ORCID Profile
0000-0003-2162-3234
Current Organisations
Cold Spring Harbor Laboratory
,
La Trobe University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Bioprocessing, Bioproduction and Bioproducts | Organic Chemistry | Agriculture, Land and Farm Management | Medical Biochemistry and Metabolomics not elsewhere classified | Organic Chemical Synthesis | Polymers and Plastics | Inorganic Chemistry not elsewhere classified | Farm Management, Rural Management and Agribusiness
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Chemical Sciences | Plant Extracts (e.g. Pyrethrum, Alkaloids, Jojoba Oil) | Industrial Crops not elsewhere classified | Expanding Knowledge in the Biological Sciences |
Related Links
Publications
Structural Characterisation of the Apo-form of Human Lactate Dehydrogenase M Isozyme
Publisher: Worldwide Protein Data Bank
Date: 30-04-2014
DOI: 10.2210/PDB4L4R/PDB
Shapeshifting Antibiotics: Bullvalene Linked Vancomycin Dimers are Effective Against Multidrug-Resistant Gram-Positive Bacteria
Publisher: American Chemical Society (ACS)
Date: 21-04-2022
DOI: 10.26434/CHEMRXIV-2022-H2PDS
Abstract: The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA) as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a click-linked bullvalene core, hence exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding D-Ala-D-Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, inferring the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.
Review on some antioxidant plants growing in Arab world
Publisher: Elsevier BV
Date: 10-2011
CCDC 203123: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6TCCQ
CCDC 200559: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPN7
Total synthesis of the epoxyquinol dimer (+)-panepophenanthrin: application of a diastereospecific biomimetic Diels–Alder dimerisation
Publisher: Elsevier BV
Date: 10-2006
Biocompatible SuFEx Click Chemistry: Thionyl Tetrafluoride (SOF4)‐Derived Connective Hubs for Bioconjugation to DNA and Proteins
Publisher: Wiley
Date: 08-05-2019
Chemoselective Palladium-Catalyzed Cyanation of Alkenyl Halides
Publisher: American Chemical Society (ACS)
Date: 27-03-2014
DOI: 10.1021/OL500618W
Abstract: A palladium-catalyzed cyanation of alkenyl halides using acetone cyanohydrin is described. A number of structurally erse alkenylic nitrile containing compounds was prepared in one step under optimized conditions. The reaction proved to be efficient, chemoselective, easy to perform, and tolerant of a number of functional groups.
Microwave-Enhanced Reaction of Thioacids with Azides in Aqueous Medium
Publisher: Georg Thieme Verlag KG
Date: 13-09-2011
Metal-Free Click Synthesis of Functional 1-Substituted-1,2,3-Triazoles
Publisher: American Chemical Society (ACS)
Date: 15-10-2019
DOI: 10.26434/CHEMRXIV.9937754.V1
Abstract: The 1,2,3-triazole group is one of the most important connective linkers and functional aromatic heterocycles in modern chemistry. The boom in growth of, in particular, 1,4-disubstituted triazole products since the early 2000’s, can be largely attributed to the birth of click chemistry and the discovery of the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Yet the synthesis of relatively simple, albeit important, 1-substituted-1,2,3-triazoles, has been surprisingly more challenging. We report a straightforward and scalable click-protocol for the synthesis of 1-substituted-1,2,3-triazoles from organic azides and the bench stable acetylene-surrogate, ethenesulfonyl fluoride (ESF). The transformation proceeds through a thermal 1,3-dipolar cycloaddition of the azide and ESF to give a sulfonyl fluoride substituted triazoline, that itself spontaneously aromatizes through formal loss of HF/SO 2 to give the stable triazole products with excellent fidelity. The new click reaction tolerates a wide selection of substrates and proceeds smoothly under metal-free conditions to give the products in excellent yield, and without need for additives or chromatographic purification. Further, under controlled conditions, the 1-substituted-1,2,3-triazole products undergo Michael reaction with a second equivalent of ESF to give the unprecedented 1-substituted triazolium sulfonyl fluoride salts, demonstrating the versatility and orthogonal reactivity of ESF. The importance of this novel method is evidenced through the late-stage modification of several drugs and drug fragments, including the synthesis of a new improved derivative of the famous antibiotic, chlor henicol.
Efficient conversion of aromatic amines into azides: A one-pot synthesis of triazole linkages
Publisher: American Chemical Society (ACS)
Date: 29-03-2007
DOI: 10.1021/OL070527H
Abstract: [reaction: see text] An efficient and improved procedure for the preparation of aromatic azides and their application in the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition ("click reaction") is described. The synthesis of aromatic azides from the corresponding amines is accomplished under mild conditions with tert-butyl nitrite and azidotrimethylsilane. 1,4-Disubstituted 1,2,3-triazoles were obtained in excellent yields from a variety of aromatic amines without the need for isolation of the azide intermediates.
Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane‐Spanning Protein
Publisher: Wiley
Date: 20-10-2017
CCDC 200553: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPG1
Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs
Publisher: Wiley
Date: 04-06-2020
Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
Publisher: Wiley
Date: 27-02-2019
Abstract: SuFEx is a new-generation click chemistry transformation that exploits the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx-based procedure for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new process involves rapid S-F exchange with trifluoromethyltrimethylsilane (TMSCF
An improved synthesis of 1,2-benzisoxazoles: TBAF mediated 1,3-dipolar cycloaddition of nitrile oxides and benzyne
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/B922489K
Abstract: An efficient synthesis of a range of 1,2-benzisoxazoles using an improved 1,3-dipolar cycloaddition of nitrile oxides and benzyne is described. Key to the procedure is the in situ generation of the reactive nitrile oxide and benzyne reaction partners mediated by TBAF. Reactions are complete within 30 s, giving the target products in good to excellent yield.
A synthetic approach to kingianin A based on biosynthetic speculation
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C1CC13949E
Abstract: A synthetic approach towards the structurally complex dimer, kingianin A is reported. The strategy involved a cascade of complexity generating reactions, inspired through biosynthetic speculation. A concise protecting group free synthesis of the proposed monomeric precursor pre-kingianin A has been achieved using a tandem Stille cross-coupling reaction and electrocyclisation process. However, preliminary studies of the key dimerisation reaction have been conducted, which indicate that the process is not spontaneous, raising questions as to the origin of this complex natural product.
