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陈悦

姓名:陈悦


2016年国家杰出青年科学基金获得者,天津市“131” 创新型人才培养工程第一层次,教育部新世纪优秀人才支持计划,霍英东教育基金会高等院校青年教师基金应用研究课题资助获得者,南开大学“百名青年学术带头人”,天津市创新人才推进计划重点领域创新团队负责人。

职称:教授

学科方向:药物化学,天然产物合成

招生方向:药物化学

课题组成员

副教授:张泉博士、卢亚欣博士、李静博士

讲师:王良博士、丁亚辉博士

博士后:郝鑫博士、王达博士、李亮博士、张梦裔博士

联系地址:天津市津南区海河教育园区同砚路38号南开大学综合实验楼C524

电话:022-85358387

电子邮箱:yuechen@nankai.edu.cn

教育背景与工作经历:

陈悦,1973 年生,教授,博士生导师。1994年毕业于湖南师范大学化学系,1997 年7 月获得中国科学院上海有机化学研究所硕士学位,2003年5月获University of Notre Dame博士学位,同年加入美国Kosan Biosciences,担任Scientist I和Scientist II,期间研发多个抗癌药物进入临床试验。

陈悦教授2007年回国加入南开大学药学院。近年来在药物化学领域发表多篇论文(包括J. Am. Chem. Soc., Angew. Chem. Int. Ed., J. Med. Chem., Org. Lett.);12项发明专利已获授权,其中1项专利获欧美等20国家的授权。

陈悦教授为研究生讲授“高等有机合成”课程。

研究方向:靶向癌症干细胞的药物化学

大约90%的癌症死因,源于癌症的复发和转移。越来越多的科学研究发现:癌症干细胞在很多癌症的产生、发展、复发、耐药和转移过程中扮演重要角色。目前临床使用的药物治疗与放疗手段,均只针对普通癌细胞,而不能选择性杀灭癌症干细胞。癌症干细胞在各种手段治疗以后,往往能够存活下来,引起癌症的复发和转移。但是,目前还很难发现靶向癌症干细胞的化合物;而已经确认靶向癌症干细胞的化合物,无论在种类和数量上,均非常有限。

研究课题:抗脑胶质母细胞瘤新药ACT001与酯肽类化合物

在抗癌症干细胞天然产物的骨架基础上,课题组通过合理的设计、全合成与半合成的手段,发现了多个系列的靶向癌症干细胞的化合物。目前,第一代候选药物DMAMCL(即ACT001)具有抗白血病干细胞作用,并可以穿过血脑屏障,现已作为抗脑胶质母细胞瘤1.1类新药先后进入澳洲和国内I期临床试验,部分临床I期结果公布于美国ASCO会议,结论为: “At well-tolerated doses, ACT001 showed satisfactory bioavailability and preliminary evidence of anti-tumor activity in a subset of patients”ACT001同时获美国FDA和欧盟EMA“孤儿药”资格认定。通过自主研发获得欧美孤儿药资格认证,系天津首例,全国罕见。最近,澳洲开展了治疗儿童实体瘤的临床I期试验,天津肿瘤医院也开展了国内治疗成人胶质瘤的临床I期试验。

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                             图1. 美国ASCO会议公布部分ACT001临床I期结果


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                            图2. ACT001获美国和欧盟“孤儿药”资格认定

陈悦教授完成了具有抗癌症干细胞的酯肽类化合物rakicidin A、vinylamycin及BE-43547A2全合成,并确定了其绝对立体构型,开辟了抗癌症干细胞药物化学新领域。其中BE-43547A2具有显著的抗胰腺癌干细胞活性。相关论文发表于化学顶级期刊Angew. Chem,并被该期刊选为热点论文(Hot Paper),并进一步选为新闻发布(Press Release)。并被全球10家科技媒体所转载。

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                                     3. BE-43547化合物的关注度

欢迎加入课题组:可直接联系(王良博士)、(张泉博士)邮箱lwang@nankai.edu.cn;zhangquan@nankai.edu.cn

1. 课题组欢迎硕士生,本科生加入

2. 课题组欢迎博士生,博士后加入

代表性论文:

56. Junhong Xiang; Yahui Ding*; Jiaxin Li; Xiuhe Zhao; Yuanjun Sun; Da Wang; Liang Wang*; Yue Chen*, Ovatodiolides: Scalable Protection-free Syntheses, Configuration Determination and Biological Evaluation against Hepatic Cancer Stem Cells, Angew. Chem. Int. Ed. 2019, online, 10.1002/anie.201904096.

