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1.
The present study describes a rapid synthesis method for labeled [11C]FK506 for positron emission tomography (PET). A one-pot reaction from [11C]CH3I, involving a Wittig reaction as the key carboncarbon bond formation was developed. The chemical process was accomplished using a designed, fully automated synthetic apparatus, and an injectable solution of [11C]FK506 was obtained in only 34 min from [11C]CH3I. The decay-corrected radiochemical yield based on [11C]CH3I was 11.9%, and the specific activity was 39.8 GBq/μmol.  相似文献   

2.
《Tetrahedron》2019,75(29):3917-3922
Recently [11C]mG4P012 (previously [11C]KALB012 and presently named as [11C]PXT012253 by Prexton Therapeutics) had been used as a biomarker during the preclinical development of a potential therapeutic drug, PXT0002331 (an mGluR4 PAM), for PD and l-dopa-induced dyskinesia. [11C]mG4P012 was shown to be a promising PET radioligand for mGluR4 in the monkey brain and for further development in human subjects. However, the previously reported multi-step synthesis of the thiophenol precursor suffered from low yields and difficult workup procedures. To support the translational research of [11C]mG4P012 and the other potential applications, we have developed a new route for synthesis of the thiophenol precursor and optimized the reaction conditions. The synthesis of N-(4-chloro-3-mercaptophenyl)picolinamide from 1-chloro-4-nitrobenzene has been greatly improved from 8% to 52% total yield with easy handling and in gram scales.  相似文献   

3.
Carbon-11-labeled nimesulide analogs, N-[11C]methyl-N-(2-benzyloxy-4-nitrophenyl)methanesulfonamide ([11C]4a), N-[11C]methyl-N-[2-(4′-methylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]4b), N-[11C]methyl-N-[2-(4′-fluorobenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]4c), N-[11C]methyl-N-[2-(4′-nitrobenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]8a), N-[11C]methyl-N-[2-(β-naphthylmethoxy)-4-nitrophenyl]methanesulfonamide ([11C]8b), and N-[11C]methyl-N-[2-(2′-phenylbenzyloxy)-4-nitrophenyl]methanesulfonamide ([11C]8c), have been synthesized as new potential positron emission tomography (PET) selective aromatase expression regulator (SAER) radiotracers for imaging of aromatase expression in breast cancer. The target tracers were prepared by N-[11C]methylation of their corresponding precursors using [11C]CH3OTf under basic conditions (NaH) and isolated by reversed-phase high-pressure liquid chromatography (HPLC) method in 30–50% radiochemical yields decay corrected to end of bombardment (EOB) with 25–30 min overall synthesis time and 111–148 GBq/μmol specific activity at end of synthesis (EOS).  相似文献   

4.
We have synthesized deuterium and carbon-14 labeled enantiomerically pure octahydroindole-2-carboxylic acid (PD0140417), N-methyl octahydroindole-2-carboxylic acid (PD0348183) and their racemic analogs (PD0108405 and PD0338055). [ring-U-14C]PD0140417 was prepared from [ring-U-14C]benzoic acid in a seven-step synthesis in 6.2% overall radiochemical yield. [14C]PD0348183 was prepared from [14C]BaCO3 in a five-step synthesis in 16% radiochemical yield. Additionally, [D]PD0108405 and [D]PD0338055 were synthesized by direct platinum-catalyzed hydrogenation with deuterium gas.  相似文献   

5.
For in vivo receptor studies N-[11C]methyl-2,5-dimethoxy-4-bromo-amphetamine, [11C]MDOB, was synthesized by the reaction of [11C]CH3I with DOB in acetonitrile. The labelling yield was determined in dependence on amount of precursor, time and temperature of the methylation reaction. During 10 to 15 minutes 60% to 70% of [11C]MDOB has been obtained at 110°C.  相似文献   

