SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules. This review discusses the growing ...number of applications of SuFEx, which can be found in nearly all areas of modern chemistry; from drug discovery to materials science.
Sulfur fluoride exchange (SuFEx) has emerged as the new generation of click chemistry. We report here a SuFEx-enabled, agnostic approach for the discovery and optimization of covalent inhibitors of ...human neutrophil elastase (hNE). Evaluation of our ever-growing collection of SuFExable compounds toward various biological assays unexpectedly revealed a selective and covalent hNE inhibitor: benzene-1,2-disulfonyl fluoride. Synthetic derivatization of the initial hit led to a more potent agent, 2-(fluorosulfonyl)phenyl fluorosulfate with IC50 0.24 μM and greater than 833-fold selectivity over the homologous neutrophil serine protease, cathepsin G. The optimized, yet simple benzenoid probe only modified active hNE and not its denatured form.
Diversity Oriented Clicking (DOC) is a unified click‐approach for the modular synthesis of lead‐like structures through application of the wide family of click transformations. DOC evolved from the ...concept of achieving “diversity with ease”, by combining classic C−C π‐bond click chemistry with recent developments in connective SuFEx‐technologies. We showcase 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluorides (SASFs) as a new class of connective hub in concert with a diverse selection of click‐cycloaddition processes. Through the selective DOC of SASFs with a range of dipoles and cyclic dienes, we report a diverse click‐library of 173 unique functional molecules in minimal synthetic steps. The SuFExable library comprises 10 discrete heterocyclic core structures derived from 1,3‐ and 1,5‐dipoles; while reaction with cyclic dienes yields several three‐dimensional bicyclic Diels–Alder adducts. Growing the library to 278 discrete compounds through late‐stage modification was made possible through SuFEx click derivatization of the pendant sulfonyl fluoride group in 96 well‐plates—demonstrating the versatility of the DOC approach for the rapid synthesis of diverse functional structures. Screening for function against MRSA (USA300) revealed several lead hits with improved activity over methicillin.
Diversity‐oriented clicking (DOC) is a unified click chemistry approach for the synthesis of diverse lead‐like structures. Herein DOC is showcased through the application of novel highly activated2‐substituted‐alkynyl‐1‐sulfonyl fluoride (SASF) hubs in combination with a range of selective and robust click cycloaddition reactions, delivering an unprecedented SuFExable library of functional biologically active lead structures.
Cathode R&D for future light sources Dowell, D.H.; Bazarov, I.; Dunham, B. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2010, Letnik:
622, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper reviews the requirements and current status of cathodes for accelerator applications, and proposes a research and development plan for advancing cathode technology. Accelerator cathodes ...need to have long operational lifetimes and produce electron beams with a very low emittance. The two principal emission processes to be considered are thermionic and photoemission with the photocathodes being further subdivided into metal and semi-conductors. Field emission cathodes are not included in this analysis. The thermal emittance is derived and the formulas used to compare the various cathode materials. To date, there is no cathode which provides all the requirements needed for the proposed future light sources. Therefore a three part research plan is described to develop cathodes for these future light source applications.
The boom in growth of 1,4‐disubstituted triazole products, in particular, since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the CuI‐catalyzed ...azide–alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1‐substituted‐1,2,3‐triazoles has been surprisingly more challenging. Reported here is a straightforward and scalable click‐inspired protocol for the synthesis of 1‐substituted‐1,2,3‐triazoles from organic azides and the bench stable acetylene surrogate ethenesulfonyl fluoride (ESF). The new transformation tolerates a wide selection of substrates and proceeds smoothly under metal‐free conditions to give the products in excellent yield. Under controlled acidic conditions, the 1‐substituted‐1,2,3‐triazole products undergo a Michael addition reaction with a second equivalent of ESF to give the unprecedented 1‐substituted triazolium sulfonyl fluoride salts.