55.   Weizhi Ge, Zhongquan Liu, Yu Sun, Tianpeng Wang, Hongyu Guo, Xinyi Chen, Shengzu Li, Mengmeng Wang, Yue Chen*, Yahui Ding*, Quan Zhang*, Design and synthesis of parthenolide- SAHA hybrids for intervention of drugresistant acute myeloid leukemia, Bioorg. Chem. 2019, 87, 699–713.

54. Yuanjun Sun, Ruifei Zhou, Honglei Xu, Xiuwen Su, Dehong Wang, Chao Wang, Yahui Ding, Liang Wang*, Yue Chen* Syntheses and biological evaluation of BE-43547A2 analogues modified at O35 ester and C15-OH sites. Tetrahedron 2019, 75, 1808-1818. (Invited Paper, Special Issue, In Meomory of Weishan Zhou).

53.   Weizhi Ge, Xin Hao, Fangzhi Han, Zhongquan Liu, Tianpeng Wang, Ning Chen, Yahui Ding*, Yue Chen*, Quan Zhang*. Synthesis and structure-activity relationship studies of parthenolide derivatives as potential anti-triple negative breast cancer agents. Eur. J. Med. Chem., 2019, 166, 445-469.

52.   Weizhi Ge, Xinyi Chen, Fangzhi Han, Zhongquan Liu, Tianpeng Wang, Mengmeng Wang, Yue Chen*, Yahui Ding*, Quan Zhang*. Synthesis of Cucurbitacin B derivatives as potential anti-hepatocellular carcinoma agents. Molecules 2018, 18, 23(12)

51.   Yahui Ding#, Hongyu Guo#, Weizhi Ge#, Xinyi Chen, Shengzu Li, Mengmeng Wang, Yue Chen*, Quan Zhang* Copper(I) Oxide nanoparticles catalyzed click chemistry based synthesis of melampomagnolide B-triazole conjugates and their anti-cancer activities. Eur. J. Med. Chem., 2018, 156, 216-229.

50.   Yunfeng Tian, Yahui Ding, Xiaolong Xu, Yanju Bai, Yang Tang, Xin Hao, Weicheng Zhang*, Yue Chen* Total synthesis and biological evaluation of nannocystin analogues modified at the polyketide phenyl moiety. Tetrahedron Lett. 2018, 59, 3206-3209.

49.   Yuanjun Sun, Xiuwen Su, Ruifei Zhou,Dehong Wang,Yuan Zhao,Yuhang Jiang,Liang Wang*,Yue Chen* Total synthesis of BE-43547A(2). Tetrahedron 2018, 74, 5955-5964.

48.   Baijun Ye, Peng Jiang, Tingrong Zhang, Yuanjun Sun, Xin Hao, Yingjun Cui, Liang Wang*,Yue Chen* Total Synthesis of the Highly N-Methylated Peptides Carmabin A and Dragomabin. Marine Drugs 2018, 16, 338.

47.   Baijun Ye, Peng Jiang, Tingrong Zhang, Yahui Ding, Yuanjun Sun, Xin Hao, Lanshu Li, Liang Wang*, Yue Chen* Total Synthesis of the Highly N-Methylated Peptide Jahanyne J. Org. Chem. 2018, 83, 6741-6747.