6.
β-(N-Benzoylamino)methacrylamide, a key intermediate for the preparation of [2-11C]thymine, was synthesized in three steps from ethyl α-formylpropionate and NH3. Reaction of the alkali metal salts of β-(N-benzoylamino)methacrylamide with [11C]phosgene gave [2-11C]thymine. The yield of [2-11C]thymine was 362 ± 53 MBq at EOS (n = 3) (18 MeV proton beam; 10 μA, 10 min). The total synthesis was accomplished in just 16 min from the end of bombardment.  相似文献   

7.
In order to evaluate the neurobiological mechanism causing the psychogenic effects of N-methyl-2,5-dimethoxy-4-methylamphetamine (MDOM), the11C labelled analogue was prepared for application in in vivo PET studies by the reaction of 2,5-dimethoxy-4-methylamphetamine (DOM) with [11C]CH3I. The radiochemical yield was determined in dependence on time, temperature, solvent and amount of substrate. The best conditions for fast labelling reactions with11C on a preparative scale were found to be a reaction time of 10 miutes at 110°C using 1 mg DOM in acetonitrile thus obtaining radiochemical yields of 80% (based on produced [11C]CH3I).  相似文献   

8.
The Stille cross-coupling reaction of [1-11C]acetyl chloride with tributylphenylstannane leading to [carbonyl-11C]acetophenone was studied with the goal of developing a new 11C-labeling method for positron emission tomography tracer synthesis. The coupled product [carbonyl-11C]acetophenone was synthesized using the Pd2(dba)3/P(MeNCH2CH2)3N·HCl system with a 60-61% radiochemical conversion from [1-11C]acetyl chloride (decay-corrected, n = 3).  相似文献   

9.
Hydrogen [11C]cyanide ([11C]HCN) is a versatile 11C-labelling agent for the production of 11C-labelled compounds used for positron emission tomography (PET). However, the traditional method for [11C]HCN production requires a dedicated infrastructure, limiting accessibility to [11C]HCN. Herein, we report a simple and efficient [11C]HCN production method that can be easily implemented in 11C production facilities. The immediate production of [11C]HCN was achieved by passing gaseous [11C]methyl iodide ([11C]CH3I) through a small two-layered reaction column. The first layer contained an N-oxide and a sulfoxide for conversion of [11C]CH3I to [11C]formaldehyde ([11C]CH2O). The [11C]CH2O produced was subsequently converted to [11C]HCN in a second layer containing hydroxylamine-O-sulfonic acid. The yield of [11C]HCN produced by the current method was comparable to that of [11C]HCN produced by the traditional method. The use of oxymatrine and diphenyl sulfoxide for [11C]CH2O production prevented deterioration of the molar activity of [11C]HCN. Using this method, compounds labelled with [11C]HCN are now made easily accessible for PET synthesis applications using readily available labware, without the need for the ‘traditional’ dedicated cyanide synthesis infrastructure.

In a reaction column, gaseous [11C]methyl iodide was converted to [11C]formaldehyde in a first layer containing N-oxide and then transformed into hydrogen [11C]cyanide in a second layer containing hydroxylamine-O-sulfonic acid within 2 minutes.  相似文献   

10.
The14N/p, /11C-reaction was studied in different N2/H2-mixtures. The products are [11C]-CO2, [11C]-CO and [11C]-CH4. The yield ratio may be controlled by varying the bombardment conditions. High pressure, high H2-content, high beam current and high proton energy shift the ratio towards [11C]-CH4. Lower beam current and lower proton energy increase the yield of [11C]-CO2. The production of [11C]-CO is constant over a wide range of conditions /about 10%/. For the production of [11C]-CH4 in good yield a target gas holder for high pressures has been developed. Details are given in Fig. 7. This target gas holder was filled with 5% H2 in N2 at 3×106 Pa. Proton irradiation of the mixture gives a typical yield of [11C]-CH4 of 400–500 mCi at a beam current of 15–20 A within 20 min. Only traces of other11C-labelled compounds could be detected under these conditions.  相似文献   

11.
In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA),2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6)4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA)1 and 2-methyl-4,5-methylenedioxyamphetamine3 with [11C]CH3I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors1 or3, thus obtaining radiochemical yields of 60% (based on produced [11C]CH3I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [11C]MDMA in contrast to a ratio of 3.7 for [11C]MADAM-6.  相似文献   

