JOURNAL OF ORGANIC CHEMISTRY
·
2023
·
IF 3.6
Fenfen Xie,Fen Han,Yunying Yan,Haiqiong Li,Jianjun Hao,Linhai Jing,Pan Han
It is significant to develop novel difluoromethylation methods because of the important roles of difluoromethyl groups in the medicinal chemistry and material industries. Here, we developed a novel difluoromethylation–carboxylation and difluoromethylation–deuteration method triggered by a difluoromethyl radical generated by electroreduction of stable and easily available difluoromethyltriphenylphosphonium bromide. Various molecules containing difluoromethyl and carboxyl or deuterium groups can be synthesized through this method. The establishment of this method will provide an alternative to radical difluoromethylation reactions.
研究领域:
有机化学
·
药物化学
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DOI
PubMed
高影响因子
BIOPHARMACEUTICS & DRUG DISPOSITION
·
2023
·Vol. 44
·期 2
·165-174
·
IF 2.1
Xuyi Zhan,Shaoyin Bao,Xumei Li,Shaojun Zhou,Maha Raja Dahar,Nengming Lin,Xiugui Chen,Chengshan Niu,Kaige Ji,Yusheng Wu,Kui Zeng,Zhihua Tang,Lushan Yu
Osimertinib is a highly selective third-generation irreversible inhibitor of epidermal growth factor receptor mutant, which can be utilized to treat non-small cell lung cancer. As the substrate of cytochrome P450 enzyme, it is mainly metabolized by the CYP3A enzyme in humans. Among the metabolites produced by osimertinib, AZ5104, and AZ7550, which are demethylated that is most vital. Nowadays, deuteration is a new design approach for several drugs. This popular strategy is deemed to improve the pharmacokinetic characteristics of the original drugs. Therefore, in this study the metabolism profiles of osimertinib and its deuterated compound (osimertinib-d3) in liver microsomes and human recombinant cytochrome P450 isoenzymes and the pharmacokinetics in rats and humans were compared. After deuteration, its kinetic isotope effect greatly inhibited the metabolic pathway that produces AZ5104. The plasma concentration of the key metabolite AZ5104 of osimertinib-d3 in rats and humans decreased significantly compared with that of the osimertinib. This phenomenon was consistent with the results of the metabolism studies in vitro. In addition, the in vivo results indicated that osimertinib-d3 had higher systemic exposure (AUC) and peak concentration (C max ) compared with the osimertinib in rats and human body.
研究领域:
药理学
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肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2024
·
IF 3.3
Hui Xu,Zhi-Jiang Jiang,Yun Jia,Yuhang Su,Jian-Fei Bai,Zhanghua Gao,Jia Chen,Kun Gao
Aromatic sulfones are the prevailing scaffolds in pharmaceutical and material sciences. However, compared to their widespread application, the selective deuterium labeling of these structures is restricted due to their electron-deficient properties. This study presents two comprehensive strategies for the deuteration of aromatic sulfones. The base-promoted deuteration uses DMSO-d6 as the deuterium source, resulting in a rapid H/D exchange within 2 h. Meanwhile, a silver-catalyzed protocol offers a much milder option by using economical D2O to furnish the labeled sulfones.
研究领域:
药物化学
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材料科学
·
有机合成
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Jinfeng Zheng,Jianbo Tang,Shenhao Jin,Hao Hu,Zhi-Jiang Jiang,Jia Chen,Jian-Fei Bai,Zhanghua Gao
An efficient method has been developed for the synthesis of α-deuterated α-amino esters via hydrogen isotope exchange of α-amino esters in D2O with 2-hydroxynicotinaldehyde as a catalyst under mild conditions. This methodology exhibits a wide range of substrate scopes, remarkable functional group tolerance, and affording the desired products in good yields with excellent deuterium incorporation. Notably, the ortho-hydroxyl group and the pyridine ring of the catalyst play a crucial role in the catalytic activity, which not only stabilizes the carbon-anion intermediates but also enhances the acidity of the amino esters’ α–C–H bond.