46.   Jing Li, Shanshan Li, Jianshuang Guo, Qiuying Li, Jing Long, Cheng Ma, Yahui Ding, Chunli Yan, Liangwei Li, Zhigang Wu, He Zhu, Keqin Li, Liuqing Wen, Quan Zhang, Qingqing Xue, Caili Zhao, Ning Liu, Ivaylo Ivanov, Ming Luo, Rimo Xi, Haibo Long, Peng Wang, * Yue Chen,* Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and Suppresses Leukemia. J. Med. Chem., 2018, 61, 4155-4164. (ACS editor’s choice)

45.   Jian Chen, Jingpei Li, Lingling Wu, Yan Geng, Jianming Yu, Chuanke Chong, Mengmeng Wang, Yuan Gao, Cuigai Bai, Yahui Ding,* Quan Zhang,* Yue Chen,* Synthesis and Anti-pancreatic Cancer Activities of Rakicidin A analogues. Eur. J. Med. Chem., 2018, 151, 601-627.

44.   Yunfeng Tian1, Xiaolong Xu1, Yahui Ding, Xin Hao, Yanju Bai, Yang Tang, Xuemei Zhang, Qiuying Li, Zhantao Yang, Weicheng Zhang,* Yue Chen,* Synthesis and Biological Evaluation of Nannocystin Analogues toward Understanding the Binding Role of the (2R,3S)-Epoxide in Nannocystin A. Eur. J. Med. Chem., 2018, 150, 626-632.

43.   Huiying Li, Dingdi He, Xiujuan Zhao, Tongyan Sun, Quan Zhang, Cuigai Bai,* Yue Chen,* Design and synthesis of novel dasatinib derivatives as inhibitors of leukemia stem cells. Bioorg. Med. Chem. Lett., 2018, 28, 700-706.

42.   Yin Jiang, Huiying Li, Xiaohui Li, Jun Lu, Quan Zhang, Cuigai Bai,* Yue Chen,* Therapeutic Effects of Isothiocyanate Prodrugs on Rheumatoid Arthritis. Bioorg. Med. Chem. Lett., 2018, 28, 737-741.

41.   Yuanjun Sun1, Yahui Ding1,Dongmei Li, Ruifei Zhou, Xiuwen Su, Juan Yang, Xiaoqian Guo, Chuanke Chong, Jinghan Wang, Weicheng Zhang, Cuigai Bai, Liang Wang*, Yue Chen,* Cyclic Depsipeptide BE-43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells. Angew. Chem. Int. Ed., 2017, 56, 14627-14631.

40.   Zhongjin Yang1, Beijia Kuang1, Ning Kang, Yahui Ding, Weizhi Ge, Lihui Lian, Yuan Gao, Yuqing Wei, Yue Chen*, Quan Zhang,* Synthesis and anti-acute myeloid leukemia activity of C-14 modified parthenolide derivatives. Eur. J. Med. Chem., 2017, 127, 296-304.

39.   Jinghan Wang, Beijia Kuang, Xiaoqian Guo, Jianwei Liu, Yahui Ding, Jiangnan Li, Shende Jiang, Ying Liu, Fang Bai, Luyuan Li, Quan Zhang, Xiao-Yu Zhu, Bo Xia, Chun-Qi Li, Liang Wang*, Guang Yang*, Yue Chen,* Total Syntheses and Biological Activities of Vinylamycin Analogs. J. Med. Chem., 2017, 60, 1189-1209.

38.  Zhantao Yang, Xiaolong Xu, Chun-Hua Yang, Yunfeng Tian, Xinyi Chen, Lihui Lian,Wenwei Pan, Xuncheng Su,Weicheng Zhang* and Yue Chen,* Total Synthesis of Nannocystin A. Org. Lett., 2016, 18, 5768–5770.

37.   Zhantao Yang, Meiyan Ma, ChunHua Yang, Yuan Gao, Quan Zhang and Yue Chen,* Determination of the Absolute Configurations of Microtermolide A and B. J. Nat. Prod., 2016, 79, 2408-2412.

36.   Ding Y, Gao H, Zhang Y, Li Y, Vasdev N, Gao Y, Chen Y, Zhang Q,* Alantolactone Selectively Ablates Acute Myeloid Leukemia Stem and Progenitor Cells. Journal of hematology &oncology, 2016, 9, 93.

