Co-reporter:Zeqiong Yu, Shaowei Bo, Huiyuan Wang, Yu Li, Zhigang Yang, Yongzhuo Huang, and Zhong-Xing Jiang
Molecular Pharmaceutics October 2, 2017 Volume 14(Issue 10) pp:3473-3473
Publication Date(Web):August 22, 2017
DOI:10.1021/acs.molpharmaceut.7b00496
Polydisperse PEGs are ubiquitously used in pharmaceutical industry and biomedical research. However, the monodispersity in PEGs may play a role in the development of safe and effective PEGylated small molecular drugs. Here, to avoid the polydispersity in polidocanol, the active ingredient in a clinically used drug, a macrocyclic sulfate-based strategy for the efficient and scalable synthesis of monodisperse polidocanols, their sulfates, and their methylated derivatives, was developed. TLC and HPLC analysis indicated a complex mixture in regular polidocanol and high purities in monodisperse polidocanols and their derivatives. Assay on HUVEC, L929, and HePG2 cells showed that monodisperse polidocanols have much higher cytotoxicity and safety than that of regular polidocanol. It was found that the monodispersity of PEGs in polidocanols is crucial for achieving the optimal therapeutic results. Therefore, based on this case study, it would be beneficial to optimize PEGylated small molecular drugs with monodisperse PEGs in pharmaceutical research and development.Keywords: monodisperse; PEGylated drugs; polidocanol; polydisperse; polyethylene glycols (PEGs);
Co-reporter:Qiaoli Peng;Yaping Yuan;Huaibin Zhang;Shaowei Bo;Yu Li;Shizhen Chen;Zhigang Yang;Xin Zhou
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 30) pp:6441-6446
Publication Date(Web):2017/08/02
DOI:10.1039/C7OB01068K
For detecting metal ions with 19F chemical exchange saturation transfer magnetic resonance imaging (19F CEST MRI), a class of novel fluorinated chelators with diverse fluorine contents and chelation properties were conveniently synthesized on gram scales. Among them, a DTPA-derived chelator with high sensitivity and selectivity was identified as a novel 19F CEST imaging probe for simultaneously detecting multiple metal ions.
Co-reporter:Haotian Xing, Long Chen, Yimin Jia, Zhongxing Jiang, Zhigang Yang
Tetrahedron Letters 2017 Volume 58, Issue 23(Issue 23) pp:
Publication Date(Web):7 June 2017
DOI:10.1016/j.tetlet.2017.04.053
•A Fe2O3-catalyzed Pummerer rearrangement was explored.•Applications of the method led to a series of important alkylthiomethyl molecules.•The product structure was further confirmed by X-ray analysis of its single crystal.A simple, effective approach for the Pummerer rearrangement of acyl chlorides with sulfoxides by using a low-cost and more abundant Fe catalyst has been described. The alkylthiomethyl ester products were prepared in good to excellent yields for a range of different substrates including asymmetrical sulfoxides and acyl chlorides with a variety of functional groups under mild reaction conditions. The reaction features short reaction time, simple manipulation, cheap reagents and a broad substrate scope. Single crystal X-ray analysis of a representative methylthiomethyl (MTM) group containing product was also reported.Download high-res image (49KB)Download full-size image
Co-reporter:Xin Liu;Yaping Yuan;Shaowei Bo;Yu Li;Zhigang Yang;Xin Zhou;Shizhen Chen
European Journal of Organic Chemistry 2017 Volume 2017(Issue 30) pp:4461-4468
Publication Date(Web):2017/08/17
DOI:10.1002/ejoc.201700566
Monitoring a drug-delivery system with an imaging modality is of great importance for detailed understanding of drug-delivery processes and for achieving optimal therapeutic effects. Here, novel fluorinated self-assembled dendrimers with a single 19F NMR signal were conveniently synthesized on multigram scales, and 19F magnetic resonance, including spectroscopy (19F NMR) and imaging (19F MRI), was used to monitor the fluorinated dendrimer-based self-assembled drug-delivery systems. It was found that 19F NMR and 19F MRI were convenient and sensitive tools to monitor the self-assembly and drug-loading processes and to detect weak interactions between the drug and the drug-delivery vehicle because changes in the self-assembly profile sensitively induced corresponding 19F magnetic resonance responses.