研究领域:
有机化学
·
合成化学
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DOI
PubMed
高影响因子
Energetic Materials Frontiers
·
2023
·
IF 0
Zheng-hang Luo,Jia-jun Zhou,Hao Li,Yuan-hua Xia,Liang-fei Bai,Hai-jun Yang
The deuteration of energetic materials contributes to high signal-to-noise ratios (SNRs) in neutron diffraction, thus allowing the structures of energetic materials to be effectively investigated. This study developed the synthesis methods of deuterated energetic materials through chemical synthesis or newly developed one-pot H/D exchange. Using these methods, it synthesized nine deuterated energetic materials in a concise and low-cost manner: deuterated 1,3,5-triamino-2,4,6-trinitrobenzene (TATB- d 6 , 1 ), 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX- d 8 , 2 ), 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX- d 6 , 3 ), dihydroxylammonium 5,5′-bis(tetrazole-1-oate) (TKX-50- d 8 , 4 ), nitroguanidine (NQ- d 4 , 5 ), 1,1-diamino-2,2-dinitroethylene (FOX-7- d 4 , 6 ), 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105- d 4 , 7 ), trinitrotoluene (TNT- d 3 , 8 ), and 3-nitro-1,2,4-triazol-5-one (NTO- d 2 , 9 ). Furthermore, the single crystals of HMX- d 8 ( 2 ) and RDX- d 6 ( 3 ) were obtained, and the α- , β- , γ- , and δ- polymorphs of HMX- d 8 ( 2 ) were prepared accordingly. The deuterated energetic materials were characterized and analyzed using infrared spectroscopy (IR), nuclear magnetic resonance (NMR) spectroscopy, differential scanning calorimetry (DSC), thermogravimetry (TG), X-ray diffraction (XRD), and neutron diffraction. Besides, this study determined the decomposition activation energy ( E a ), pre-exponential factor (A), decomposition rate constant ( k ), and critical explosion temperature ( T b ) of TATB- d 6 ( 1 ), HMX- d 8 ( 2 ), and RDX- d 6 ( 3 ) via DSC experiments at different heating rates. The NMR and neutron diffraction data show that these deuterated energetic materials have high deuteration rates of more than 95%. The DSC and TG analyses indicate that the deuterated energetic materials exhibit slightly higher decomposition temperatures than their nondeuterated counterparts. Furthermore, neutron diffraction shows that the deuterated energetic materials feature high SNRs.
研究领域:
化学
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材料科学
·
物理学
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DOI
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Sheng-Hua Li,Tuo-Yu Zhou,Shu-Yue Yang,Tai-Wen Li,Penglin Zhang,Guang-Yue Li,Chang Li,Hong-Qiao Li,Jing-Yi Li,Qian Zhao
The development of large-scale manufacture for low-cost afterglow materials is critical for their applications and industrializations. Herein, we presented the organic–inorganic afterglow materials with multiple colors based on boric acid (BA) and aromatic dicarboxylic acids or their diesters. These hybrid materials were facilely prepared by a solution-processable method via evaporating the solvent of the BA and organics solution at room temperature. The crystalized BA provided a rigid surrounding for the organics via hydrogen bonds, which effectively inhibited the non-radiative decay of triplet excitons and gave efficient and persistent room temperature afterglow with the phosphorescent quantum yield up to 57.66%. The phosphorescence properties were almost unchanged when deuterated BA was used instead of BA, indicating the deuteration of the hydrogen bond would not suppress the non-radiative decay from the excited state. Furthermore, a phosphorescence resonance energy transfer process was achieved by introducing 4-[4-(Dimethylamino)styryl]-1-methylpyridinium iodide (DASPI) as the energy acceptor. These BA based system could be used as quick-writable phosphorescent inks for multifunctional applications, such as anti-counterfeiting, information storage, encryption, and even for phosphor layer of light emitting diode. These results not only strengthen the understanding of the luminescence mechanism of BA hybrid materials, but also provide a new access to organic–inorganic afterglow materials.
研究领域:
材料科学
·
光学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
·
2021
·
IF 4.354
Junhua Kong,Zhi-Jiang Jiang,Jiayuan Xu,Yan Li,Hong Cao,Yanan Ding,Bencan Tang,Jia Chen,Zhanghua Gao
A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation–deprotonation process.
研究领域:
有机化学
·
同位素化学
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产品关联
DOI
PubMed
高影响因子
Current Pharmaceutical Analysis
·
2023
·Vol. 19
·期 4
·282-288
·
IF 0.6
Zhang Hanzhi,Qin Feng,Sun Ning,Zheng Mengmeng,Luo Wenyan,Qiu Ya,Liu Hao,Zhang Xiangmin
Background: After the hydrolysis of daptomycin in deuterated hydrochloric acid, the deuterium-substituted kynurenine was found, but the structure of deuterium-substituted kynurenine has not been reported. Introduction: The deuterium-substituted kynurenines were simply synthesized
and confirmed to be tri- and tetra-substituted products by high resolution mass spectrum and NMR. In further, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and high
performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLCQ/ TOF-MS). Methods: In the present study, a simple synthesis method was developed for deuteriumsubstituted kynurenine, and its structure was confirmed by high resolution mass spectrometry and NMR. L-kynurenine
was mixed with the deuterated hydrochloric acid and heated at 110 °C for 7 h. The hydrogen/deuterium exchange products of L-kynurenine were obtained through the hydrogen/deuterium exchange method. After the derivation of deuterium-substituted L-kynurenine by Marfey’s reagent, the
conformation of kynurenine in daptomycin was deduced by HPLC-Q/TOF-MS. Results: The deuterium-substituted kynurenines were confirmed to be tri- and tetra-substituted products by high resolution mass spectrum. Further, Hydrogen NMR spectrum indicated that the deuterium-substitution positions
were β-position on amino acid and 3’ and 5’ positions on the benzene ring. Thus, the tri-deuterium-substituted product was L-[β, 3’, 5’-2H3] kynurenine-d3, while the tetra-deuterium-substituted product was L-[β, β, 3’,
5’-2H4] kynurenine-d4. Furthermore, the deuterium-substituted kynurenines were used to determine the conformation of kynurenine to be L-type in daptomycin through conformation analysis combined with derivation and HPLC-Q/TOF-MS. Conclusion: The synthesis, structures,
and application of tri- or tetra- deuterium-substituted kynurenine were reported in this study.