35.   Ye-Hui Shi, Dong-Fang Dai, Jing Li, Yan-Wei Dong, Yin Jiang, Huan-Gong Li,Yuan Gao, Chuan-Ke Chong, Hui-Ying Li, Xiao-Qian Chu, , Quan Zhang, Zhong-Sheng Tong, Cui-Gai Bai,* and Yue Chen,* Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines. Molecules, 2016, 21, 514.

34.    Feng Sang,# Yahui Ding,# Jinghan Wang,# Bingxia Sun,# Jianlei Sun,# Yan Geng,# Zhang Zhang, Ke Ding, Ling-Ling Wu, Jian-Wei Liu, Cuigai Bai, Guang Yang,* Quan Zhang,* Lu-Yuan Li,* Yue Chen,* Structure?Activity Relationship Study of Rakicidins: Overcoming Chronic Myeloid Leukemia Resistance to Imatinib with 4?Methylester-Rakicidin A. J. Med. Chem., 2016, 59, 1184-1196.

33.    Yong-Tao Li,#Jing-HanWang,#Cheng-Wen Pan, Fan-FeiMeng, Xiao-Qian Chu, Ya-hui Ding, Wen-Zheng Qu, Hui-ying Li,  Quan Zhang, Cui-Gai Bai,* Yue Chen,* Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib. Bioorg. Med. Chem. Lett., 2016, 26, 1419-1427.

32.    Jing Long, Ya-Hui Ding, Pan-Pan Wang, Quan Zhang, Yue Chen,* Total syntheses and structure–activity relationship study of parthenolide analogues. Tetrahedron Lett., 2016, 57, 874–877.

31.    Ya-Hui Ding, Xue Gao, Jing Long, Bei-Jia Kuang, Yue Chen*, Quan Zhang,* Dispirocyclopropyl dehydrocostus lactone selectively inhibits acute myelogenous leukemia cells. Bioorg. Med. Chem. Lett., 2016, 26, 1165-1168.

30.     Zhantao Yang, Guang Yang,* Meiyan Ma, Jiangnan Li, Jianwei Liu, Jinghan Wang, Shende Jiang, Quan Zhang, Yue Chen,* Total Synthesis and Determination of the Absolute Configuration of Vinylamycin. Org. Lett., 2015, 17, 5725-5727.

29.    Zhong-Jin Yang, Wei-Zhi Ge, Qiu-Ying Li, Yaxin Lu, Jian-Miao Gon, Bei-Jia Kuang, Xiaonan Xi, Haiting Wu, Quan Zhang,* Yue Chen,* Syntheses and Biological Evaluation of Costunolide, Parthenolide and Their Fluorinated Analogues. J. Med. Chem.2015, 58, 7007-7020.

28.    Yan Zhao, Sijia Chen, Jiancheng Wang, Hongxin Ni, Qianqian Jia, Xiaowen Chen, Xiaoyan Du, Lu Lu, Bo Huan, Quan Zhang, Yue Chen, Hai-bo Long,* Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF- к B-Dependent Mechanism. Oxidative Medicine and Cellular Longevity, 2015, 1-13.

27.    Feng Sang, Dongmei Li, Xiaolong Sun, Xianqiang Cao, Liang Wang, Jianlei Sun, Bingxia Sun, Lingling Wu, Guang Yang, Xiaoqian Chu, Jinghan Wang, Changming Dong, Yan Geng, Hong Jiang, Haibo Long, Sijia Chen, Guiyan Wang, Shuzhong Zhang, Quan Zhang, Yue Chen,* Total Synthesis and Determination of the Absolute Configuration of Rakicidin A. J. Am. Chem. Soc., 2014, 136, 15787-15791.

26.    Jing Long, Shan-Feng Zhang, Pan-Pan Wang, Xue-Mei Zhang, Zhong-Jin Yang, Quan Zhang*, Yue Chen,*Total syntheses of parthenolide and its analogs with macrocyclic stereocontrol. J. Med. Chem., 2014, 57, 7098-7112.

25.    Ningning Li, Yingtong Xu, Qiang Xian, Cuigai Bai, Taiyi Wang, Lei Wang, Dingdi He, Nannan Xie, Lixin Li, Jiang Wang, Hong-Gang Zhou, Feng Xu, Quan Zhang, Zheng Yin,* Yu Guo,* Yue Chen,* Simplified captopril analogues as NDM-1 inhibitors. Bioorg. Med. Chem. Lett., 2014, 24, 386–389.

