Aromatic rings are found in a wide variety of products, including pharmaceuticals, agrochemicals, and functional materials. Diaryliodonium salts are new reagents used to transfer aryl groups under ...both metal‐free and metal‐catalyzed reactions and thereby synthesize arene‐containing compounds. This minireview focuses on recent studies in selective aryl transfer reactions from unsymmetrical diaryliodonium salts under metal‐free conditions. Reactions reported from 2007 to 2017, which represents a period of significant growth in diaryliodonium salt chemistry, are presented and organized by the type of reactive intermediate formed in the reaction. Specifically, reactions involving λ3‐iodane, λ3‐iodane radical anions, aryl radicals, and arynes are discussed. Chemoselectivity trends in aryl transfer are compared and contrasted across reaction intermediates and translation to potential auxiliaries are posited.
How I gives it away: Diaryliodonium salts are new arylation reagents that participate in diverse chemical transformations. Aryl transfer selectivity from unsymmetrical diaryliodonium salts is examined and organized by the type of reactive intermediate that is formed in the reaction. Electronic and steric effects of the aryl groups are the dominant controlling factors for selective aryl transfer (see scheme).
Catalytic Cross-Coupling of Unactivated Arenes Stuart, David R; Fagnou, Keith
Science (American Association for the Advancement of Science),
05/2007, Volume:
316, Issue:
5828
Journal Article
Peer reviewed
The industrially important coupling of aromatic compounds has generally required differential prefunctionalization of the arene coupling partners with a halide and an electropositive group. Here we ...report that palladium, in conjunction with a copper oxidant, can catalyze the cross-coupling of N-acetylindoles and benzenes in high yield and high regioselectivity across a range of indoles without recourse to activating groups. These reactions are completely selective for arene cross-coupling, with no products arising from indole or benzene homo-coupling detected by spectroscopic analysis. This efficient reactivity should be useful in the design of other oxidative arene cross-couplings as well.
Practical Data Science for Information Professionals provides an accessible introduction to a potentially complex field, providing readers with an overview of data science and a framework for its ...application. It provides detailed examples and analysis on real data sets to explore the basics of the subject in three principle areas: clustering and social network analysis; predictions and forecasts; and text analysis and mining. As well as highlighting a wealth of user-friendly data science tools, the book also includes some example code in two of the most popular programming languages ( R and Python ) to demonstrate the ease with which the information professional can move beyond the graphical user interface and achieve significant analysis with just a few lines of code. After reading, readers will understand: · the growing importance of data science · the role of the information professional in data science · some of the most important tools and methods that information professionals can use. Bringing together the growing importance of data science and the increasing role of information professionals in the management and use of data, Practical Data Science for Information Professionals will provide a practical introduction to the topic specifically designed for the information community. It will appeal to librarians and information professionals all around the world, from large academic libraries to small research libraries. By focusing on the application of open source software, it aims to reduce barriers for readers to use the lessons learned within.
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains ...have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
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•Despite similar RBD mutations, P.1 is easier to neutralize than B.1.351•P.1, B.1.351, and B.1.1.7 partially or fully escape most VH3-53 antibodies•mAb 222 (VH3-53) retains neutralization against all three variants•Neutralization is restored in VH3-53 chimeric antibodies with mAb 222 LC
Structural and functional analysis of the P.1 variant of SARS-CoV-2 from Brazil reveals less resistance to antibodies generated from natural infection or vaccination compared to another similar variant, B.1.351. A monoclonal antibody, mAb 222, is able to neutralize all three variants (P.1, B.1.351, and B.1.1.7), with its light chain able to restore neutralization potency to a broad group of antibodies.
There are as yet no licensed therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric spike whose receptor binding domain (RBD) recognizes ...angiotensin-converting enzyme 2, initiating conformational changes that drive membrane fusion. We find that the monoclonal antibody CR3022 binds the RBD tightly, neutralizing SARS-CoV-2, and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilizing CR3022 epitope is inaccessible in the prefusion spike, suggesting that CR3022 binding facilitates conversion to the fusion-incompetent post-fusion state. Cryogenic electron microscopy (cryo-EM) analysis confirms that incubation of spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope could be useful therapeutically, possibly in synergy with an antibody that blocks receptor attachment.