A short total synthesis of aureothin and N-acetylaureothamine
Publisher: American Chemical Society (ACS)
Date: 21-01-2005
DOI: 10.1021/OL047594L
Abstract: The total synthesis of the nitrophenyl pyrones, (+/-)-aureothin and (+/-)-N-acetylaureothamine, starting from known 2-ethyl-6-methoxy-3,5-dimethyl-4H-pyran-4-one are described. The key steps involved in the synthesis are the construction of the tetrahydrofuran motif using a palladium-catalyzed cycloaddition and the ruthenium-catalyzed cross-metathesis reaction of an alkenyl boronic ester. [reaction: see text]
Metal‐Free Synthesis of Functional 1‐Substituted‐1,2,3‐Triazoles from Ethenesulfonyl Fluoride and Organic Azides
Publisher: Wiley
Date: 28-11-2020
Abstract: 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 Cu I ‐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.
Aminium cation-radical catalysed selective hydration of (E)-aryl enynes
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1CC02257A
Abstract: A new selective method for the mild and metal-free catalytic Markovnikov hydration of ( E )-aryl enynes to the corresponding enones, mediated through the bench-stable aminium salt, tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBPA), is reported.
5 Sulfur Fluoride Exchange (SuFEx)
Publisher: Georg Thieme Verlag KG
Date: 2022
Abstract: Sulfur Fluoride Exchange (SuFEx) click chemistry is a new generation technology for creating stable molecular connections with absolute reliability under metal-free conditions. SuFEx builds upon the fundamental principles of click chemistry by exploiting a unique blend of stability and latent reactivity of high oxidation state sulfur fluoride [e.g., S(VI)] functionalities to forge stable covalent linkages at connective SuFEx hubs. In this review, we focus mainly on the SuFEx hubs, sulfuryl fluoride (SO2F2), thionyl tetrafluoride (SOF4), ethenesulfonyl fluoride (ESF), 1-bromoethene-1-sulfonyl fluoride (BESF) and, 2-substituted alkyne-1-sulfonyl fluorides (SASFs). We describe each connector’s unique reactivity and their application to SuFEx click chemistry.
Tuneable DNA-based asymmetric catalysis using a G-quadruplex supramolecular assembly
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0CC00194E
Abstract: Described is the first modular construction of a G-quadruplex chiral catalyst. The key objective was to use G-quadruplex structures to act as chiral ligands that would allow access to either enantiomer of the product of a Diels-Alder reaction.
The isolation and chemistry of tantalum dimethylamides containing resolved 3,3 '-disubstituted-1,1 '-bi-2,2 '-naphthoxide ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 10-03-2003
DOI: 10.1039/B212910H
Sulfur-Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates
Publisher: Wiley
Date: 26-07-2017
Abstract: 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.
SuFEx Chemistry of Thionyl Tetrafluoride (SOF4) with Organolithium Nucleophiles: Synthesis of Sulfonimidoyl Fluorides, Sulfoximines, Sulfonimidamides, and Sulfonimidates
Publisher: Wiley
Date: 16-01-2018
G-quadruplex compounds and cis-platin act synergistically to inhibit cancer cell growth in vitro and in vivo
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.BCP.2009.03.018
Abstract: The ability of two structurally erse telomeric G-quadruplex-binding compounds to synergise the action of cis-platin has been investigated in two cancer cell lines. One compound is a trisubstituted acridine compound AS1410, a close analogue of BRACO-19, and the other is a non-polycyclic compound synthesised using click chemistry and containing two triazole rings. Both compounds produce growth arrest at sub-cytotoxic concentrations in the two cell lines (MCF7 and A549), with behaviour consistent with telomere targeting mechanisms. Synergistic behaviour was observed in both cell lines with both compounds in combination with cis-platin, but only when the ratio of AS1410:cis-platin is >1. In vivo tumour xenograft studies with the A549 lung cancer model and the trisubstituted acridine compound AS1410 showed only a modest anti-tumour effect when administered alone, but produced rapid and highly significant decreases in tumour volume when administered in combination with cis-platin.
Stabilization of G-Quadruplex DNA by Highly Selective Ligands via Click Chemistry
Publisher: American Chemical Society (ACS)
Date: 12-2006
DOI: 10.1021/JA0661919
Abstract: A series of G-quadruplex stabilizing compounds have been prepared via click chemistry employing the Cu(I)-catalyzed Huisgen reaction. These compounds were shown to bind tightly to G-quadruplex DNA even in the presence of competing high concentrations of duplex DNA. Furthermore, a modified TRAP assay has shown that some of these compounds also inhibit telomerase at low micromolar concentration.
A fragment based click chemistry approach towards hybrid G-quadruplex ligands: design, synthesis and biophysical evaluation
Publisher: Elsevier BV
Date: 2012
Frontispiece: Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs
Publisher: Wiley
Date: 13-07-2020
Continuous Flow Synthesis of Secondary Amides by Tandem Azidation-Amidation of Anilines
Publisher: Georg Thieme Verlag KG
Date: 29-05-2012
Synthesis of Sulfonyl Azides via Lewis Base Activation of Sulfonyl Fluorides and Trimethylsilyl Azide
Publisher: Georg Thieme Verlag KG
Date: 21-04-2016
Multidimensional SuFEx Click Chemistry: Sequential Sulfur(VI) Fluoride Exchange Connections of Diverse Modules Launched From An SOF4 Hub
Publisher: Wiley
Date: 06-02-2017
An efficient synthesis of cyercene A
Publisher: Elsevier BV
Date: 08-2004
CCDC 200554: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPH2
Biomimetic synthesis and structural revision of (+/-)-tridachiahydropyrone
Publisher: American Chemical Society (ACS)
Date: 22-08-2008
DOI: 10.1021/OL8015836
Abstract: A short synthesis of the revised structure of the marine natural product tridachiahydropyrone is described. A novel biomimetic photochemical electrocyclization was employed to construct the bicyclic carbon framework from an open-chain polyene precursor. The spectroscopic data matched that of the isolated natural product, supporting a revised structure of this complex metabolite.
Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs
Publisher: Wiley
Date: 04-06-2020
Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria
Publisher: Proceedings of the National Academy of Sciences
Date: 03-04-2023
Abstract: The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding d -Ala- d -Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, implying the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.
