylamines with thiophenols under transition-metal-free conditions

2021 ◽  
Author(s):  
Fengqian Zhao ◽  
Xiao-Feng Wu
Keyword(s):  
Free Radical ◽  
Transition Metal ◽  
Metal Free

A transition-metal-free radical carbonylation of activated alkylamines with thiophenols has been successfully developed. Various thioesters were selectively produced with moderate to good yields.

Stereodivergent Alkyne Hydrofluorination Using a Simple Practical Reagent

2020 ◽  
Author(s):  
Rui Guo ◽  
Xiaotian Qi ◽  
Hengye Xiang ◽  
Paul Geaneoates ◽  
Ruihan Wang ◽  
...  
Keyword(s):  
Bond Formation ◽  
Biologically Active ◽  
Dft Studies ◽  
Thermodynamic Control ◽  
Important Goal ◽  
Peptide Bonds ◽  
Metal Free ◽  
Vinyl Cation ◽  
E And Z Isomers ◽  
Vinyl Fluorides

Vinyl fluorides play an important role in drug development as they serve as bioisosteres for peptide bonds and are found in a range of biologically active molecules. The discovery of safe, general and practical procedures to prepare vinyl fluorides remains an important goal and challenge for synthetic chemistry. Here we introduce an inexpensive and easily-handled reagent and report simple, scalable, and metal-free protocols for the regioselective and stereodivergent hydrofluorination of alkynes to access both the E and Z isomers of vinyl fluorides. These conditions were suitable for a diverse collection of alkynes, including several highly-functionalized pharmaceutical derivatives. Mechanistic and DFT studies support C–F bond formation through a vinyl cation intermediate, with the (E)- and (Z)-hydrofluorination products forming under kinetic and thermodynamic control, respectively.<br>

Metal-Free Photoinduced Hydroalkylation Cascade Enabled by an Electron-Donor-Acceptor Complex

2020 ◽  
Author(s):  
José Tiago Menezes Correia ◽  
Gustavo Piva da Silva ◽  
Camila Menezes Kisukuri ◽  
Elias André ◽  
Bruno Pires ◽  
...  
Keyword(s):  
Electron Donor ◽  
Functional Group ◽  
Photoexcited Electron ◽  
One Pot ◽  
Quaternary Centers ◽  
Metal Free ◽  
Acceptor Complex ◽  
Catalyst Free ◽  
Donor Acceptor ◽  
Radical Cascade

A metal- and catalyst-free photoinduced radical cascade hydroalkylation of 1,7-enynes has been disclosed. The process is triggered by a SET event involving a photoexcited electron-donor-aceptor complex between NHPI ester and Hantzsch ester, which decomposes to afford a tertiary radical that is readily trapped by the enyne. <a>The method provides an operationally simple, robust and step-economical approach to the construction of diversely functionalized dihydroquinolinones bearing quaternary-centers. A sequential one-pot hydroalkylation-isomerization approach is also allowed giving access to a family of quinolinones. A wide substrate scope and high functional group tolerance was observed in both approaches</a>.

AutoLinker: Automatic Fragment Linking with Deep Conditional Transformer Neural Networks

2020 ◽  
Author(s):  
Yuyao Yang ◽  
Shuangjia Zheng ◽  
Shimin Su ◽  
Jun Xu ◽  
Hongming Chen
Keyword(s):  
Neural Networks ◽  
Drug Discovery ◽  
Drug Design ◽  
State Of The Art ◽  
The State ◽  
Generative Model ◽  
Lead Optimization ◽  
Scaffold Hopping ◽  
Reference Models ◽  
Lead Generation

Fragment based drug design represents a promising drug discovery paradigm complimentary to the traditional HTS based lead generation strategy. How to link fragment structures to increase compound affinity is remaining a challenge task in this paradigm. Hereby a novel deep generative model (AutoLinker) for linking fragments is developed with the potential for applying in the fragment-based lead generation scenario. The state-of-the-art transformer architecture was employed to learn the linker grammar and generate novel linker. Our results show that, given starting fragments and user customized linker constraints, our AutoLinker model can design abundant drug-like molecules fulfilling these constraints and its performance was superior to other reference models. Moreover, several examples were showcased that AutoLinker can be useful tools for carrying out drug design tasks such as fragment linking, lead optimization and scaffold hopping.