24.    Emilie Viennois,* Bo Xiao, iSaravanan Ayyadura, Lixin Wang, Peng G. Wang, Quan Zhang, Yue Chen, Didier Merlin, Micheliolide, A new sesquiterpene lactone that inhibits intestinal inflammation and colitis-associated cancer. Laboratory Investigation, 2014, 94, 950-965.

23.    Xiyan Duan, Yongliang Cui, Yue Chen, Xianglei Kong,* Intramolecular oxo-Diels-Alder rearrangement in collisionally activated dissociation of protonated ions of a mactrocyclic molecule: triazole-epothilone dimer. Journal of Mass Spectrometry, 2014, 49, 755-762.

22.    Can Lu,# Liyan Zhou,# Huijun Xu, Xingyu Chen, Zhongsheng Tong,* Xiaodong Liu, Yong-sheng Jia, Yue Chen, RIP3 overexpression sensitizes human breast cancer cells to parthenolide in vitro via intracellular ROS accumulation. Acta Pharmacologica Sinica, 2014, 35, 929-936.

21.    Jing Long, YaHui Ding, PanPan Wang, Quan Zhang,* Yue Chen,* Protection-group-free semisyntheses of parthenolide and its cyclopropyl analogue. J. Org. Chem., 2013, 78, 10512?10518.

20.    Xiudong Yang, Changming Dong, Jian Chen, Yahui Ding, Qi Liu, Xiaoyan Ma, Quan Zhang, Yue Chen,* Total synthesis of Tubulysin U and its C-4 epimer, Chem. Asian J., 2013, 8, 1213-1222.

19.   Feng Sang, Peng Feng, Jie Chen, Yahui Ding, Xiyan Duan, Jiadai Zhai, Xiaoyan Ma, Bin Zhang, Quan Zhang, Jianping Lin,* Yue Chen,* Epothilone D and its 9-Methyl analogues: Combinatorial syntheses, conformation, and biological activities. Eur. J. Med. Chem.,2013, 68, 321–332.

18.    YaHui Ding, HongXia Fan, Jing Long, Quan Zhang*, Yue Chen,* The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells. Bioorg. Med. Chem. Lett., 2013, 23, 6087–6092.

17.    Jing-Han Wang, Cheng-Wen Pan, Yong-Tao Li, Fan-FeiMeng, Hong-Gang Zhou,  Quan Zhang, Cui-Gai Bai,* Yue Chen,* Safe and highly efficient syntheses of triazole drugs using Cu2O nanoparticle in aqueous solutions. Tetrahedron Lett., 2013, 54, 3406?3409.

16.    Xiudong Yang, Changming Dong, Jian Chen, Qi Liu, Bin Han, Quan Zhang,* Yue Chen,* Design, synthesis, and biological activities of triazoletubulysin V analogue. Tetrahedron Lett., 2013, 54, 2986?2988.

15.    Wei-Wei Ma, Qian-Qian Shi, Ya-Hui Ding, Jing Long, Quan Zhang,* Yue Chen,* Synthesis of micheliolide derivatives and their activities against AML progenitor cells. Molecules, 2013, 18, 5980?5992.

14.    Jian-Cheng Wang, Yan Zhao, Si-Jia Chen, Jing Long, Qian-Qian Jia, Jia-Dai Zhai, Quan Zhang, Yue Chen, Hai-Bo Long, AOPPs induce MCP-1 expression by increasing ROS-mediated activation of the NF-κB pathway in rat mesangialcells: Inhibition by sesquiterpene lactones. Cell. Physiol. Biochem., 2013, 32, 1867–1877.

13.    Qian-Qian Jia, Jian-Cheng Wang, Jing Long, Yan Zhao, Si-Jia Chen, Jia-Dai Zhai, Lian-Bo Wei, Quan Zhang, Yue Chen, Hai-Bo Long, Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells. Molecules, 2013, 18, 13061–13077.