Antiulcerogenic Activities of the Extracts and Isolated Flavonoids of Euphorbia cuneata Vahl
Publisher: Wiley
Date: 24-10-2012
DOI: 10.1002/PTR.4872
Abstract: The total alcohol extracts of Euphorbia cuneata Vahl.(Euphorbiaceae) were screened for antiulcerogenic activity using an ethanol-induced ulcer model at doses of 125, 250 and 500 mg/kg. The extracts possessed antiulcerogenic activity in a dose-dependent manner. Four flavonoidal compounds were isolated and identified as naringenin, aromadendrin, apigenin and 4'-O-methoxy-luteolin-7-O-rhamnoglucoside, each demonstrating antiulcerogenic activity with curative ratios ranging from 75.78% to 88.23%. In addition, the alcohol extracts and isolated compounds were shown to scavenge the 1,1-diphenyl,2-picrylhydrazyl radical by different ratio, with the most effective being 4'-O-methoxy-luteolin-7-O-rhamnoglucoside (91.14%). The antioxidant activity of the alcohol extracts and the isolated compounds may explain the antiulcerogenic properties. No side effects were observed on either liver or kidney functions.
Diversity oriented clicking delivers beta-substituted alkenyl sulfonyl fluorides as covalent human neutrophil elastase inhibitors
Publisher: Proceedings of the National Academy of Sciences
Date: 07-09-2022
Abstract: Diversity Oriented Clicking (DOC) is a discovery method geared toward the rapid synthesis of functional libraries. It combines the best attributes of both classical and modern click chemistries. DOC strategies center upon the chemical ersification of core “SuFExable” hubs—exemplified by 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs)—enabling the modular assembly of compounds through multiple reaction pathways. We report here a range of stereoselective Michael-type addition pathways from SASF hubs including reactions with secondary amines, carboxylates, 1 H -1,2,3-triazole, and halides. These high yielding conjugate addition pathways deliver unprecedented β-substituted alkenyl sulfonyl fluorides as single isomers with minimal purification, greatly enriching the repertoire of DOC and holding true to the fundamentals of modular click chemistry. Further, we demonstrate the potential for biological function – a key objective of click chemistry – of this family of SASF-derived molecules as covalent inhibitors of human neutrophil elastase.
Accelerated SuFEx Click Chemistry For Modular Synthesis**
Publisher: Wiley
Date: 07-12-2022
Abstract: SuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S−O linkages upon exchange of S−F bonds with aryl silyl‐ether substrates, and while near‐perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2‐tert‐butyl‐1,1,3,3‐tetramethylguanidine BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S−O bond linkages in a single step often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click‐principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science.
CCDC 247819: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2005
DOI: 10.5517/CC89W5L
Biomimetic synthesis of (±)-9,10-deoxytridachione
Publisher: Royal Society of Chemistry (RSC)
Date: 2005
DOI: 10.1039/B418988D
Abstract: A tandem Suzuki-coupling/electrocyclisation reaction sequence was employed for the biomimetic synthesis of (+/-)-9,10-deoxytridachione.
Structure-based design of selective high-affinity telomeric quadruplex-binding ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C0CC02917C
Abstract: A library of triazole-based telomeric quadruplex-selective ligands has been developed that mimic an established family of tri-substituted acridine-based ligands, using crystal structure data as a starting-point for computer-based design. Binding affinities, estimated by electrospray mass spectrometry, are in accord with the design concept.
Interactions of marine-derived gamma-pyrone natural products with phospholipid membranes
Publisher: Royal Society of Chemistry (RSC)
Date: 2012
DOI: 10.1039/C2CP42920A
Abstract: The sacoglossan mollusc-derived metabolite, tridachiahydropyrone (3), and its proposed biosynthetic precursors (1 and 2) form part of a complex chemical defence system against predators and harmful UV light. Here, we provide supporting biophysical evidence that the metabolites become selectively localised at cell membranes and outline a binding scheme that accommodates the observed data. The possibility that localised lipid domains within the membrane have an effect on the localisation is also addressed.
Total Synthesis of Polypropionate-Derived gamma-Pyrone Natural Products
Publisher: Georg Thieme Verlag KG
Date: 10-08-2011
The total synthesis of spectinabilin and its biomimetic conversion to SNF4435C and SNF4435D
Publisher: American Chemical Society (ACS)
Date: 12-05-2005
DOI: 10.1021/OL0507874
Abstract: [reaction: see text] A short synthesis of (+/-)-spectinabilin via a trans-selective Suzuki coupling and subsequent Negishi-type methylation, and its biomimetic conversion to (+/-)-SNF4435C and (+/-)-SNF4435D is described.
Formal synthesis of kingianin A based upon a novel electrochemically-induced radical cation Diels-Alder reaction
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4CC05906A
Abstract: The application of electrochemical reactions in natural product synthesis has burgeoned in recent years. We herein report a formal synthesis of the complex and dimeric natural product kingianin A, which employs an electrochemically-mediated radical cation Diels–Alder cycloaddition as the key step.
An efficient entry to 1,2-benzisoxazoles via 1,3-dipolar cycloaddition of in situ generated nitrile oxides and benzyne
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/B927235F
Abstract: An efficient protocol for the synthesis of a range of 1,2-benzisoxazoles using an improved 1,3-dipolar cycloaddition of nitrile oxides and benzyne is described. Key to the procedure is the in situ generation of the reactive nitrile oxide and benzyne reactants simultaneously.
Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
Publisher: American Chemical Society (ACS)
Date: 04-12-2018
DOI: 10.26434/CHEMRXIV.7312595.V3
Abstract: Sulfur-Fluoride Exchange (SuFEx) is the new generation click chemistry transformation exploiting the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient synthesis of pharmaceutically important triflones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF 3 ) upon activation with potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. A tentative catalytic mechanism is proposed supported by DFT calculations, involving formation of the free trifluoromethyl anion followed by nucleophilic displacement of the S-F through a five-coordinate intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late-stage functionalization of bioactive molecules.
Targeting telomerase and telomeres: a click chemistry approach towards highly selective G-quadruplex ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B801822G
Abstract: Maintenance of telomeres--specialized complexes that protect the ends of chromosomes, is undertaken by the enzyme complex telomerase, which is a key factor that is activated in more than 80% of cancer cells, but is absent in most normal cells. Targeting telomere maintenance mechanisms could potentially halt tumour growth across a broad spectrum of cancer types, with little cytotoxic effect outside cancer cells. Here, we describe in detail a new class of G-quadruplex binding ligands synthesized using a click chemistry approach. These ligands comprise a 1,3-di(1,2,3-triazol-4-yl)benzene pharmacophore, and display high levels of selectivity for interaction with G-quadruplex DNA vs. duplex DNA. The ability of these ligands to inhibit the enzymatic activity of telomerase correlates with their ability to stabilize quadruplex DNA, and with estimates of affinity calculated by molecular modeling.