Automated, Accurate, and Scalable Relative Protein-Ligand Binding Free Energy Calculations using Lambda Dynamics

2020 ◽  
Author(s):  
E. Prabhu Raman ◽  
Thomas J. Paul ◽  
Ryan L. Hayes ◽  
Charles L. Brooks III
Keyword(s):  
Free Energy ◽  
Ligand Binding ◽  
Binding Affinity ◽  
Binding Free Energy ◽  
Computational Cost ◽  
Combinatorial Libraries ◽  
Free Energy Calculations ◽  
Lead Optimization ◽  
Efficient Estimation ◽  
Lead Compound

<p>Accurate predictions of changes to protein-ligand binding affinity in response to chemical modifications are of utility in small molecule lead optimization. Relative free energy perturbation (FEP) approaches are one of the most widely utilized for this goal, but involve significant computational cost, thus limiting their application to small sets of compounds. Lambda dynamics, also rigorously based on the principles of statistical mechanics, provides a more efficient alternative. In this paper, we describe the development of a workflow to setup, execute, and analyze Multi-Site Lambda Dynamics (MSLD) calculations run on GPUs with CHARMm implemented in BIOVIA Discovery Studio and Pipeline Pilot. The workflow establishes a framework for setting up simulation systems for exploratory screening of modifications to a lead compound, enabling the calculation of relative binding affinities of combinatorial libraries. To validate the workflow, a diverse dataset of congeneric ligands for seven proteins with experimental binding affinity data is examined. A protocol to automatically tailor fit biasing potentials iteratively to flatten the free energy landscape of any MSLD system is developed that enhances sampling and allows for efficient estimation of free energy differences. The protocol is first validated on a large number of ligand subsets that model diverse substituents, which shows accurate and reliable performance. The scalability of the workflow is also tested to screen more than a hundred ligands modeled in a single system, which also resulted in accurate predictions. With a cumulative sampling time of 150ns or less, the method results in average unsigned errors of under 1 kcal/mol in most cases for both small and large combinatorial libraries. For the multi-site systems examined, the method is estimated to be more than an order of magnitude more efficient than contemporary FEP applications. The results thus demonstrate the utility of the presented MSLD workflow to efficiently screen combinatorial libraries and explore chemical space around a lead compound, and thus are of utility in lead optimization.</p>

Nitroxyl Modified Tobacco Mosaic Virus as a Metal-Free High-Relaxivity MRI and EPR Active Superoxide Sensor

2018 ◽  
Author(s):  
Madushani Dharmarwardana ◽  
André F. Martins ◽  
Zhuo Chen ◽  
Philip M. Palacios ◽  
Chance M. Nowak ◽  
...  
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Single Molecule ◽  
Biological Fluids ◽  
Cellular Respiration ◽  
Organic Radical ◽  
Paramagnetic Resonance ◽  
Metal Free ◽  
Disease States

Superoxide overproduction is known to occur in multiple disease states requiring critical care yet non-invasive detection of superoxide in deep tissue remains a challenge. Herein, we report a metal-free magnetic resonance imaging (MRI) and electron paramagnetic resonance (EPR) active contrast agent prepared by “click conjugating” paramagnetic organic radical contrast agents (ORCAs) to the surface of tobacco mosaic virus (TMV). While ORCAs are known to be reduced <i>in vivo</i> to an MRI/EPR silent state, their oxidation is facilitated specifically by reactive oxygen species—in particular superoxide—and are largely unaffected by peroxides and molecular oxygen. Unfortunately, single molecule ORCAs typically offer weak MRI contrast. In contrast, our data confirm that the macromolecular ORCA-TMV conjugates show marked enhancement for <i>T<sub>1</sub></i> contrast at low field (<3.0 T), and <i>T<sub>2</sub></i> contrast at high field (9.4 T). Additionally, we demonstrated that the unique topology of TMV allows for “quenchless fluorescent” bimodal probe for concurrent fluorescence and MRI/EPR imaging, which was made possible by exploiting the unique inner and outer surface of the TMV nanoparticle. <a>Finally, we show TMV-ORCAs do not respond to normal cellular respiration, minimizing the likelihood for background, yet still respond to enzymatically produced superoxide in complicated biological fluids like serum.</a>

Sign in / Sign up

Export Citation Format

Share Document