- Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination
-
Abundant aromatic carboxylic acids exist in great structural diversity from nature and synthesis. To date, the synthetically valuable decarboxylative functionalization of benzoic acids is realized mainly by transition-metal-catalyzed decarboxylative cross couplings. However, the high activation barrier for thermal decarboxylative carbometalation that often requires 140 °C reaction temperature limits both the substrate scope as well as the scope of suitable reactions that can sustain such conditions. Numerous reactions, for example, decarboxylative fluorination that is well developed for aliphatic carboxylic acids, are out of reach for the aromatic counterparts with current reaction chemistry. Here, we report a conceptually different approach through a low-barrier photoinduced ligand to metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation strategy, which generates a putative high-valent arylcopper(III) complex, from which versatile facile reductive eliminations can occur. We demonstrate the suitability of our new approach to address previously unrealized general decarboxylative fluorination of benzoic acids.
- Xu, Peng,López-Rojas, Priscila,Ritter, Tobias
-
supporting information
p. 5349 - 5354
(2021/05/05)
-
- Formation of 1-hydroxymethylene-1,1-bisphosphinates through the addition of a silylated phosphonite on various trivalent derivatives
-
An easily handled one-pot synthetic procedure was previously developed for the synthesis of bisphosphinates starting from acyl chlorides. Herein, other trivalent derivatives as acid anhydrides and activated esters were tested to form various bisphosphinates. This modulation of the reactivity can be controlled according to the nature of the acid derivative for the use of sensitive and functionalized substrates.
- Dussart-Gautheret, Jade,Deschamp, Julia,Monteil, Maelle,Gager, Olivier,Legigan, Thibaut,Migianu-Griffoni, Evelyne,Lecouvey, Marc
-
p. 14559 - 14569
(2020/12/29)
-
- Small molecular PET photographic developer of target chemokine receptor CXCR4
-
The invention relates to a small molecular PET photographic developer of a target chemokine receptor CXCR4 and a preparation method of the small molecular PET photographic developer. According to thesmall molecular PET photographic developer of the target
- -
-
Paragraph 0081-0084
(2020/01/08)
-
- N-Doped Yellow TiO2 Hollow Sphere-Mediated Visible-Light-Driven Efficient Esterification of Alcohol and N-Hydroxyimides to Active Esters
-
Herein we report a simple synthetic protocol for N-doped yellow TiO2 (N-TiO2) hollow spheres as an efficient visible-light-active photocatalyst using aqueous titanium peroxocarbonate complex (TPCC) solution as precursor and NH4OH. In the developed strategy, the ammonium ion of TPCC and NH4OH acts as nitrogen source and structure-directing agent. The synthesized N-TiO2 hollow spheres are capable of promoting the synthesis of active esters of N-hydroxyimide and alcohol through simultaneous selective oxidation of alcohol to aldehyde followed by cross-dehydrogenative coupling (CDC) under ambient conditions upon irradiation of visible light. It is possible to develop a novel and cost-effective one-pot strategy for the synthesis of important esters and amides on gram scale using the developed strategy. The catalytic activity of N-TiO2 hollow spheres is much superior to that of other reported N-TiO2 samples as well as TiO2 with varying morphology.
- Singha, Krishnadipti,Ghosh, Subhash Ch.,Panda, Asit Baran
-
p. 3205 - 3212
(2019/09/09)
-
- RADIOACTIVE COMPOUND FOR DIAGNOSIS OF MALIGNANT MELANOMA AND USE THEREOF
-
The present invention provides a novel radioactive compound for imaging malignant melanoma and a use thereof as a contrast agent for PET imaging.
- -
-
Paragraph 00054-0057
(2019/11/19)
-
- MYELOPEROXIDASE IMAGING AGENTS
-
Provided herein are compounds useful as imaging agents. Exemplary compounds provided herein are useful as myeloperoxidase imaging agents using positron emission tomography or fluorescence imaging techniques. Methods for preparing the compounds provided herein and diagnostic methods using radiolabeled and unlabeled compounds are also provided.
- -
-
Page/Page column 50; 81
(2018/06/06)
-
- Atmospheric oxidative catalyst-free cross-dehydrogenative coupling of aldehydes with N-hydroxyimides
-
Cross-dehydrogenative coupling (CDC) reactions of aldehydes with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI) under catalyst-free conditions is described. Moreover, the desired products can be obtained simply by recrystallization from ethanol. This method is also applicable to the synthesis of amides in excellent yields. A radical mechanism of the type shown in Scheme 4 is proposed based upon the inhibition of the reaction in the presence of TEMPO.