12.    Quan Zhang, Yuhuan Jing, David C. Myles, Yong Li and Yue Chen, Carboalumination-Epoxide Ring Opening for the Formation of 1,4-Disubstituted (Z)-3,6-Alkadienols. Chin. J. Chem. 2013, 31, 773?778.

11.    Quan Zhang, # Yaxin Lu, # Yahui Ding, # Jiadai Zhai, # Qing Ji, # Weiwei Ma, Ming Yang, Hongxia Fan, Jing Long, Bin Han, Wenpeng Zhang, Chuanjiang Qiu, Xiaoyan Ma, Zhongsheng Tong, Yehui Shi, Yongsheng Jia, Qianqian Shi, Haoliang Zhang, Dongmei Li, Jing Zhang, Jianping Lin, Lu-Yuan Li, Yingdai Gao,* Yue Chen,* Guaianolide Sesquiterpene Lactones, a Source to Discover Agents That Selectively Ablate Acute Myelogenous Leukemia Stem and Progenitor Cells. J. Med. Chem., 2012, 55, 8757?8769.

10.    Jia-Dai Zhai, Dongmei, Li, Jing Long, Hao-Liang Zhang, Jian-Ping Lin, Chuan-Jiang Qiu, Quan Zhang,* Yue Chen,* Biomimetic semisynthesis of arglabin from parthenolide, J. Org. Chem.,2012, 77, 7103–7107.

9.    Xiyan Duan, Yan Zhang, Yahui Ding, Jianping Lin, Xianglei Kong, Quan Zhang,

Changming Dong, Guoan Luo,* Yue Chen,* Synthesis of triazole-epothilones by using Cu2O nanoparticles to catalyze 1,3-dipolar cycloaddition. Eur. J. Org. Chem., 2012, 500–508.

8.    Xiyan Duan, Guoan Luo, Yue Chen, Xianglei Kong, Effects of Alkali Metal Ion Cationization on Fragmentation Pathways of Triazole-Epothilone. J. Am. Soc. Mass Spectrom. , 2012, 23, 1126-1134.

7.    Zhenfang Zhang, Changming Dong, Cuihong Yang, Di Hu, Jing Long, Ling Wang, He Li, Yue Chen,* Deling Kong,*Stabilized Copper(I) Oxide Nanoparticles Catalyze Azide-Alkyne Click Reactions in Water. Adv. Synth. Catal., 2010, 352, 1600–1604.

6.    Yaoquan Liu, Yong Li, Yue Chen, Hao Zheng, Mark Claypool, David C. Myles, Christopher W. Carreras, 9-Dihydroerythromycins as non-antibiotic motilin receptor agonists. Bioorg. Med. Chem. Lett., 2010, 20, 5658-5661.

5.    Simon J. Shaw,* Yue Chen, Hao Zheng, Hong Fu, Mark A. Burlingame, Saul Marquez, Yong Li, Mark Claypool, Christopher W. Carreras, William Crumb, Dwight J. Hardy, David C. Myles, Yaoquan Liu, Structure-Activity Relationships of 9-Substituted-9-Dihydroerythromycin-Based Motilin Agonists: Optimizing for Potency and Safety. J. Med. Chem., 2009, 52, 6851-6859.

4.    Richard E. Taylor,* Yue Chen, Gabriel M. Galvin, Praveen K. Pabba, Conformation-activity relationships in polyketide natural products: Towards the biologically active conformation of epothilone. Org. Biomol. Chem., 2004, 2, 127–132.

3.    Richard E. Taylor,* Yue Chen, Alicia Beatty, Conformation-activity relationships in polyketide natural products: a new perspective on the rational design of epothilone analogues. J. Am. Chem. Soc., 2003, 125, 26–27.

2.   Richard E. Taylor,* Yue Chen, Total synthesis of epothilones B and D. Org. Lett., 2001, 3, 2221–2224.

1.   Richard E. Taylor, Gabriel M. Galvin, Kerry A. Hilfiker, and Yue Chen, A Formal Total Synthesis of Epothilone A: Enantioselective Preparation of the C1?C6 and C7?C12 Fragments, J. Org. Chem., 1998, 63, 9580-9583.


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