A metal‐free click protocol for the synthesis of 1‐substituted 1,2,3‐triazoles from organic azides and ethenesulfonyl fluoride (ESF) is described. The synthetic value of the concerted reaction is reflected in the simplicity of the protocol and demonstrated by the one‐pot preparation of the triazoles on gram scale. The utility of this method is shown in the late‐stage modification of several drugs, including the antibiotic chloramphenicol, giving rise a new active antibiotic derivative.
We demonstrate 1,2-dibromoethane-1-sulfonyl fluoride (DESF) as a bench-stable and readily accessible precursor to the robust SuFEx connector, 1-bromoethene-1-sulfonyl fluoride (BESF). The in situ ...generation of BESF from DESF opens up several new reaction profiles, including application in the syntheses of unprecedented 3-substituted isoxazole-5-sulfonyl fluorides, 1-substituted-1H-1,2,3-triazole-4-sulfonyl fluorides, 2-amino-1-bromoethane-1-sulfonyl fluorides and 4-bromo-β-sultams in good to excellent yields. These new modules comprise a pendant sulfonyl fluoride handle, which further undergoes facile and selective SuFEx reactions with a selection of aryl silyl ethers to generate stable and useful sulfonate connections.
A novel series of addition reactions of highly reactive 2-substituted-alkynyl-1-sulfonyl fluoride (SASF) hubs with DMSO and DMF for the synthesis of two unique sulfonyl fluoride cores is described. ...The stereoselective chemistry allowed the unprecedented syntheses of 12 (
Z
)-2-(dimethylsulfonio)-2-(fluorosulfonyl)-1-substitutedethen-1-olates and 10 (
E
)-1-(dimethylamino)-3-oxo-3-substitutedprop-1-ene-2-sulfonyl fluorides from DMSO and DMF, respectively. The reactions proceed expediently to give single products in excellent yield without the need for chromatographic purification. Furthermore, the utility of the DMSO derived products is demonstrated in the synthesis of synthetically valuable β-keto sulfonyl fluorides under hydrogenation conditions in excellent yields.
A novel series of addition reactions for the synthesis of two highly-functionalised sulfonyl fluoride containing olefins from 2-substituted-alkynyl-1-sulfonyl fluorides using a diversity oriented clicking strategy.
The aim of strabismus surgery is to improve alignment and ideally restore binocular vision. Prism adaptation (PAT) in esotropia is known to improve post-operative outcomes by allowing choice of ...target angle in line with pre-operative fusion potential. Reaching a successful end-point in PAT requires co-operation, which is not a given in the paediatric population. The purpose of this study is to describe the successful use of prism adaptation in children in planning target angles for esotropia surgery. Retrospective review of 29 cases from a tertiary centre was conducted, including cases who underwent PAT prior to esotropia surgery over a 6-year period (Jan 2016- Jan 2023). Data was collected from the electronic patient record including patient age, diagnosis, measurements of presenting and prism adapted angles, surgery performed and surgical outcomes. Successful prism adaptation was carried out in children of ages 3-16 . The average presenting angle of esodeviation was 20.9 PD in the distance and 27.3 PD at near. The average maximum prism adapted angle, which was the target angle used for surgery, was 35.3 PD (range 25-50PD). All patients underwent bimedial recessions except one, a re-do who underwent LR re-advancement. 3 patients had one LR resection in addition (3/28). 89.7% of patients achieved binocular vision with stereopsis, 3.4% achieved binocular vision with simultaneous perception. 2 patients had no demonstrable BV, neither were overcorrected post-operatively. Pre-operative PAT is an effective tool in pre-operative assessment of paediatric esotropia patients with binocular potential and can be used to optimise surgical planning and outcomes.
Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and ...pharmaceutically important drugs. We report here the development of “SuFExAmide”: a new sulfur–fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene‐1,3‐disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron‐deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.
The perfect couple: A new SuFEx (sulfur–fluoride exchange) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates, using benzene‐1,3‐disulfonyl fluoride as a condensing reagent. SuFExAmide has broad substrate scope and is well suited for the synthesis of challenging, sterically hindered and electron‐deficient secondary and tertiary amides. The majority of the 44 examples of amide products described here were obtained in high yield without the need for excess reagents or chromatographic purification.
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