- Xu, Xiaohe,Li, Pingping,Huang, Yingyi,Tong, Chuo,Yan, YiYan,Xie, Yuanyuan
-
supporting information
p. 1742 - 1746
(2017/04/13)
-
- Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands
-
Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.
- Taylor, Nicholas J.,Emer, Enrico,Preshlock, Sean,Schedler, Michael,Tredwell, Matthew,Verhoog, Stefan,Mercier, Joel,Genicot, Christophe,Gouverneur, Véronique
-
supporting information
p. 8267 - 8276
(2017/06/27)
-
- Iron-Nitrate-Catalyzed Oxidative Esterification of Aldehydes and Alcohols with N-Hydroxyphthalimide: Efficient Synthesis of N-Hydroxyimide Esters
-
An Fe(NO3)3·9H2O-catalyzed cross-dehydrogenative coupling reaction between N-hydroxyphthalimide (NHPI) or N-hydroxysuccinimide (NHSI) and aldehydes or alcohols in air is described. This transformation represents an efficient approach to the preparation of N-hydroxyimide ester derivatives in moderate to excellent yields, and has a wide substrate scope.
- Xu, Xiaohe,Sun, Jian,Lin, Yuyan,Cheng, Jingya,Li, Pingping,Jiang, Xiaoying,Bai, Renren,Xie, Yuanyuan
-
supporting information
p. 7160 - 7166
(2017/12/28)
-
- Prototypic 18F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma
-
The neuropeptide Y (NPY) Y1 receptor (Y1R) selective radioligand (R)-Nα-(2,2-diphenylacetyl)-Nω-[4-(2-[18F]fluoropropanoylamino)butyl]aminocarbonyl-N-(4-hydroxybenzyl)argininamide ([18F]23), derived from the high-affinity Y1R antagonist BIBP3226, was developed for imaging studies of Y1R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y1R affinity. The fluoropropanoylated derivative 23 displayed high affinity (Ki = 1.3 nM) and selectivity toward Y1R. Radiosynthesis was accomplished via 18F-fluoropropanoylation, yielding [18F]23 with excellent stability in mice; however, the biodistribution study revealed pronounced hepatobiliary clearance with high accumulation in the gall bladder (>100 %ID/g). Despite the unfavorable biodistribution, [18F]23 was successfully used for imaging of Y1R positive MCF-7 tumors in nude mice. Therefore, we suggest [18F]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y1R-dependent enrichment in mammary carcinoma.
- Keller, Max,Maschauer, Simone,Brennauer, Albert,Tripal, Philipp,Koglin, Norman,Dittrich, Ralf,Bernhardt, Günther,Kuwert, Torsten,Wester, Hans-Jürgen,Buschauer, Armin,Prante, Olaf
-
supporting information
p. 304 - 309
(2017/03/17)
-
- A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [18F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging
-
Background Numerous clinical studies have shown a correlation between increased matrix metalloproteinase (MMP)/a disintegrin and metalloproteinase (ADAM) activity and poor outcome of cancer. Various MMP inhibitors (MMPIs) have been developed for therapeutic purposes in oncology. In addition, molecular imaging of MMP/ADAM levels in vivo would allow the diagnosis of tumors. We selected the dual inhibitor of MMPs and ADAMs, ML5, which is a hydroxamate-based inhibitor with affinities for many MMPs and ADAMs. ML5 was radiolabelled with 18F and the newly obtained radiolabelled inhibitor was evaluated in vitro and in vivo. Materials and methods ML5 was radiolabelled by direct acylation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) for PET (positron emission tomography). The resulting radiotracer [18F]FB-ML5 was evaluated in vitro in human bronchial epithelium 16HBE cells and breast cancer MCF-7 cells. The non-radioactive probe FB-ML5 and native ML5 were tested in a fluorogenic inhibition assay against MMP-2, -9, -12 and ADAM-17. The in vivo kinetics of [18F]FB-ML5 were examined in a HT1080 tumor-bearing mouse model. Specificity of probe binding was examined by co-injection of 0 or 2.5 mg/kg ML5. Results ML5 and FB-ML5 showed high affinity for MMP-2, -9, -12 and ADAM-17; indeed IC50 values were respectively 7.4 ± 2.0, 19.5 ± 2.8, 2.0 ± 0.2 and 5.7 ± 2.2 nM and 12.5 ± 3.1, 31.5 ± 13.7, 138.0 ± 10.9 and 24.7 ± 2.8 nM. Radiochemical yield of HPLC-purified [18F]FB-ML5 was 13-16% (corrected for decay). Cellular binding of [18F]FB-ML5 was reduced by 36.6% and 27.5% in MCF-7 and 16HBE cells, respectively, after co-incubation with 10 μM of ML5. In microPET scans, HT1080 tumors exhibited a low and homogeneous uptake of the tracer. Tumors of mice injected with [18F]FB-ML5 showed a SUVmean of 0.145 ± 0.064 (n = 6) which decreased to 0.041 ± 0.027 (n = 6) after target blocking (p 18F. [18F]FB-ML5 demonstrated rather low binding in ADAM-17 overexpressing cell lines. [18F]FB-ML5 uptake showed significant reduction in the HT1080 tumor in vivo after co-injection of ML5. [18F]FB-ML5 may be suitable for the visualization/quantification of diseases overexpressing simultaneously MMPs and ADAMs.