Catalytic Reduction of ortho- and para-Azidonitrobenzenes via tert-Butoxide Ion Mediated Electron Transfer
Publisher: Georg Thieme Verlag KG
Date: 06-02-2013
Modification of Carbon Fibre Surfaces by Sulfur‐Fluoride Exchange Click Chemistry
Publisher: Wiley
Date: 11-10-2018
Abstract: Technologies that enable surface modification are in high demand and are critical for the implementation of new functional materials and devices. Here, we describe the first modification of a carbon surface (in this case carbon fiber) using the sulfur-fluoride exchange (SuFEx) reaction. The parent sulfur (VI) fluoride moiety can be installed directly to the surface via electrochemical deposition of the fluorosulfate phenyldiazonium tetrafluoroborate salt, or by 'SuFExing' a phenol on the carbon surface followed by treatment of the material with SO
Bifluoride Ion Catalyzed Late-Stage SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
Publisher: American Chemical Society (ACS)
Date: 08-11-2018
DOI: 10.26434/CHEMRXIV.7312595.V1
Abstract: Sulfur-Fluoride Exchange (SuFEx) is a new generation click chemistry transformation that exploits the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient late-stage synthesis of pharmaceutically important trifluoromethyl sulfones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF 3 , Ruppert’s reagent), upon activation with catalytic potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. DFT calculations provide the first reported mechanism of anhydrous SuFEx reactivity, which confirms catalytic bifluoride behaviour with a five-coordinate sulfur intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late stage functionalization of bioactive molecules.
Bifluoride Ion Catalyzed Late-Stage SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
Publisher: American Chemical Society (ACS)
Date: 15-11-2018
DOI: 10.26434/CHEMRXIV.7312595.V2
Abstract: Sulfur-Fluoride Exchange (SuFEx) is a new generation click chemistry transformation that exploits the unique properties of S-F bonds and their ability to undergo near-perfect reactions with nucleophiles. We report here the first SuFEx based protocol for the efficient late-stage synthesis of pharmaceutically important trifluoromethyl sulfones and bis(trifluoromethyl)sulfur oxyimines from the corresponding sulfonyl fluorides and iminosulfur oxydifluorides, respectively. The new protocol involves the rapid exchange of the S-F bond with trifluoromethyltrimethylsilane (TMSCF 3 , Ruppert’s reagent), upon activation with catalytic potassium bifluoride in anhydrous DMSO. The reaction tolerates a wide selection of substrates and proceeds under mild conditions without need for chromatographic purification. DFT calculations provide the first reported mechanism of anhydrous SuFEx reactivity, which confirms catalytic bifluoride behaviour with a five-coordinate sulfur intermediate. The preparation of a benzothiazole derived bis(trifluoromethyl)sulfur oxyimine with cytotoxic selectivity for MCF7 breast cancer cells demonstrates the utility of this methodology for the late stage functionalization of bioactive molecules.
Metal‐Free Synthesis of Functional 1‐Substituted‐1,2,3‐Triazoles from Ethenesulfonyl Fluoride and Organic Azides
Publisher: Wiley
Date: 28-11-2020
Abstract: 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 Cu I ‐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.
Inhibition of mitochondrial metabolism by (−)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D3MD00049D
Abstract: We report an improved 4-step semisynthesis of (−)-jerantinine A and (−)-melodinine P from (−)-tabersonine, qualify their potency against TNBC cells and confirm they induce oxidative stress. JA also acts as a potent inhibitor of nucleotide metabolism.
The biomimetic synthesis of SNF4435C and SNF4435D, and the total synthesis of the polyene metabolites aureothin, N-acetyl-aureothamine and spectinabilin
Publisher: Elsevier BV
Date: 02-2006
CCDC 239363: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2006
DOI: 10.5517/CC812DR
CCDC 247818: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2006
DOI: 10.5517/CC89W4K
Horner-Wadsworth-Emmons approach to piperlongumine analogues with potent anti-cancer activity
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6OB01160H
Abstract: Horner–Wadsworth–Emmons approach to a selection of piperlongumine-like compounds from a novel phosphonoacetamide reagent.
Catalyst-Free Regioselective Hydrostannation of Arynes
Publisher: Georg Thieme Verlag KG
Date: 27-09-2011
Mechanism of intersubunit ketosynthase-dehydratase interaction in polyketide synthases
Publisher: Springer Science and Business Media LLC
Date: 08-01-2018
CCDC 200555: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPJ3
Accelerated SuFEx Click Chemistry For Modular Synthesis**
Publisher: Wiley
Date: 07-12-2022
Abstract: SuFEx click chemistry is a powerful method designed for the selective, rapid, and modular synthesis of functional molecules. Classical SuFEx reactions form stable S−O linkages upon exchange of S−F bonds with aryl silyl‐ether substrates, and while near‐perfect in their outcome, are sometimes disadvantaged by relatively high catalyst loadings and prolonged reaction times. We herein report the development of accelerated SuFEx click chemistry (ASCC), an improved SuFEx method for the efficient and catalytic coupling of aryl and alkyl alcohols with a range of SuFExable hubs. We demonstrate Barton's hindered guanidine base (2‐tert‐butyl‐1,1,3,3‐tetramethylguanidine BTMG) as a superb SuFEx catalyst that, when used in synergy with silicon additive hexamethyldisilazane (HMDS), yields stable S−O bond linkages in a single step often within minutes. The powerful combination of BTMG and HMDS reagents allows for catalyst loadings as low as 1.0 mol % and, in congruence with click‐principles, provides a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the number of accessible SuFEx products and will find significant application in organic synthesis, medicinal chemistry, chemical biology, and materials science.
Bifluoride Ion Mediated SuFEx Trifluoromethylation of Sulfonyl Fluorides and Iminosulfur Oxydifluorides
Publisher: Wiley
Date: 27-02-2019
CCDC 209300: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2004
DOI: 10.5517/CC70SMM
Photochemical Studies of the Tridachiahydropyrones in Seawater
Publisher: Georg Thieme Verlag KG
Date: 02-12-2010
Synthesis and biological evaluation of hybrid acridine-HSP90 ligand conjugates as telomerase inhibitors
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5OB01177A
Abstract: The synthesis and biological evaluation of a series of bifunctional acridine-HSP90 inhibitor ligands as telomerase inhibitors is herein described.