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•CR3022 binds the RBD of SARS-CoV-2 and shows strong neutralization•Neutralization is by destroying the prefusion spike conformation•CR3022 binds a highly conserved epitope that is inaccessible in prefusion spike protein•CR3022 could have therapeutic potential alone or in synergy with a receptor blocker
Huo et al. find that the antibody CR3022 binds tightly to the receptor binding domain of the SARS-CoV-2 spike at a site different to that used by the receptor. CR3022 effectively neutralizes the virus, and cryo-EM reveals that it disrupts the spike. Such antibodies could have potential as COVID-19 therapeutics.
Arenes are broadly found motifs in societally important molecules. Access to diverse arene chemical space is critically important, and the ability to do so from common reagents is highly desirable. ...Aryl(TMP)iodonium tosylates provide one such access point to arene chemical space via diverse aryl intermediates. Here we demonstrate that controlling reaction pathways selectively leads to arynes with a broad scope of arenes and arynophiles (24 examples, 70% average yield) and efficient access to biologically active compounds.
By changing the stoichiometric oxidant and modifying the indole N-substituent in palladium-catalyzed oxidative arene cross-coupling reactions, both C2 and C3 oxidative indole arylation can be ...achieved in high yield. High regioselectivity can also be achieved with the benzene component, and the use of this methodology with pyrrole substrates is illustrated. A mechanistic hypothesis for the change in C2/C3 selectivity is advanced.
A mild and metal‐free approach to C−N coupling is described that employs diaryliodonium salt electrophiles and secondary aliphatic amine nucleophiles. This reaction results in direct ...ipso‐substitution of the iodonium moiety and unsymmetrical aryl(TMP)iodonium salts are primarily employed. Moreover, arene substituents and substitution patterns that currently pose a challenge to classical metal‐free methods are accommodated and the alicyclic amine nucleophiles used here are unprecedented in other contemporary metal‐free C−N coupling reactions.
A new challenger: Aryl amines are synthesized in a metal‐free reaction between unsymmetrical aryl(2,4,6‐trimethoxyphenyl)iodonium salt electrophiles and alicyclic amine nucleophiles. Yields and scope exceed those of the classical SNAr approach. The reaction conditions are mild and lead to highly regiospecific substitution of the iodonium moiety in the iodonium reagents.
Recently, the rhodium(III)-complex Cp*RhCl22 1 has provided exciting opportunities for the efficient synthesis of aromatic heterocycles based on a rhodium-catalyzed C−H bond functionalization event. ...In the present report, the use of complexes 1 and its dicationic analogue Cp*Rh(MeCN)3SbF62 2 have been employed in the formation of indoles via the oxidative annulation of acetanilides with internal alkynes. The optimized reaction conditions allow for molecular oxygen to be used as the terminal oxidant in this process, and the reaction may be carried out under mild temperatures (60 °C). These conditions have resulted in an expanded compatibility of the reaction to include a range of new internal alkynes bearing synthetically useful functional groups in moderate to excellent yields. The applicability of the method is exemplified in an efficient synthesis of paullone 3, a tetracyclic indole derivative with established biological activity. A mechanistic investigation of the reaction, employing deuterium labeling experiments and kinetic analysis, has provided insight into issues of reactivity for both coupling partners as well as aided in the development of conditions for improved regioselectivity with respect to meta-substituted acetanilides. This reaction class has also been extended to include the synthesis of pyrroles. Catalyst 2 efficiently couples substituted enamides with internal alkynes at room temperature to form trisubstituted pyrroles in good to excellent yields. The high functional group compatibility of this reaction enables the elaboration of the pyrrole products into a variety of differentially substituted pyrroles.
We investigated determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer–BioNTech or ...Oxford–AstraZeneca vaccines.
HCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/mL). We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time.
3570/3610 HCWs (98.9%) were seropositive >14 days post first vaccination and prior to second vaccination: 2706/2720 (99.5%) were seropositive after the Pfizer–BioNTech and 864/890 (97.1%) following the Oxford–AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection: median (IQR) >21 days post first Pfizer–BioNTech 14 604 (7644–22 291) AU/mL versus 1028 (564–1985) AU/mL without prior infection (p < 0.001). Oxford–AstraZeneca vaccine recipients had lower readings post first dose than Pfizer–BioNTech recipients, with and without previous infection, 10 095 (5354–17 096) and 435 (203–962) AU/mL respectively (both p < 0.001 versus Pfizer–BioNTech). Antibody responses >21 days post second Pfizer vaccination in those not previously infected, 10 058 (6408–15 582) AU/mL, were similar to those after prior infection followed by one vaccine dose.
SARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.
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