- Matusiak, Nathalie,Castelli, Riccardo,Tuin, Adriaan W.,Overkleeft, Herman S.,Wisastra, Rosalina,Dekker, Frank J.,Prély, Laurette M.,Bischoff, Rainer P.M.,Van Waarde, Aren,Dierckx, Rudi A.J.O.,Elsinga, Philip H.
-
p. 192 - 202
(2015/02/19)
-
- Palladium-Catalyzed Carbonylation of (Hetero)Aryl, Alkenyl and Allyl Halides by Means of N-Hydroxysuccinimidyl Formate as CO Surrogate
-
An efficient Pd-catalyzed carbonylation protocol is described for the coupling of a large panel of aryl, heteroaryl, benzyl, vinyl and allyl halides 2 with the unusual N-hydroxysuccinimidyl (NHS) formate 1 as a CO surrogate to afford the corresponding valuable NHS esters 3. High conversion to the coupling products was achieved with up to 98% yield by means of Pd(OAc)2/Xantphos catalyst system.
- Barré, Ana?s,T?nta?, Mihaela-Liliana,Alix, Florent,Gembus, Vincent,Papamica?l, Cyril,Levacher, Vincent
-
p. 6537 - 6544
(2015/10/05)
-
- Cross dehydrogenative coupling (CDC) of aldehydes with N-hydroxyimides by visible light photoredox catalysis
-
A photoinduced cross-dehydrogenative-coupling (CDC) reaction between aldehydes and N-hydroxyimides has been developed for the synthesis of ester derivatives. Using 2 mol% [Ru(bpy)3]Cl2 in dry acetonitrile at room temperature with an LED light bulb, we were able to synthesize N-hydroxyesters in good yields. The ester derivatives are very useful synthetic intermediates, which were transformed to amide and oxazole building blocks in excellent yields. This journal is
- Dinda, Milan,Bose, Chandan,Ghosh, Tridev,Maity, Soumitra
-
p. 44928 - 44932
(2015/06/02)
-
- General method for the preparation of active esters by palladium-catalyzed alkoxycarbonylation of aryl bromides
-
A useful method was developed for the synthesis of active esters by palladium-catalyzed alkoxycarbonylation of (hetero)aromatic bromides. The protocol was general for a range of oxygen nucleophiles including N-hydroxysuccinimide (NHS), pentafluorophenol (PFP), hexafluoroisopropyl alcohol (HFP), 4-nitrophenol, and N-hydroxyphthalimide. A high functional group tolerance was displayed, and several active esters were prepared with good to excellent isolated yields. The protocol was extended to access an important synthetic precursor to the HIV-protease inhibitor, saquinavir, by formation of an NHS ester followed by acyl substitution.
- De Almeida, Angelina M.,Andersen, Thomas L.,Lindhardt, Anders T.,De Almeida, Mauro V.,Skrydstrup, Troels
-
supporting information
p. 1920 - 1928
(2015/02/19)
-
- Iodide-catalyzed amide synthesis from alcohols and amines
-
An efficient method to prepare amides by a cascade strategy was developed. Using nBu4NI or NaI as the catalyst and tert-butyl hydroperoxide as the oxidant, various alcohols reacted with N-hydroxysuccinimide or N-hydroxyphthalimide affording corresponding active esters in moderate to good yield. The resulting active esters were converted into amides smoothly in one pot. The Royal Society of Chemistry 2013.
- Wang, Gao,Yu, Qing-Ying,Wang, Jian,Wang, Shan,Chen, Shan-Yong,Yu, Xiao-Qi
-
p. 21306 - 21310
(2013/11/06)
-
- Detecting a peroxide-based explosive via molecular gelation
-
A convenient and portable triacetone triperoxide (TATP) sensor was developed utilizing a thiol-to-disulfide oxidation to trigger a solution-to-gel phase transition. Using this method, TATP can be detected visually without any instrumentation.
- Chen, Jing,Wu, Weiwei,McNeil, Anne J.
