Quicker and slicker: An efficient metal-free 1,3-dipolar cycloaddition of dibenzocyclooctynes with nitrones proceeded rate constants up to 39 M−1 s−1, or 300 times faster than similar reactions azides. This strategy is useful for the site-specific N-terminal modification peptides proteins (see scheme). The bioorthogonal chemical reporter emerging as a versatile method labeling biomolecules, such nucleic acids, lipids, carbohydrates, proteins.1 In this approach, an abiotic functionality...

Societal Impact Statement Infestation by the parasitic plant Striga hermonthica is a severe threat to food security in sub‐Saharan Africa, impacting production of major staple crops pearl millet and sorghum, equating 7–10 billion $ losses. Using seed dependency on host‐released germination stimulants, we have developed validated method for addressing problem accumulated parasite seedbanks—the obstacle combating infestation African rain‐fed fields. Application our promises alleviate posed...

With increasing numbers of chemicals used in modern society, assessing human and environmental exposure to them is becoming increasingly difficult. Recent advances wastewater-based epidemiology enable valuable insights into public data-poor compounds. However, measuring all >26,000 registered under REACH not just technically unfeasible but would also be incredibly expensive. In this paper, we argue that estimating emissions based on usage data could offer a more comprehensive, systematic...

Palladium-catalyzed regio- and enantioselective addition of azole heterocycles to alkoxyallenes was developed (up 92% yields up 94% ee). DFT calculations suggest a new Pd(0)-driven mechanistic pathway proceeding through protonation the Pd-coordinated allene (4-PdL2), which develops strongly nucleophilic character at central C atom.

Schnell und zielsicher: Für die metallfreie 1,3-dipolare Cycloaddition von Dibenzocyclooctinen mit Nitronen wurden Geschwindigkeitskonstanten bis 39 M−1 s−1 ermittelt, sodass diese Reaktion zu 300-mal schneller abläuft als ähnliche Reaktionen Aziden. Die Strategie ist nützlich für ortsspezifische N-terminale Modifizierung Peptiden Proteinen. The bioorthogonal chemical reporter strategy is emerging as a versatile method for the labeling of biomolecules, such nucleic acids, lipids,...

Two conformationally restricted three-dimensional aminoketone scaffolds have been synthesized in only three steps, using a continuous flow photochemistry approach, which is also amenable to scale-up. In addition, several approaches further derivatize these for the synthesis of low molecular weight compound libraries detailed.

Novel click chemistry using SPAAC and SPOCQ in tandem efficiently provides dual-labelled antibody–drug–dye conjugates.

By using supported Cu(<sc>ii</sc>) catalysts for the regioselective synthesis of 1,4-disubstituted pyrazoles, we significantly reduced Cu loading to 30 mol% and alkyne required. Also, continuous flow allowed a dramatic reduction reaction times going from 16 h residence 5–15 min, being able easily scale up this methodology.

Trifluoromethyl vinyl sulfide, a potential building block for pharmaceutically and agrochemically relevant products, is prepared used the first time in high-pressure-mediated 1,3-dipolar cycloaddition reactions with nitrones to synthesize (trifluoromethyl)sulfanyl isoxazolidines.

A new tandem strategy based on a Mannich/Pictet–Spengler sequence has been developed and applied to the synthesis of small library (14 examples) privileged compounds spiro[piperidine‐pyridoindole] core. The proceeds by diastereoselective Pictet–Spengler cyclization after condensation several tryptamine derivatives with three novel piperidin‐4‐ones containing fluorinated substituents F, CF 3 SF 5 . were synthesized from readily available starting materials an enantioselective multi‐component...

[reaction: see text] The dipolarophilic reactivity of enantiopure (Z)-3-p-tolylsulfinylacrylonitriles (1) has been evaluated with diazoalkanes. 3-Cyanopyrazoles are obtained when R = H, but alkyl (Bn, n-Bu, and t-Bu) only one cycloadduct (4 or 5) is formed in high yield under mild conditions, therefore evidencing a complete control the regioselectivity endo/exo pi-facial selectivities. These reactions new straightforward entry to synthesis pyrazolines related structures reveal excellent...

The synthesis of a small library dihydrouracils spiro-fused to pyrrolidines is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, structural feature often encountered in active central nervous system. b-aryl through three-step methodology that includes Knoevenagel condensation reaction, 1,3-dipolar cycloaddition and nitrile reduction.

Abstract While continuous-flow chemistry is steadily increasing its footprint in academic research and the manufacturing of pharmaceutical intermediates fine chemicals, attention for flow educational programs on average rather limited. This account meant to provide a personal overview possibilities address involvement various stages chemical education.

The recent success of fragment-based drug discovery (FBDD) is inextricably linked to adequate library design. To guide the design our fragment libraries, we have constructed an automated workflow in open-source KNIME software. considers chemical diversity and novelty fragments, can also take into account three-dimensional (3D) character. This tool be used create large diverse libraries but select a small number representative compounds as focused set unique screening enrich existing...

Abstract Cyclobutanes are attracting a growing interest in medicinal chemistry because of their unique structure and potentially advantageous pharmacological properties. Specifically, 1,3‐disubstituted cyclobutanes have been explored as conformationally restricted propyl isosteres drug development. In this study, concise two‐diversification‐point library 3‐amino‐3‐[(arenesulfonyl)methyl]cyclobutanols was synthesized through hyperbaric [2+2] cycloaddition reaction between sulfonyl allenes...

The synthesis of a 144-compound library hydantoins and thiohydantoins spiro-fused to pyrrolidines is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, structural feature often encountered in active central nervous system. All possible stereoisomers two-stereocenter synthesized. 80-membered hydantoin sublibrary was obtained yields ranging 58 100% (87% average) purities 51 64-membered thiohydantoin 65 (89% 67 (93% average).

Abstract A new method for rapid larger‐scale production of trans ‐cyclooctenes (TCOs) in continuous flow was developed: Up to 2.2 g/h specific TCOs can be produced by using this procedure. This utilizes the classical photoisomerization cis (CCOs) synthesis but substitutes conventionally used silver nitrate impregnated silica gel column a liquid−liquid extraction module. In addition, provides possibility external addition substrate scale up and speed because concentration CCO is kept...

The nomenclature of cations R1C(=O+R3)R2 (R1, R2, R3 = H or organyl) has been examined and shown to be in a state immeasurable confusion: pragmatic recommendation is made that the generic term "carbonylonium ions" should adopted for these intermediates, which comprises terms "aldehydium" (R1 H, "ketonium R2 organyl, corresponding aldehyde- ketone-based respectively.

Abstract The click reaction between a functionalized trans ‐cyclooctene (TCO) and tetrazine (Tz) is compelling method for bioorthogonal conjugation in combination with payload releasing capabilities. However, the synthesis of difunctionalized TCOs remains challenging. As result, these compounds are poorly accessible, which impedes development novel applications. In this work, scalable accessible new TCO reported only four single selective high yielding steps starting from commercially...

A structurally diverse library of potentially pharmacologically important compounds employing classical synthesis methods is described. These are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in active central nervous system. Tri- and tetracyclic scaffolds were obtained using Pictet-Spengler reaction, resulting hexahydropyrrolo[3,4-c]isoquinolines 1-3, an octahydropyrrolo[3',4':5,6]pyrido[3,4-b]indole 4,...