Co-reporter:Qiuyan Shi, Yu Li, Shaowei Bo, Xiaofei Li, Peng Zhao, Qi Liu, Zhigang Yang, Hengjiang Cong, Hexiang Deng, Mingnan Chen, Shizhen Chen, Xin Zhou, Hong Ding and Zhong-Xing Jiang
Chemical Communications 2016 vol. 52(Issue 29) pp:5136-5139
Publication Date(Web):10 Mar 2016
DOI:10.1039/C6CC01508E
Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and 19F MRI sensitivity was discovered as a novel theranostic agent.
Co-reporter:Qiuyan Shi, Yu Li, Shaowei Bo, Xiaofei Li, Peng Zhao, Qi Liu, Zhigang Yang, Hengjiang Cong, Hexiang Deng, Mingnan Chen, Shizhen Chen, Xin Zhou, Hong Ding and Zhong-Xing Jiang
Chemical Communications 2016 vol. 52(Issue 45) pp:7314-7314
Publication Date(Web):18 May 2016
DOI:10.1039/C6CC90215D
Correction for ‘Discovery of a 19F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells’ by Qiuyan Shi et al., Chem. Commun., 2016, 52, 5136–5139.
Co-reporter:Zihong Wan, Yu Li, Shaowei Bo, Ming Gao, Xuemeng Wang, Kai Zeng, Xin Tao, Xuefei Li, Zhigang Yang and Zhong-Xing Jiang
Organic & Biomolecular Chemistry 2016 vol. 14(Issue 33) pp:7912-7919
Publication Date(Web):20 Jul 2016
DOI:10.1039/C6OB01286H
Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model.
Co-reporter:Long Chen, Haotian Xing, Huaibin Zhang, Zhong-Xing Jiang and Zhigang Yang
Organic & Biomolecular Chemistry 2016 vol. 14(Issue 31) pp:7463-7467
Publication Date(Web):21 Jul 2016
DOI:10.1039/C6OB01352J
A highly practical copper-catalyzed intermolecular chloroazidation of α,β-unsaturated amides has been described, giving a series of azidochlorides in good-to-excellent yields. The stable azidoiodine(III) reagent and SOCl2 were used as azide and chlorine sources, respectively. The synthetic applications of this protocol were also explored by a variety of synthetically useful transformations.
Co-reporter:Yu Li, Guiquan Xia, Qi Guo, Li Wu, Shizhen Chen, Zhigang Yang, Wei Wang, Zhong-Yin Zhang, Xin Zhou and Zhong-Xing Jiang
MedChemComm 2016 vol. 7(Issue 8) pp:1672-1680
Publication Date(Web):20 Jun 2016
DOI:10.1039/C6MD00277C
Fluorine is a highly attractive element for both medicinal chemistry and imaging technologies. To facilitate protein tyrosine phosphatase (PTP)-targeted drug discovery and imaging-guided PTP research on fluorine, several highly potent and 19F MR sensitive PTP inhibitors were discovered through a structure-based focused library strategy.
Co-reporter:Xuefei Li, Zhang Feng, Zhong-Xing Jiang, and Xingang Zhang
Organic Letters 2015 Volume 17(Issue 22) pp:5570-5573
Publication Date(Web):October 29, 2015
DOI:10.1021/acs.orglett.5b02716
A mild and efficient nickel-catalyzed reductive cross-coupling between fluorinated secondary alkyl bromides and (hetero)aryl iodides is described. The use of FeBr2 as an additive successfully overcomes the hydrodebromination and β-fluorine elimination of fluorinated substrates and allows the efficient synthesis of a wide range of trifluoromethyl and difluoroalkyl containing aliphatic compounds with a fluoroalkyl substituted tertiary carbon center. The notable features of this protocol are the synthetic and operational simplicity without preparation of moisture sensitive organometallic reagents and excellent functional group compatibility, even toward active proton containing substrates.
Co-reporter:Guiquan Xia, Yu Li, Zhigang Yang, and Zhong-Xing Jiang
Organic Process Research & Development 2015 Volume 19(Issue 11) pp:1769-1773
Publication Date(Web):October 5, 2015
DOI:10.1021/acs.oprd.5b00270
We have developed a process for the efficient and scalable preparation of heterofunctionalized dodecaethylene glycol from the readily available tetraethylene glycol and its macrocyclic sulfate. By employing the benzyl group as both a protecting group and a separative tag, multiple chromatographic separations were avoided. With this method, α-amino-ω-methyl-dodecaethylene glycol was prepared on a 53 g scale with high purity and 61% overall yield in eight steps and one chromatographic separation.