-
supporting information; experimental part
p. 7310 - 7312
(2012/07/31)
-
- CuI-Catalyzed 11C carboxylation of boronic acid esters: A rapid and convenient entry to 11C-labeled carboxylic acids, esters, and amides
-
Rapid and direct: The carboxylation of boronic acid esters with 11CO2 provides [11C]carboxylic acids as a convenient entry into [11C]esters and [11C]amides (see scheme). This conversion of boronates is tolerant to diverse functional groups (e.g., halo, nitro, or carbonyl). Copyright
- Riss, Patrick J.,Lu, Shuiyu,Telu, Sanjay,Aigbirhio, Franklin I.,Pike, Victor W.
-
supporting information; experimental part
p. 2698 - 2702
(2012/04/17)
-
- Labeling approaches for the GE11 peptide, an epidermal growth factor receptor biomarker
-
The epidermal growth factor receptor (EGFR) is involved in the proliferation and differentiation of normal and malignant cells and is a major therapeutic target for a variety of human cancers. The peptide GE11 was reported to bind efficiently to the EGFR.
- Dissoki, Samar,Hagooly, Aviv,Elmachily, Smadar,Mishani, Eyal
-
experimental part
p. 693 - 701
(2012/07/27)
-
- FORMATION OF 18F AND 19F FLUOROARENES BEARING REACTIVE FUNCTIONALITIES
-
An iodonium compound of formula (I): where RAR1 is a C5-6 aryl group, bearing at least one substituent selected from formyl, thionoacyl, acylamidocarboxy, thionoester, azo, C2-20 alkenyl, C2-20 alkynyl, and (CH
- -
-
Page/Page column 7
(2009/12/05)
-
- Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl carbamate analogs as σ2 receptor ligands
-
A series of N-substituted 9-azabicyclo[3.3.1]nonan-3α-yl phenylcarbamate analogs was prepared and their affinities for sigma (σ1 and σ2) receptors were measured in vitro. The results of their structure-activity relationship study ide
- Vangveravong, Suwanna,Xu, Jinbin,Zeng, Chenbo,Mach, Robert H.
-
p. 6988 - 6997
(2007/10/03)
-
- N-hydroxysuccinimide-promoted oxidation of primary alcohols and aldehydes to form active esters with hypervalent(III) iodine
-
A simple, mild, and efficient method for the conversion of primary alcohols and aldehydes to N-hydroxysuccinimide esters with (diacetoxyiodo)benzene in high yield is developed. N-Hydroxysuccinimide acts not only as an esterification partner but also as an activator of PhI(OAc)2 in this reaction. Copyright
- Wang, Naiwei,Liu, Renhua,Xu, Qing,Liang, Xinmiao
-
p. 566 - 567
(2007/10/03)
-
- Synthesis and liposome encapsulation of a novel 18F-conjugate of ω-conotoxin GVIA for the potential imaging of N-type Ca2+ channels in the brain by positron emission tomography
-
ω-Conotoxin GVIA is a potent, irreversible antagonist of N-type voltage gated Ca2+ channels. A radiofluorinated analogue of GVIA could be useful in assessing regional synaptic density of the brain, in vivo, using positron emission tomography. N
- Azarian, Vahe,Gangloff, Anne,Seimbille, Yann,Delaloye, Sibylle,Czernin, Johannes,Phelps, Michael E.,Silverman, Daniel H. S.
-
p. 269 - 283
(2007/10/03)
-
- Novel synthesis of [18F]-fluorobenzene and pyridinecarbohydrazide-folates as potential PET radiopharmaceuticals
-
In an attempt to visualize folate receptors that over-express on many cancers, [18F]-fluorobenzene and pyridine carbohydrazide-folates were synthesized using two different synthetic approaches starting from nucleophilic displacement reactions on ethyl-trimethylammonium-benzoate and pyridine carboxylate precursors. The intermediates ethyl [18F]-fluorinated benzene and pyridine esters were reacted with hydrazine to produce the [ 18F]-fluorobenzene and pyridine carbohydrazides followed by coupling with NHS-folate 11 in the first approach. Whereas hydrazide-folate 5 was reacted with 2,5-dioxoazolidinyl [18F]-fluorobenzenecarboxylate in the second approach. Based on starting [18F]-fluoride, radiochemical yields and synthesis times were found to be around 80% (45 min) and 35% (80 min) for the first and the second approaches, respectively. The first synthetic approach holds considerable promise as a rapid and simple method for the radiofluorination of folic acid with high radiochemical yield and short time. Copyright
- Al Jammaz,Al-Otaibi,Okarvi,Amartey
-
p. 125 - 137
(2007/10/03)
-