12.
Effective methods are needed for labelling acyclic ureas with carbon-11 (t1/2=20.4 min) as potential radiotracers for biomedical imaging with positron emission tomography (PET). Herein, we describe the rapid and high-yield syntheses of unsymmetrical acyclic [11C]ureas under mild conditions (room temperature and within 7 min) using no-carrier-added [11C]carbonyl difluoride with aliphatic and aryl amines. This methodology is compatible with diverse functionality (e. g., hydroxy, carboxyl, amino, amido, or pyridyl) in the substrate amines. The labelling process proceeds through putative [11C]carbamoyl fluorides and for primary amines through isolable [11C]isocyanate intermediates. Unsymmetrical [11C]ureas are produced with negligible amounts of unwanted symmetrical [11C]urea byproducts. Moreover, the overall labelling method tolerates trace water and the generally moderate to excellent yields show good reproducibility. [11C]Carbonyl difluoride shows exceptional promise for application to the synthesis of acyclic [11C]ureas as new radiotracers for biomedical imaging with PET.  相似文献   

13.
The temperature dependence of the rate of the reaction of OH with 2-(dimethylamino)-ethanol, (CH3)2NCH2CH2OH (DMAE) was investigated over the temperature range, 234 to 364 K. The reaction was studied using the flash photolysis-resonance fluorescence technique. The room temperature rate constant determined for this reaction was (10.3 ± 2.0) × 10?11 cm3 molecule?1 s?1, with essentially no temperature dependence evident within the uncertainty in the experiments. A value of (9.0 ± 2.0) × 10?11 cm3 molecule?1 s?1 is believed to best describe the reaction over the entire temperature range. The room temperature rate constant is about twice the value reported previously for this reaction. The overall reaction of OH with DMAE was apportioned to the reactivity of OH for abstracting individual H- atoms from different types of C? H bonds and the O? H bond within the molecule. This technique predicts the overall rate constant for the OH-DMAE reaction to within about 15% of the experimental value and makes it possible to estimate the yields of the initial radical products of the OH attack on DMAE. A mechanism is proposed for the subsequent atmospheric reactions that would occur in the photooxidation of DMAE.  相似文献   

14.
Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2‐arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti‐inflammatory drugs (NSAIDs). Thus, we developed a novel 11C‐radiolabeling methodology based on rapid C‐[11C]methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One‐pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C‐incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)‐induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C‐labeling of 2‐arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.  相似文献   

15.
1-Amino-3-methoxypropane (3MPA) and 2-dimethylaminoethanol (DMAE) are potential volatile amines for boiler water treatment and were investigated for their complexation behaviour with copper. Their pKb values were 3.67 and 4.52 at 25°C and they formed coloured complexes with absorption in the region of 644 and 510 nm, respectively. In the pH range 10–11, the Cu-3MPA complex exhibited stepwise reduction and [Cu(3MPA)2]+ was identified, with a stability constant of 109.52. In the pH range 8–10.5, the Cu-DMAE complex exhibited 2e? reduction and the species [Cu(DMAE)2(OH)2] was identified, with a stability constant of 1020.39. A correlation between visible and ESR spectra and reduction behaviour was established.  相似文献   

16.
N-[11C]methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine ([11C]MBDB) 3 was prepared by methylation of the demethyl precursor BDB with [11C]CHI. The radiosynthesis was optimized with regard to temperature, reaction time and amount of precursor, best results (i.e., 84% radiochemical yield, based on [11C]CH3I activity) were obtained using 3 mg BDB at a reaction temperature of 130 °C in 8 minutes. With respect to a facilitated workup routine, productions were performed with 0.6 mg BDB at 110 °C for 10 minutes, yielding more than 50% of 3. The radiochemical purity of the final tracer solution was >98%, the specific activity was determined to be 300 GBq/mol (8000 Ci/mmol). Biodistribution, studies in rats showed two major metabolic pathways as indicated by an increasing liver uptake (9.1% ID/organ at 5 minutes to 21% ID/organ at 30 minutes) and a high urine activity (up to 16% ID/g). In brain tracer uptake was more than 1%, with a brain to blood ratio of almost 12 resulting from a very rapid blood clearance of 3.  相似文献   