Structural characterisation of the NADH binary complex of human lactate dehydrogenase M isozyme
Publisher: Worldwide Protein Data Bank
Date: 30-04-2014
DOI: 10.2210/PDB4L4S/PDB
Ethynyldiisopropylsilyl: A New Allrynylsilane Protecting Group and Click Linker
Publisher: American Chemical Society (ACS)
Date: 20-05-2010
DOI: 10.1021/OL100968T
Abstract: A new silyl-based reagent has been developed for "catch and release" immobilization, combining click chemistry with silyl protection. The traditional "all carbon" attachment to solid supports in a silyl type linker was substituted with a stable triazole, easily assembled using the CuAAC reaction. The methodology introduces a novel ethynyldiiospropylchlorosilane reagent (EDIPS-Cl) as a functionalized protecting group linker.
Thermally induced cascade pericyclic reaction pathways from tetraene esters
Publisher: Elsevier BV
Date: 08-2003
Synthesis of 1,2,4-Triazol-3-imines via Selective Stepwise Cycloaddition of Nitrile Imines with Organo-cyanamides
Publisher: American Chemical Society (ACS)
Date: 28-06-2018
DOI: 10.1021/ACS.ORGLETT.8B01673
Abstract: A convenient method for the synthesis of 1,2,4-triazol-3-imines through a selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by DFT calculations, is invoked to explain the reaction selectivity.
Frontispiece: Sulfur-Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates
Publisher: Wiley
Date: 26-07-2017
Sustainable Syntheses of (−)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site
Publisher: Springer Science and Business Media LLC
Date: 13-07-2018
DOI: 10.1038/S41598-018-28880-2
Abstract: The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (−)-jerantinines A and E from sustainably sourced (−)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (−)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin—(−)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.
CCDC 200556: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPK4
CCDC 209361: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2004
DOI: 10.5517/CC70VLN
Biomimetic studies on polyenes
Publisher: Royal Society of Chemistry (RSC)
Date: 2003
DOI: 10.1039/B306933H
Abstract: The crispatenes and SNF4435 C&D are complex polypropionate derived natural products. The core structures of these compounds along with a complex unnatural structure can be easily prepared from a common polyene precursor simply by variation of the reaction conditions. The reaction pathways provide insight into the biosynthesis of these complex natural products.
CCDC 239364: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2005
DOI: 10.5517/CC812FS
Biomimetic Synthesis of Pyrone-Derived Natural Products: Exploring Chemical Pathways from a Unique Polyketide Precursor
Publisher: American Chemical Society (ACS)
Date: 03-06-2008
DOI: 10.1021/JO800220W
Abstract: Our biomimetic hypothesis proposes that families of erse natural products with complex core structures such as 9,10-deoxytridachione, photodeoxytridachione and ocellapyrone A are derived in nature from a linear and conformationally strained all-( E) tetraene-pyrone precursor. We therefore synthesized such a precursor and investigated its biomimetic transformation under a variety of reaction conditions, both to the above natural products as well as to erse isomers which we propose to be natural products "yet to be discovered". We also report herein the first synthesis of the natural product iso-9,10-deoxytridachione.
Carbene Footprinting Reveals Binding Interfaces of a Multimeric Membrane‐Spanning Protein
Publisher: Wiley
Date: 20-10-2017
Abstract: Mapping the interaction sites between membrane-spanning proteins is a key challenge in structural biology. In this study a carbene-footprinting approach was developed and applied to identify the interfacial sites of a trimeric, integral membrane protein, OmpF, solubilised in micelles. The diazirine-based footprinting probe is effectively sequestered by, and incorporated into, the micelles, thus leading to efficient labelling of the membrane-spanning regions of the protein upon irradiation at 349 nm. Areas associated with protein-protein interactions between the trimer subunits remained unlabelled, thus revealing their location.
CCDC 247820: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2005
DOI: 10.5517/CC89W6M
New Biological Activities of Casimiroa edulis Leaf Extract and Isolated Compounds
Publisher: Wiley
Date: 15-12-2011
DOI: 10.1002/PTR.3690
Abstract: The phytochemical investigation of Casimiroa edulis Llave et Lex (Rotaceae) afforded four coumarins: umbelliferone (1), esculetin (2), imperatorin (3) and xanthotoxol (4). The identification of these compounds was achieved by using a combination of m.p., UV, EI-mass, ¹H NMR and ¹³C NMR spectroscopy. Essential oil extracts were analysed by GC/MS leading to the identification of 60 components. Sesquiterpene hydrocarbons accounted for the major make up of the oil. Microbiological screenings of the oil and successive plant fractions were performed, showing promising activity against a number of microorganisms with Minimum inhibitory concentrations (MIC) comparable to the standard antibiotics such as chlor henicol and kanamycin. The plant ethanol extract (400 mg/kg) and the isolated coumarins (60 mg/kg) showed anticoagulant activity. Analyses to determine the activity of the extracts on liver and kidney function were performed, revealing no negative or detrimental effects.
Carbene footprinting accurately maps binding sites in protein–ligand and protein–protein interactions
Publisher: Springer Science and Business Media LLC
Date: 16-11-2016
DOI: 10.1038/NCOMMS13288
Abstract: Specific interactions between proteins and their binding partners are fundamental to life processes. The ability to detect protein complexes, and map their sites of binding, is crucial to understanding basic biology at the molecular level. Methods that employ sensitive analytical techniques such as mass spectrometry have the potential to provide valuable insights with very little material and on short time scales. Here we present a differential protein footprinting technique employing an efficient photo-activated probe for use with mass spectrometry. Using this methodology the location of a carbohydrate substrate was accurately mapped to the binding cleft of lysozyme, and in a more complex ex le, the interactions between a 100 kDa, multi-domain deubiquitinating enzyme, USP5 and a diubiquitin substrate were located to different functional domains. The much improved properties of this probe make carbene footprinting a viable method for rapid and accurate identification of protein binding sites utilizing benign, near-UV photoactivation.