研究领域:
生物化学
·
药物化学
·
分析化学
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DOI
高影响因子
POLYMER
·
2022
·
IF 4.432
Xinxin Tan,Jie Du,Yiliu Liu,Jingwen Ba,Xiaoyu Yang,Xiwen Yang,Meifang Liu,Wenhua Luo
Deuterated polymers have been widely used in many researches, such as small-angle neutron scattering, NMR studies and inertial confinement fusion, but the types of deuterated polymers that can be used are still very limited. In this work, we introduce the concept of supramolecular polymers to develop new deuterated materials toward applications in inertial confinement fusion. To this end, cycloocene- d 14 with deuterium content of 97% is prepared and has been further used as monomers . Deuterated macromonomers with 2-ureido-pyrimidinone as end groups are prepared via either a multistep or a “one-pot” approach. The supramolecular deuterated polymers are formed by the hydrogen-bonding mediated supramolecular polymerization of the macromonomers. With the obtained supramolecular deuterated polymers, uniform polymer shells toward ICF experiments are prepared by the microfluidic technique and solvent evaporation method.
研究领域:
材料科学
·
核物理学
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DOI
高影响因子
JOURNAL OF NUCLEAR MATERIALS
·
2020
·
IF 2.485
Meifang Liu,Yueqing Zheng,Qiang Chen,Yuguang Wang,Yiyang Liu,Jing Li,Jie Li,Yawen Huang,Qiang Yin
Deuterated polymer beads with specifications on their size and structure are needed for preparing the targets in the inertial confined fusion experiments. Driven by the need to fabricate these beads meeting physical design, the coflow microfluidic device composed of glass round capillaries were fabricated. The formation mechanism of the droplets of the polymer solution (O droplets), the vacuole formation in the polymer beads and the size relationship between the O droplets and the resulting polymer beads were also investigated. The diameter of the O droplets can be controlled by designing microfluidic device with appropriate capillaries and tuning the flow rate of the polymer solution and aqueous solution. Residual solvent in polymer beads was reduced by optimizing the solidifying and drying process, leading to the decrease of the vacuoles. The size relationship between the initial O droplets and the resulting beads was revealed and confirmed. Consequently, monodisperse polymer beads such as ∼480 μm and ∼700 μm poly (α-methylstyrene), ∼700 μm polystyrene and ∼800 μm deuterated polystyrene beads meeting physical design were successfully prepared, which can be used to prepare the target in the inertial confined fusion experiments. It demonstrated the technical feasibility of controlling the bead size, providing a promising approach to fabricate the polymer beads meeting size requirement.
研究领域:
材料科学
·
核物理
·
化学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS
·
2018
·Vol. 61
·期 14
·1043-1047
·
IF 1.423
Wulian Chen,Chaomin Zhao,Xiaojun Deng
An efficient and simple synthetic route of deuterium-labeled 2-quinoxalinecarboxylic acid- d 4 (QCA- d 4 ) and 3-methylquinoxaline-2-carboxylic acid- d 4 (MQCA- d 4 ) is presented with 99.9% and 99.6% isotopic enrichment using aniline- d 5 as labeled starting material. Their chemical structures were confirmed by 1 H NMR, and their isotopic abundance was determined by mass spectrometry analysis.
研究领域:
有机化学
·
药物化学
✓ 已验证
DOI
高影响因子
Crystals
·
2020
·Vol. 10
·期 6
·511
·
IF 2.404
Xueni Liu,Yan Ren,Cheng Qian Zhang,Bo Wang,Sheng Qing Xia
Single-crystalline fibers have distinct structures and optical properties comparing with the bulk crystals. In this article, two types of single-crystalline fibers of deuterated potassium dihydrogen phosphate (K(H1−xDx)2PO4,DKDP) are obtained by rapid growth in room-temperature supersaturated solution. X-ray diffraction analysis reveals that these DKDP single-crystalline fibers belong to tetragonal (I-42d) and monoclinic (P21/c) phases, respectively. The crystal structure of the tetragonal DKDP single-crystalline fiber is identical to that of the bulk DKDP tetragonal crystal reported. The lattice parameters of the monoclinic DKDP fiber (with the deuterium content of 55%) are a = 14.6571 Å, b = 4.5187 Å, c = 18.6962 Å, and β = 108.030°, which is a new crystal phase of DKDP. The monoclinic DKDP single-crystalline fiber is metastable at the present experimental condition and readily transit to the corresponding DKDP tetragonal phase in solution and in solid by grinding. The optical experiment shows that the highly deuterated tetragonal DKDP single-crystalline fiber possesses excellent optical guided-wave and effective second-harmonic generation properties. DKDP single-crystalline fibers are expected to be the suitable candidates for fabrication of the miniaturized nonlinear optical devices.
研究领域:
材料科学
·
光学
✓ 已验证
DOI
高影响因子
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