17.
A new flow-through system for the production of [11C]phosgene, a versatile labelling agent in radiochemistry for PET, is described. Cyclotron-produced [11C]CH4 is mixed with Cl2 and converted into [11C]CCl4 by passing the mixture through an empty quartz tube at 510 °C. The outflow is directed through a Sb-filled guard that takes out Cl2 and then, without intentional O2 addition, through a second empty quartz tube at 750 °C, giving rise to [11C]phosgene in 30–35% radiochemical yield.  相似文献   

18.
The progress of positron emission tomography goes together with an increasing demand for new radiopharmaceuticals: among these, the development of radiopharmaceuticals labelled with carbon-11 is particularly interesting because these compounds are biologically indistinguishable from their stable analogues. These radiotracers are prepared starting from [11C]carbon dioxide, the most common and versatile primary labelling precursor, or from secondary labelling precursors such [11C]methyl iodide produced by “wet” or “gas-phase” method. The gas-phase is the most used method and consists in the radical reaction of iodine vapours with [11C]methane, produced in target or from [11C]carbon dioxide by reduction with hydrogen on nickel catalyst at high temperature. This second approach is frequently adopted in commercial automatic methylation modules, such as the TRACERlab FX C. When not performed in target, [11C]CH4 production represents a key step for the [11C]CH3I synthesis from which the outcome of the whole radiolabelling process depends. In order to improve the performance of the module, a new reduction catalyst made of a mixture of metallic Ni (nanopowder) and molecular sieves mixed in different ratios has been tested. Preliminary results demonstrated that not only the mixture of nanopowder-Ni and molecular sieves represents a valid reduction catalyst but also permits to trap [11C]CO2 and subsequently use it as labelling reagent, making TRACERlab FX C a module for both methylation and carboxylation.  相似文献   

19.
Incorporation experiments with (3H and 14C) doubly labelled farnesols into cantharidin After injection of 11′, 12-[3H]-7-[14C]-farnesol or 11′, 12-[3H]-5,6-[14C]-farnesol, the 3H-label is located specifically in the C(9)-methyl-group of cantharidin, whereas the 14C-labelling pattern follows an incorporation via acetic acid (Scheme 4). C-Atoms 5, 6 and 7 from the middle part of the farnesol molecule are utilized for cantharidin biosynthesis to an extent that is about 2.1–11% of the incorporation rate of the methyl groups C(11′) and C(12), depending on the position of the 14C-label in farnesol. These results confirm our earlier hypothesis [1] that the C10-molecule cantharidin is biosynthesized from the C15-precursor farnesol which is cleaved between C(1)–C(2), C(4)–C(5), and C(7)–C(8). The synthesis of 7-[14C]-farnesol and of 5,6-[14C]-farnesol is described.  相似文献   

20.
We developed a new one-pot reaction of phenolic acids to afford the corresponding esters and amides through acyl-protected and activated phenolic acid intermediates. The simultaneous protection/activation of phenolic acids with alkylchloroformates proceeded readily in the presence of DMAP at room temperature; subsequent addition of alcohols or amines afforded the corresponding esters or amides. The use of iso-butyloxycarbonyl as the protecting and activating group in the one-pot reactions afforded phenolic esters or amides in 91% average yield. As a practical example of this convenient synthesis, caffeic acid phenethyl ester (CAPE) was readily synthesized from commercially available caffeic acid and phenethyl alcohol in 95% yield, and an isotopomer of CAPE, [3,10-13C2]CAPE, was synthesized in 91% yield from [3-13C]caffeic acid and 2-[1-13C]phenethyl alcohol. This method may be useful for the convenient esterification and amidation of diverse phenolic acids.  相似文献   

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