Targeting glycolysis: a fragment based approach towards bifunctional inhibitors of hLDH-5
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0CC01166E
Abstract: hLDH-5 has emerged as a promising target for anti-glycolytic cancer chemotherapy. Here we report a first generation of bifunctional inhibitors, which show promising activity against hLDH-5.
Total synthesis of cyercene A and the biomimetic synthesis of (±)-9,10-deoxytridachione and (±)-ocellapyrone A
Publisher: Elsevier BV
Date: 05-2007
Synthesis of Oxadiazol-5-imines via the Cyclizative Capture of in Situ Generated Cyanamide Ions and Nitrile Oxides.
Publisher: American Chemical Society (ACS)
Date: 18-02-2016
DOI: 10.1021/ACS.ORGLETT.6B00203
Abstract: An unprecedented intermolecular cyclizative capture of the cyanamide anion and several nitrile oxides enables the synthesis of oxadiazol-5-imines.
Frontispiz: Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs
Publisher: Wiley
Date: 13-07-2021
Sulfur fluoride exchange
Publisher: Springer Science and Business Media LLC
Date: 03-08-2023
New tantalum compounds supported by 3,3 '-disubstituted-1,1 '-bi-2-naphthoxide ligation
Publisher: Royal Society of Chemistry (RSC)
Date: 2000
DOI: 10.1039/B005681M
Ethene‐1,1‐disulfonyl Difluoride (EDSF) for SuFEx Click Chemistry: Synthesis of SuFExable 1,1‐Bissulfonylfluoride Substituted Cyclobutene Hubs
Publisher: Wiley
Date: 15-06-2023
Abstract: We present the synthesis of 1,1‐bis(fluorosulfonyl)‐2‐(pyridin‐1‐ium‐1‐yl)ethan‐1‐ide, a bench‐stable precursor to ethene‐1,1‐disulfonyl difluoride (EDSF). The novel SuFEx reagent, EDSF, is demonstrated in the preparation of 26 unique 1,1‐bissulfonylfluoride substituted cyclobutenes via a cycloaddition reaction. The regioselective click cycloaddition reaction is rapid, straightforward, and highly efficient, enabling the generation of highly functionalized 4‐membered ring (4MR) carbocycles. These carbocycles are valuable structural motifs found in numerous bioactive natural products and pharmaceutically relevant small molecules. Additionally, we showcase ersification of the novel cyclobutene cores through selective Cs 2 CO 3 ‐activated SuFEx click chemistry between a single S−F group and an aryl alcohol, yielding the corresponding sulfonate ester products with high efficiency. Finally, density functional theory calculations offer mechanistic insights about the reaction pathway.
Benzyne Click Chemistry with in Situ Generated Aromatic Azides
Publisher: American Chemical Society (ACS)
Date: 06-03-2009
DOI: 10.1021/OL9002338
Abstract: An efficient synthesis of substituted benzotriazoles using an azide-alkyne 1,3-dipolar cycloaddition "click reaction" is described. Key to the procedure is the in situ generation of the reactive aromatic azide and benzyne reaction partners.
Structural characterization of the apo form and NADH binary complex of human lactate dehydrogenase
Publisher: International Union of Crystallography (IUCr)
Date: 30-04-2014
DOI: 10.1107/S1399004714005422
Abstract: Lactate dehydrogenase A (LDH-A) is a key enzyme in anaerobic respiration that is predominantly found in skeletal muscle and catalyses the reversible conversion of pyruvate to lactate in the presence of NADH. LDH-A is overexpressed in many tumours and has therefore emerged as an attractive target for anticancer drug discovery. Crystal structures of human LDH-A in the presence of inhibitors have been described, but currently no structures of the apo or binary NADH-bound forms are available for any mammalian LDH-A. Here, the apo structure of human LDH-A was solved at a resolution of 2.1 Å in space group P 4 1 22. The active-site loop adopts an open conformation and the packing and crystallization conditions suggest that the crystal form is suitable for soaking experiments. The soaking potential was assessed with the cofactor NADH, which yielded a ligand-bound crystal structure in the absence of any inhibitors. The structures show that NADH binding induces small conformational changes in the active-site loop and an adjacent helix. A comparison with other eukaryotic apo LDH structures reveals the conservation of intra-loop interactions. The structures provide novel insight into cofactor binding and provide the foundation for soaking experiments with fragments and inhibitors.
New Synthesis of 1-Substituted-1H-indazoles via 1,3-Dipolar Cycloaddition of in situ Generated Nitrile Imines and Benzyne
Publisher: American Chemical Society (ACS)
Date: 07-07-2010
DOI: 10.1021/OL101150T
Abstract: A new synthesis of 1-substituted-1H-indazoles via 1,3-dipolar cycloaddition of nitrile imines to benzyne is described. The reaction is completed within 5 min, affording the corresponding N(1)-C(3) disubstituted indazoles in moderate to excellent yields.
A catalytic and tert-butoxide ion-mediated amidation of aldehydes with para-nitro azides
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C3CC40452H
Abstract: We report here a new catalytic reaction in which, para-nitro azides are acylated by aldehydes to produce amides and molecular nitrogen in a single step. The transformation is believed to proceed via an electron transfer process mediated by the tert-butoxide ion, and catalysed by a thiazolium salt derived species.
A click chemistry approach to C3 symmetric, G-quadruplex stabilising ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2010
DOI: 10.1039/C005055E
Abstract: Described is the structure-based design and synthesis of a series of tris-triazole G-quadruplex binding ligands utilising the copper catalysed azide-alkyne 'click' reaction. The results of G-quadruplex stabilisation by the ligands are reported and discussed.
CCDC 200557: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPL5
The growing applications of click chemistry
Publisher: Royal Society of Chemistry (RSC)
Date: 2007
DOI: 10.1039/B613014N
Abstract: Click chemistry, the subject of this tutorial review, is a modular synthetic approach towards the assembly of new molecular entities. This powerful strategy relies mainly upon the construction of carbon-heteroatom bonds using spring-loaded reactants. Its growing number of applications are found in nearly all areas of modern chemistry from drug discovery to materials science. The copper(I)-catalysed 1,2,3-triazole forming reaction between azides and terminal alkynes has become the gold standard of click chemistry due to its reliability, specificity and biocompatibility.