Co-reporter:Yu Li, Xiaolong Qiu, and Zhong-Xing Jiang
Organic Process Research & Development 2015 Volume 19(Issue 7) pp:800-805
Publication Date(Web):June 12, 2015
DOI:10.1021/acs.oprd.5b00142
Even after decades of effort, the efficient synthesis of the structurally simple but highly valuable molecules monodisperse poly(ethylene glycol)s (M-PEGs) remains a long-standing challenge. In this contribution, we give a brief review of the macrocyclic-sulfate-based strategy developed in our lab for the synthesis of M-PEGs and their monofunctionalized derivatives with a focus on the synthetic efficacy and versatility.
Co-reporter:Hua Zhang;Xuefei Li;Qiuyan Shi;Yu Li;Guiquan Xia;Long Chen; Zhigang Yang ; Zhong-Xing Jiang
Angewandte Chemie 2015 Volume 127( Issue 12) pp:3834-3838
Publication Date(Web):
DOI:10.1002/ange.201410309
Abstract
A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs.
Co-reporter:Hua Zhang;Xuefei Li;Qiuyan Shi;Yu Li;Guiquan Xia;Long Chen; Zhigang Yang ; Zhong-Xing Jiang
Angewandte Chemie International Edition 2015 Volume 54( Issue 12) pp:3763-3767
Publication Date(Web):
DOI:10.1002/anie.201410309
Abstract
A macrocyclic sulfate (MCS)-based approach to monodisperse poly(ethylene glycols) (M-PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62-membered macrocycle) as versatile precursors for a range of monofunctionalized M-PEGs. Through iterative nucleophilic ring-opening reactions of MCS without performing group protection and activation, a series of M-PEGs, including the unprecedented 64-mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M-PEGs.
Co-reporter:Shaowei Bo, Cong Song, Yu Li, Weijiang Yu, Shizhen Chen, Xin Zhou, Zhigang Yang, Xing Zheng, and Zhong-Xing Jiang
The Journal of Organic Chemistry 2015 Volume 80(Issue 12) pp:6360-6366
Publication Date(Web):May 27, 2015
DOI:10.1021/acs.joc.5b00810
Both 19F MRI and optical imaging are powerful noninvasive molecular imaging modalities in biomedical applications. To integrate these two complementary imaging modalities, the design and synthesis of a novel 19F MRI/fluorescence dual-modal imaging agent is reported herein. Through Sonogashira coupling reaction between the fluorinated phenylacetylene and 1,2,4,5-tetraiodobenzene, a fluorophore with 48 symmetrical fluorines at its periphery was constructed with high efficacy. High aqueous solubility was achieved by PEGylation of the fluorophore with monodisperse PEGs. However, an unexpected self-assembly of the PEGylated amphiphilic fluorophore in water “turned off” the 19F NMR signal. However, hydrogenation of the triple bonds or introduction of branched monodisperse PEGs was able to efficiently tune the self-assembly, resulting in the “turning on” of the 19F NMR signal. One of these amphiphiles combines the advantages of label-free fluorescence, high 19F MRI sensitivity, biocompatibility, and excellent aqueous solubility. The results demonstrate the great potential of such amphiphiles for real-time 19F MRI and fluorescence dual-modality imaging.
Co-reporter:Weijiang Yu, Yuqi Yang, Shaowei Bo, Yu Li, Shizhen Chen, Zhigang Yang, Xing Zheng, Zhong-Xing Jiang, and Xin Zhou
The Journal of Organic Chemistry 2015 Volume 80(Issue 9) pp:4443-4449
Publication Date(Web):April 7, 2015
DOI:10.1021/acs.joc.5b00294
To achieve high sensitivity for 19F MRI, a class of novel dendritic molecules with multiple pseudosymmetrical fluorines was designed and efficiently synthesized. Through iterative bromination and Williamson ether synthesis under mild conditions, a fluorinated dendrimer with 540 pseudosymmetrical fluorines was conveniently prepared without performing the group protection in a convergent way. The dendrimer is characterized by a strong 19F NMR peak and short relaxation times. Eventually, an appreciably enhanced 19F MRI at an extremely low concentration (18.5 μM) was achieved, which demonstrated the potential utility of such dendritic molecules in highly sensitive 19F MRI.
