A stepwise huisgen cycloaddition process: copper(I)-catalyzed regioselective "ligation" of azides and terminal alkynes.

Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

/pdf/self-assembled-monolayers-of-thiolates-on-metals-as-a-form-1neb0hj3k4.pdf

Self-assembled monolayers of thiolates on metals as a form of nanotechnology.

Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors. Traditional inflammation and pain relief drugs target both cyclooxygenase 1 and 2 (COX-1 and COX-2), causing severe side effects. Here, the authors use in situ click chemistry to develop COX-2 specific inhibitors with high in vivo anti-inflammatory activity.

/pdf/in-situ-click-chemistry-generation-of-cyclooxygenase-2-zyy8rhnlnx.pdf

In situ click chemistry generation of cyclooxygenase-2 inhibitors

3.2.3. Hydroformylation 2467 3.2.4. Dimerization 2468 3.2.5. Oxidative Cleavage and Ozonolysis 2469 3.2.6. Metathesis 2470 4. Terpenes 2472 4.1. Pinene 2472 4.1.1. Isomerization: R-Pinene 2472 4.1.2. Epoxidation of R-Pinene 2475 4.1.3. Isomerization of R-Pinene Oxide 2477 4.1.4. Hydration of R-Pinene: R-Terpineol 2478 4.1.5. Dehydroisomerization 2479 4.2. Limonene 2480 4.2.1. Isomerization 2480 4.2.2. Epoxidation: Limonene Oxide 2480 4.2.3. Isomerization of Limonene Oxide 2481 4.2.4. Dehydroisomerization of Limonene and Terpenes To Produce Cymene 2481

Chemical Routes for the Transformation of Biomass into Chemicals

Katalytische asymmetrische Aminohydroxylierung mit Amino‐substituierten Heterocyclen als Stickstoffquelle

Significance The ease of diversification of 2-Substituted-Alkynyl-1-Sulfonyl Fluorides through numerous reaction pathways further validates Diversity Oriented Clicking as an effective and robust method for lead discovery; one of the fundamental goals of click chemistry. The application of this approach is showcased by the discovery of a novel class of covalent inhibitors of the human neutrophil elastase, an attractive therapeutic target due to its implication in numerous chronic diseases. These molecules provide a prime example of the Sleeping Beauty effect in action, bio-compatible SuFEx reactions mediated by environmental factors unique to the “live” protein system, securing sulfur-fluoride-containing ligands as promising covalent therapeutics.

/pdf/diversity-oriented-clicking-delivers-b-substituted-alkenyl-4186e2r2.pdf

Diversity oriented clicking delivers β-substituted alkenyl sulfonyl fluorides as covalent human neutrophil elastase inhibitors

Rhenium-catalyzed epoxidation of olefinic substrates is accelerated by the use of acclerants having a nitrogenous aromatic heterocyclic structure. Use of the accelerants also enables the use of aqueous hydrogen peroxide as an oxidant. To achieve optimum acceleration, the accelerant should have a concentration within a range from 2.0 mole percent to 100 mole percent of the acclerant with respect to 1 mole of the olefinic substrate. Use of the accelerant also results in an increased yield with respect to the conversion of the olefinic substrate to epoxide product.

Accelerated catalysis of olefinic epoxidations

A simple route to enantiomerically enriched oxazolidin-2-ones

http://www.cell.com/article/S2542435122006092/pdf

K. Barry Sharpless

Papers

Katalytische asymmetrische Aminohydroxylierung mit Amino‐substituierten Heterocyclen als Stickstoffquelle

Diversity oriented clicking delivers β-substituted alkenyl sulfonyl fluorides as covalent human neutrophil elastase inhibitors

Accelerated catalysis of olefinic epoxidations

A simple route to enantiomerically enriched oxazolidin-2-ones

High-performing polysulfate dielectrics for electrostatic energy storage under harsh conditions.