Copper-Catalyzed Azide-Alkyne Cycloaddition: Regioselective Synthesis of 1,4,5-Trisubstituted 1,2,3-Triazoles
Publisher: Wiley
Date: 22-12-2015
CCDC 190072: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6CSCP
Chemoselective Synthesis of Polysubstituted Pyridines from Heteroaryl Fluorosulfates
Publisher: Wiley
Date: 15-03-2016
Selectivity of small molecule ligands for parallel and anti-parallel DNA G-quadruplex structures
Publisher: Royal Society of Chemistry (RSC)
Date: 2009
DOI: 10.1039/B910505K
Abstract: We report CD, ESI-MS and molecular modelling studies of ligand binding interactions with DNA quadruplex structures derived from the human telomeric repeat sequence (h-Tel) and the proto-oncogenic c-kit promoter sequence. These sequences form anti-parallel (both 2 + 2 and 3 + 1) and parallel conformations, respectively, and demonstrate distinctively different degrees of structural plasticity in binding ligands. With h-Tel, we show that an extended heteroaromatic 1,4-triazole (TRZ), designed to exploit pi-stacking interactions and groove-specific contacts, shows some selectivity for parallel folds, however, the polycyclic fluorinated acridinium cation (RHPS4), which is a similarly potent telomerase inhibitor, shows selectivity for anti-parallel conformations implicating favourable interactions with lateral and diagonal loops. In contrast, the unique c-kit parallel-stranded quadruplex shows none of the structural plasticity of h-Tel with either ligand. We show by quantitative ESI-MS analysis that both sequences are able to bind a ligand on either end of the quadruplex. In the case of h-Tel the two sites have similar affinities, however, in the case of the c-kit quadruplex the affinities of the two sites are different and ligand-dependent. We demonstrate that two different small molecule architectures result in significant differences in selectivity for parallel and anti-parallel quadruplex structures that may guide quadruplex targeted drug-design.
Reengineering Antibiotics to Combat Bacterial Resistance: Click Chemistry [1,2,3]‐Triazole Vancomycin Dimers with Potent Activity against MRSA and VRE
Publisher: Wiley
Date: 11-11-2017
Abstract: Vancomycin has long been considered a drug of last resort. Its efficiency in treating multiple drug-resistant bacterial infections, particularly methicillin-resistant Staphylococcus aureus (MRSA), has had a profound effect on the treatment of life-threatening infections. However, the emergence of resistance to vancomycin is a cause for significant worldwide concern, prompting the urgent development of new effective treatments for antibiotic resistant bacterial infections. Harnessing the benefits of multivalency and cooperativity against vancomycin-resistant strains, we report a Click Chemistry approach towards reengineered vancomycin derivatives and the synthesis of a number of dimers with increased potency against MRSA and vancomycin resistant Enterococci (VRE VanB). These semi-synthetic dimeric ligands were linked together with great efficiency using the powerful CuAAC reaction, demonstrating high levels of selectivity and purity.
A novel click-chemistry approach to flame retardant polyurethanes
Publisher: Elsevier BV
Date: 09-2013
A Silver-Mediated One-Step Synthesis of Oxazoles
Publisher: American Chemical Society (ACS)
Date: 06-04-2011
DOI: 10.1021/JO1025332
Abstract: A silver-mediated one-step procedure to 2,4-disubstituted and 2,4,5-trisubstituted oxazoles has been developed. The method is complementary to existing technologies, yet provides advantages with regard to simplicity, efficiency, and performance. The silver product can be readily recycled, thus minimizing waste.
CCDC 705489: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2010
DOI: 10.5517/CCRP3Q7
Biomimetic Synthesis and Structural Reassignment of the Tridachiahydropyrones
Publisher: American Chemical Society (ACS)
Date: 02-04-2009
DOI: 10.1021/JA900369Z
Abstract: The biomimetic synthesis and structural reassignment of tridachiahydropyrone, tridachiahydropyrone B and tridachiahydropyrone C, isolated from mollusks of the order Sacoglossa, using a sequence of photochemical transformations from a common polyene precursor are described. These complex natural products may act as sunscreens for the producing organism, thus offering protection from harmful UV radiation and oxidative damage.
Biomimetic Approaches Towards the Synthesis of Complex Dimeric Natural Products
Publisher: Bentham Science Publishers Ltd.
Date: 29-03-2016
DOI: 10.2174/1381612822666160101123106
Abstract: We present a selection of elegant and erse biomimetic syntheses of complex natural product dimers. The dimerisation pathways discussed encompass the most prevalent strategies, including: Diels-Alder, Aldol, Mannich, conjugate addition, oxidative, radical and photochemical approaches each underpinned through rational biosynthetic speculation.
The certainty of a few good reactions
Publisher: Elsevier BV
Date: 08-2023
1-Bromoethene-1-sulfonyl fluoride (BESF) is another good connective hub for SuFEx click chemistry
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CC03400A
Abstract: 1,2-Dibromoethane-1-sulfonyl fluoride ( DESF ): a bench stable and readily accessible precursor to BESF for the synthesis of β-sultams, sulfonyl fluoride substituted isoxazoles, triazoles and Michael adducts with SuFEx-able pendant sulfonyl fluoride handles.
Microwave enhancement of a 'one-pot' tandem azidation-'click' cycloaddition of anilines
Publisher: Georg Thieme Verlag KG
Date: 08-2008
Ligand selectivity in stabilising tandem parallel folded G-quadruplex motifs in human telomeric DNA sequences
Publisher: Royal Society of Chemistry (RSC)
Date: 23-10-2014
DOI: 10.1039/C4CC07487D
Abstract: Biophysical studies of ligand interactions with three human telomeric repeat sequences (d(AGGG(TTAGGG)n, n = 3, 7 and 11)) show that an oxazole-based 'click' ligand, which induces parallel folded quadruplexes, preferentially stabilises longer telomeric repeats providing evidence for selectivity in binding at the interface between tandem quadruplex motifs.