Co-reporter:Guiquan Xia, Yuqi Li, Yu Li, Xuefei Li, Hua Zhang, Yihua Bruce Yu, Zhong-Xing Jiang
Journal of Fluorine Chemistry 2014 Volume 165() pp:39-42
Publication Date(Web):September 2014
DOI:10.1016/j.jfluchem.2014.06.005
•The elution order of the analytes corresponds to their eluent-philicity.•Optimal separation was achieved through hetero-pairing of column and eluent.•Separation is further improved by elevated temperature.•Separation in fluorous mixture synthesis is based on the fluorine content percentage F% rather than the number of fluorine atoms.Using the set of fluorinated amphiles that contain the same fluorocarbon moiety but differ in their fluorine content percentage F% (25–45%), the optimal condition for a F%-based separation of these analytes using reverse-phase chromatography was explored. It is found that optimal separation can be achieved by pairing a regular reverse-phase column (such as C8) with a fluorinated eluent (such as trifluoroethanol). Separation is further improved at higher chromatographic temperature with baseline separation achieved at 45 °C. This result indicates that the separation of fluorocarbon-tagged molecules can be based on the fluorine content percentage rather than the number of fluorine atoms.Optimal separation of fluorinated amphiles with HPLC can be achieved by pairing a regular reverse-phase column with a fluorinated eluent and separation is further improved by elevated temperature.
Co-reporter:Yu Li, Qi Guo, Xuefei Li, Hua Zhang, Fanghua Yu, Weijiang Yu, Guiquan Xia, Mingyang Fu, Zhigang Yang, Zhong-Xing Jiang
Tetrahedron Letters 2014 Volume 55(Issue 13) pp:2110-2113
Publication Date(Web):26 March 2014
DOI:10.1016/j.tetlet.2014.02.047
Mono-dispersed poly(ethylene glycols) (PEGs) are of great value in the development of biopharmaceuticals. However, tedious synthesis limits the availability of mono-dispersed PEGs. To address this issue, a fluorous synthesis of mono-dispersed PEGs, discretely PEGylated surfactants and 19F magnetic resonance imaging (MRI) agents has been developed. During the synthesis, both fluorous and normal phase silica gel-based solid-phase extractions were successfully employed to simplify the purifications. This synthesis provided an easy access to valuable mono-dispersed PEGs and related molecules for biomedical application on multi-gram scales.
Co-reporter:Yu Li, Bijaya Thapa, Hua Zhang, Xuefei Li, Fanghua Yu, Eun-Kee Jeong, Zhigang Yang, Zhong-Xing Jiang
Tetrahedron 2013 69(46) pp: 9586-9590
Publication Date(Web):
DOI:10.1016/j.tet.2013.09.040
Co-reporter:Mingyang Fu; Long Chen; Yongpeng Jiang; Zhong-Xing Jiang;Zhigang Yang
Organic Letters () pp:
Publication Date(Web):January 11, 2016
DOI:10.1021/acs.orglett.5b03080
A highly practical copper-catalyzed intermolecular halotrifluoromethylation of alkenes has been developed under mild reaction conditions. A variety of Cl/Br-containing trifluoromethyl derivatives were directly synthesized from a wide range of alkenes, including electron-deficient and unactivated alkenes.
Co-reporter:Long Chen, Haotian Xing, Huaibin Zhang, Zhong-Xing Jiang and Zhigang Yang
Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 31) pp:NaN7467-7467
Publication Date(Web):2016/07/21
DOI:10.1039/C6OB01352J
A highly practical copper-catalyzed intermolecular chloroazidation of α,β-unsaturated amides has been described, giving a series of azidochlorides in good-to-excellent yields. The stable azidoiodine(III) reagent and SOCl2 were used as azide and chlorine sources, respectively. The synthetic applications of this protocol were also explored by a variety of synthetically useful transformations.
Co-reporter:Qiuyan Shi, Yu Li, Shaowei Bo, Xiaofei Li, Peng Zhao, Qi Liu, Zhigang Yang, Hengjiang Cong, Hexiang Deng, Mingnan Chen, Shizhen Chen, Xin Zhou, Hong Ding and Zhong-Xing Jiang
Chemical Communications 2016 - vol. 52(Issue 29) pp:NaN5139-5139
Publication Date(Web):2016/03/10
DOI:10.1039/C6CC01508E
Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and 19F MRI sensitivity was discovered as a novel theranostic agent.
