期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

7-对氟苯甲酰基-喜树碱烷基酯的合成

Synthesis of 7-(p-fluoro)benzoyl-camptothecin alkyl esters
下载PDF
导出
摘要 为降低喜树碱对正常细胞的毒性,提高抗肿瘤活性和溶解性。以20(S)-喜树碱和对氟苯甲醛为起始原料,经Minisci反应和酯化反应得到目标化合物,其结构经MS、1HNMR和IR确证。通过四因素三水平的正交试验优化并确定了Minisci反应的最佳条件:0.5g喜树碱,30mL75%H2SO4,1.5mL对氟苯甲醛,30%H2O2/FeSO4.7H2O物质的量比为20:1,1.0mL30%H2O2,反应温度0～2℃,反应时间6h,收率55.2%。 To enhance the antitumor activity,improve the solubility of natural camptothecin,and reduce its toxicity,7-（p-fluoro）benzoyl-camptothecin was synthesized from p-fluorobenzaldehyde and 20（S）-camptothecin by the Minisci radical displacement reaction.Thus,three 7-（p-fluoro）benzoyl-camptothecin esters were prepared by acylation of 7-（p-fluoro）benzoyl-camptothecin using the corresponding acylating reagents such as organic anhydrides and organic acids.The optimum reaction conditions were obtained as follows：0.5 g of 20（S）-camptothecin,30 mL of 75% H2SO4,1.5 mL of p-fluorobenzaldehyde,n（30% H2O2）∶n（FeSO4·7H2O）=20∶1,1.0 mL of 30% H2O2,a reaction temperature of 0～2 ℃,and a reaction time of 6 h,with the yield reaching 58.2%.The structures of four compounds were confirmed by IR,MS and ^1HNMR.
作者 聂丽娟 严志平 李响敏 邹艳红
机构地区 南昌大学理学院化学系 南昌大学中德联合研究院
出处 《化学试剂》 CAS CSCD 北大核心 2008年第6期405-408,共4页 Chemical Reagents
基金 江西省科技厅攻关项目赣财教[2005]132号
关键词 7-对氟苯甲酰基-20(S)-喜树碱 7-对氟苯甲酰基-20(S)-喜树碱烷基酯 合成 20（S）-7-（p-fluoro）benzoyl-camptothecin 20（S）-7-（p-fluoro）benzoyl-camptothecin alkyl esters synthesis
分类号 TQ243.4 [化学工程—有机化工]
  • 相关文献

参考文献11

  • 1WALL M E, WANI M C,COOK C E,et al. Plant antitumor agents. Ⅰ. the isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminata[J]. J. Am. Chem. Soc., 1966,88 (16) : 3 888-3 890.
  • 2HSIANG Y H, HERTZBERG R, HECHT S, et al. Camptothecin induces protein-linked DNA breaksvia mammalian DNA topoisomerase Ⅰ [J]. J. Biol. Chem., 1985,260 (27) : 14 873-14 878.
  • 3GIOVANELLA B C, STEHLIN J S, WALL M E, et al. DNA topoisomerase Ⅰ-targetedchemotherapy of human colon cancer in xenografts[J]. Science, 1989,246(4 933) : 1 046-1 048.
  • 4DALLAVALLE S, MERLINI L, MORINI G, et al. Synthesis and cytotoxic activity of substituted 7-aryliminomethyl derivatives of camptothecin [J]. Eur. J. Med. Chem., 2004, 39 (6) :507-513.
  • 5DALLAVALLE S, GIANNINI G, ALLOATTI D, et al. Synthesis and cytotoxic activity of polyamine analogues of camptothecin[J]. J. Med. Chem. ,2006,49(17) :5 177-5 186.
  • 6NAKAGAWA-GOTO K, NAKAMURA S, BASTOW K F, et al. Antitumor agents.256, conjugation of paclitaxel with other antimor agents: evaluation of novel conjugates as cytotoxic agents[J]. Bioorg. Med. Chem. Lett. ,2007,17(10):2 894-2 898.
  • 7WANI M C, RONMAN P E, WALL M E. Plant antitumor agents. 18. synthesis and biological activity of camptothecin analogs[J]. J. Med . Chem. ,1980,23(5) :554-560.
  • 8HERTZBERG R, BUSBY R W, CARANFA M J, et al. Irreversible trapping of the DNA-topoisomerase Ⅰ covalent complex affinity labeling of the camptothecin binding site[J]. J. Biol. Chem. , 1990,265(31):19 287-19 295.
  • 9CAO Z S, HARRIS N, KOZIELSKI A, et al. Alkyl esters of camptothecin and 9-nitrocamptothecln: synthesis, in vitro pharmacokinetics, toxicity, and antitumor activity [J]. J. Med. Chem., 1998,41(1) :31-37.
  • 10HENNE W A, DOORNEWEERD D D, HILGENBRINK A R, et al. Synthesis and activity of a folate peptide camptothecin prodrug [J]. Bioorg. Med. Chem. Lett., 2006, 16 (2.0) :5 350-5 355.

二级参考文献16

  • 1[1]WALL M E, WANI M C, PALMER K H, et al.Plant antitumor agents. I. the isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from camptotheca acuminata [J]. J of American Chemical Society, 1966, 88(16):3888-3890.
  • 2[2]MUGGIA F M. Twenty Years Later: Review of Clinical Trials with Camptothecin Sodium. In Camptothecins: New Anticancer Agents [M]. Boca Raton:CRC Press, 1995. 43-50.
  • 3[3]BURRIS H A, FIELDS S M, KUHU J G, et al.Camptothecins: Dose-limiting Toxicities and Their Management. In Camptothecins: New Anticancer Agents[M]. Boca Raton: CRC Press, 1995. 113-121.
  • 4[4]HSIANG Y H, HERTZBERG R P, HECHT S, et al.Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I[J]. J of Biological Chemistry, 1985, 260(27): 14873-14878.
  • 5[5]WANI M C, NICHOLAS A W, WALL M E. Plant antitumor agents. 23. synthesis and antileukemic activity of camptothecin analogues [J]. J of Medicinal Chemistry, 1986, 29(8): 1553-1555.
  • 6[6]WALL M E, WANI M C, NICHOLAS A W , et al.Plant antitumor agents. 30. synthesis and structure-activity of novel camptothecin analogues [J]. J of Medicinal Chemistry, 1993, 36(18): 2689-2700.
  • 7[7]WANI M C, WANI M E. Plant antitumor agents. Ⅱ.structure of two new alkaloids from camptothecin acuminata[J]. J of Organic Chemistry, 1969, 34(5):1364-1367.
  • 8[8]KINGSBURG W D, BOEHM J C, JAKAS D R, et al.Synthesis of water-soluble (aminoalkyl) camptothecin analogues: inhibition of topoisomerase I and antitumor activity[J]. J of Medicinal Chemistry, 1991, 34(1): 98-107.
  • 9[9]SAWADA S, MATSUOKA S, NOKATA K, et al.Synthesis and antitumor activity of 20 (S)-camptothecin derivatives: a-ring Modified and 7,10-disubstituted camptothecins[J]. Chemical and Pharmaceutical Bulletin, 1991, 39(12): 3183-3188.
  • 10[10]ROWINSKY EK, JOHNSONTR, GEYERCE, et al. DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies [J]. J of Clinical Oncology, 2000, 18 (17):3151-3163.

共引文献2

化学试剂
2008年 第6期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部