Sir Jack Baldwin, FRS: Biomimetic studies at Oxford
Publisher: Royal Society of Chemistry (RSC)
Date: 2005
DOI: 10.1039/B512961C
CCDC 200558: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2003
DOI: 10.5517/CC6QPM6
Ethene‐1,1‐disulfonyl Difluoride (EDSF) for SuFEx Click Chemistry: Synthesis of SuFExable 1,1‐Bissulfonylfluoride Substituted Cyclobutene Hubs
Publisher: Wiley
Date: 15-06-2023
Abstract: We present the synthesis of 1,1‐bis(fluorosulfonyl)‐2‐(pyridin‐1‐ium‐1‐yl)ethan‐1‐ide, a bench‐stable precursor to ethene‐1,1‐disulfonyl difluoride (EDSF). The novel SuFEx reagent, EDSF, is demonstrated in the preparation of 26 unique 1,1‐bissulfonylfluoride substituted cyclobutenes via a cycloaddition reaction. The regioselective click cycloaddition reaction is rapid, straightforward, and highly efficient, enabling the generation of highly functionalized 4‐membered ring (4MR) carbocycles. These carbocycles are valuable structural motifs found in numerous bioactive natural products and pharmaceutically relevant small molecules. Additionally, we showcase ersification of the novel cyclobutene cores through selective Cs 2 CO 3 ‐activated SuFEx click chemistry between a single S−F group and an aryl alcohol, yielding the corresponding sulfonate ester products with high efficiency. Finally, density functional theory calculations offer mechanistic insights about the reaction pathway.
Quantitative and Orthogonal Formation and Reactivity of SuFEx Platforms
Publisher: Wiley
Date: 27-06-2018
A New and Efficient Method for o-Quinone Methide Intermediate Generation: Application to the Biomimetic Synthesis of (±)-Alboatrin
Publisher: American Chemical Society (ACS)
Date: 26-08-2004
DOI: 10.1021/OL048479D
Abstract: [reaction: see text] A new and efficient method for o-quinone methide intermediate generation from o-methyleneacetoxy-phenols has been developed and applied to the biomimetic synthesis of (+/-)-Alboatrin.
Biomimetic Synthesis of the Crispatene Core
Publisher: American Chemical Society (ACS)
Date: 08-02-2003
DOI: 10.1021/OL020242Z
Abstract: The biomimetic synthesis of the crispatene core is reported. The core framework was efficiently generated from an easily synthesized all (E)-tetraene precursor in one step, in good yield.
CCDC 237660: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2005
DOI: 10.5517/CC7Z9GY
CCDC 190073: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2004
DOI: 10.5517/CC6CSDQ
Total synthesis of panepophenanthrin
Publisher: American Chemical Society (ACS)
Date: 22-07-2003
DOI: 10.1021/OL0349817
Abstract: [reaction: see text] The biomimetic synthesis of the racemic dimer panepophenanthrin was achieved in good yield employing a tandem reaction sequence.
Click chemistry and medicinal chemistry: A case of "Cyclo-Addiction"
Publisher: Wiley
Date: 08-05-2008
SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase
Publisher: Proceedings of the National Academy of Sciences
Date: 04-09-2019
Abstract: 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 IC 50 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.
CCDC 619001: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2009
DOI: 10.5517/CCNS3S9
CCDC 705490: Experimental Crystal Structure Determination
Publisher: No publisher found
Date: 2010
DOI: 10.5517/CCRP3R8
Phosphorus fluoride exchange: Multidimensional catalytic click chemistry from phosphorus connective hubs
Publisher: Elsevier BV
Date: 08-2023
Studies on the Biomimetic Synthesis of SNF4435 C and D
Publisher: American Chemical Society (ACS)
Date: 27-09-2002
DOI: 10.1021/OL020157R
Abstract: [reaction: see text] The biomimetic synthesis of the bicyclic core of the novel immunosuppresants SNF4435C and SNF4435D is reported. The core framework was efficiently generated from the all-trans tetraene precursor in one step and in good yield.
Accelerated SuFEx Click Chemistry for Modular Synthesis
Publisher: American Chemical Society (ACS)
Date: 25-01-2021
DOI: 10.26434/CHEMRXIV.13623179.V1
Abstract: Click chemistry is a method for the rapid synthesis of functional molecules with desirable properties. We report the development of accelerated SuFEx, a powerful click reaction for the efficient coupling of aryl and alkyl alcohols directly with SuFExable hubs catalyzed by 2- tert -butyl-1,1,3,3-tetramethylguanidine (BTMG, Barton's base). The new method circumvents the need to synthesize silyl ether substrates while allowing the use of sub-stoichiometric catalyst loadings. This is made possible through a synergistic effect between BTMG and hexamethyldisilazane (HMDS) additive. The powerful combination drives the in situ formation of reactive TMS-ether intermediates while exploiting the silicon-fluoride bond formation's thermodynamic driving force. Comparatively, the required BTMG base's catalyst loading is generally low (1.0–20 mol%) compared to the dominant SuFEx catalyst, DBU (10–30 mol%). In line with click chemistry principles, the scalable reaction only requires simple evaporation of the volatile side products (NH 3 , Me 3 Si-F, TMS-OH, BTMG) under reduced pressure instead of extensive purification. The new SuFEx protocol is tolerant of a wide selection of functional groups and meets all the demands of a click reaction, thereby dramatically shortening reaction times and delivering products in excellent yield.
A new and efficient method for o-quinone methide intermediate generation: application to the biomimetic synthesis of the benzopyran derived natural products (±)-lucidene and (±)-alboatrin
Publisher: Royal Society of Chemistry (RSC)
Date: 2005
DOI: 10.1039/B508972G
Abstract: Lucidene and alboatrin are complex benzopyran derived natural products. A key step in their biogenesis may involve a hetero Diels-Alder cycloaddition between an o-quinone methide intermediate with a simple, or activated tri-substituted olefin. Experimental evidence is provided to support this hypothesis, with the biomimetic synthesis of both (+/-)-lucidene and (+/-)-alboatrin successfully achieved using a new and efficient method for o-quinone methide generation.
Silver mediated one-step synthesis of oxazoles from α-haloketones
Publisher: Elsevier BV
Date: 10-2011
Related Organisations
University Of Oxford Department Of Chemistry
Location: United Kingdom of Great Britain and Northern Ireland
University Of Nottingham
Location: United Kingdom of Great Britain and Northern Ireland
School Of Pharmacy, University Of London (now UCL)
Location: United Kingdom of Great Britain and Northern Ireland
University Of Bath
Location: United Kingdom of Great Britain and Northern Ireland
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ARC Future Fellowships - Grant ID: FT170100156
Start Date: 07-2017
End Date: 08-2020
Amount: $940,000.00
Funder: Australian Research Council
View Funded ActivityIndustrial Transformation Research Hubs - Grant ID: IH180100006
Start Date: 07-2019
End Date: 07-2024
Amount: $4,995,391.00
Funder: Australian Research Council
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