Co-reporter:Zihong Wan, Yu Li, Shaowei Bo, Ming Gao, Xuemeng Wang, Kai Zeng, Xin Tao, Xuefei Li, Zhigang Yang and Zhong-Xing Jiang
Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 33) pp:NaN7919-7919
Publication Date(Web):2016/07/20
DOI:10.1039/C6OB01286H
Although monodisperse polyethylene glycols (M-PEGs) above 4000 Da are especially valuable in biomedical applications, their synthesis remains a long-standing challenge. To this end, a peptide-based strategy for such M-PEGs was developed. With macrocyclic sulfates as the key intermediates, a panel of oligoethylene glycol (OEG) containing ω-amino acids were prepared with high efficiency. Through solid phase peptide synthesis (SPPS), these amino acids were conveniently assembled into a series of amide bond-containing M-PEGs with high flexibility in molecular weight and amide density selection. With this strategy, an M-PEG of 10262 Da was prepared on a gram scale and its biocompatibility was assessed in a mice model.
Co-reporter:Qiuyan Shi, Yu Li, Shaowei Bo, Xiaofei Li, Peng Zhao, Qi Liu, Zhigang Yang, Hengjiang Cong, Hexiang Deng, Mingnan Chen, Shizhen Chen, Xin Zhou, Hong Ding and Zhong-Xing Jiang
Chemical Communications 2016 - vol. 52(Issue 45) pp:NaN7314-7314
Publication Date(Web):2016/05/18
DOI:10.1039/C6CC90215D
Correction for ‘Discovery of a 19F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells’ by Qiuyan Shi et al., Chem. Commun., 2016, 52, 5136–5139.
Co-reporter:Qiaoli Peng, Yaping Yuan, Huaibin Zhang, Shaowei Bo, Yu Li, Shizhen Chen, Zhigang Yang, Xin Zhou and Zhong-Xing Jiang
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 30) pp:NaN6446-6446
Publication Date(Web):2017/07/14
DOI:10.1039/C7OB01068K
For detecting metal ions with 19F chemical exchange saturation transfer magnetic resonance imaging (19F CEST MRI), a class of novel fluorinated chelators with diverse fluorine contents and chelation properties were conveniently synthesized on gram scales. Among them, a DTPA-derived chelator with high sensitivity and selectivity was identified as a novel 19F CEST imaging probe for simultaneously detecting multiple metal ions.
![1-Propyne, 3-[2,2,2-trifluoro-1,1-bis(trifluoromethyl)ethoxy]-](/data/chemimg/3723400/1632977-59-3.png)
![1-Propyne, 3-[2,2,2-trifluoro-1,1-bis(trifluoromethyl)ethoxy]-](/data/chemimg/3723400/1632977-59-3_b.png)
![[4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)phenyl]methanol](http://img.cochemist.com/ccimg/356100/356055-77-1.png)
![[4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluorodecyl)phenyl]methanol](http://img.cochemist.com/ccimg/356100/356055-77-1_b.png)
![Ethanol, 2-[2-[2-(triphenylmethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/133700/133699-09-9.png)
![Ethanol, 2-[2-[2-(triphenylmethoxy)ethoxy]ethoxy]-](http://img.cochemist.com/ccimg/133700/133699-09-9_b.png)
![Ethanol, 2-[2-(triphenylmethoxy)ethoxy]-](http://img.cochemist.com/ccimg/105600/105589-77-3.png)
![Ethanol, 2-[2-(triphenylmethoxy)ethoxy]-](http://img.cochemist.com/ccimg/105600/105589-77-3_b.png)
![Ethanol, 2-[2-(2-azidoethoxy)ethoxy]-](/data/chemimg/964400/86520-52-7.png)
![Ethanol, 2-[2-(2-azidoethoxy)ethoxy]-](/data/chemimg/964400/86520-52-7_b.png)
![1-PROPANOL, 3,3'-[1,3-PROPANEDIYLBIS(THIO)]BIS-](http://img.cochemist.com/ccimg/56000/55982-70-2.png)
![1-PROPANOL, 3,3'-[1,3-PROPANEDIYLBIS(THIO)]BIS-](http://img.cochemist.com/ccimg/56000/55982-70-2_b.png)
![Ethanol, 2,2'-[1,4-butanediylbis(oxy)]bis-](http://img.cochemist.com/ccimg/21200/21159-68-2.png)
![Ethanol, 2,2'-[1,4-butanediylbis(oxy)]bis-](http://img.cochemist.com/ccimg/21200/21159-68-2_b.png)
![Ethanol, 2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-](/data/chemimg/976600/86770-67-4.png)
![Ethanol, 2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]-](/data/chemimg/976600/86770-67-4_b.png)
