喜树碱衍生物的合成及其抗肿瘤活性的研究
摘要
喜树碱是从珙桐科植物喜树等植物中提取的具有抗癌活性的生物碱。喜树碱及其衍生物是高效的拓扑异构酶Ⅰ的抑制剂。其抗肿瘤机理是通过稳定拓扑异构酶Ⅰ-DNA的复合物,影响DNA的复制来实现的。近几十年来,人们合成成千上万的喜树碱衍生物并对其生物活性进行测试,已经发展了三个喜树碱衍生物的抗肿瘤药(Irinotecan,Topotecan和Belotecan),另有数十个衍生物正处于临床或临床前实验。本论文在前人研究得到的喜树碱结构活性关系以及反应性的基础上,对喜树碱进行结构修饰,获得了3类新的喜树碱衍生物,并对合成的衍生物进行体内体外抗肿瘤活性研究。
1.7-位环烷基喜树碱衍生物的合成及抗肿瘤活性研究
喜树碱7-位取代基特别是亲脂性基团在血液中具有独特的性质,它们能阻止喜树碱E环体内水解产生的开环羧酸盐与人血清蛋白(HSA)的结合,提高内酯环的体内稳定性,进而提高活性,降低毒性。喜树碱7-位取代基主要是通过自由基取代引入的。我们将溴代烷烃的自由基烷基化反应应用到7-烷基取代的喜树碱衍生物的合成,发展了一条新的合成路线。该路线原料价廉易得,产率中等,在合成7-环烷基喜树碱系列化合物时与现有的方法(Sawada方法)相当甚至更好。利用该路线,我们成功合成了一系列的7-环烷基-10-取代的喜树碱衍生物。初步的体外细胞毒性实验结果表明该系列的衍生物具有非常高的抗肿瘤活性,最高的比Topotecan高出40倍。其结构与活性关系与我们之前的定量计算相一致,即7-取代基的亲脂性越大,其生物活性越高。但7-环辛基喜树碱的情况出现例外,其活性反而比亲脂性较小的小环取代的喜树碱衍生物低。我们推测可能与环辛基的空间位阻有关。
2.E环开环衍生物的合成及其生物活性评价
完整的E环一度被认为是保持喜树碱活性的重要因素。然而调查发现喜树碱E环开环的“羟基-酰胺”化合物或“酯-酰胺”化合物具有与喜树碱相当的活性。我们首次引入了吗啉、咪唑等碱基,用简单的方法合成了两类10个E环开环衍生物,并通过初步的体外细胞抑制测试各筛选一个“羟基-酰胺”和“酯-酰胺”衍生物进行小鼠和裸鼠移植瘤的抑制研究。结果表明含有吗啉基的衍生物的活性比含咪唑基的活性高,而丙酯比乙酯对活性更有利。含吗啉基团的“羟基-酰胺”化合物3-5a不仅具有比对照药物喜树碱、SN-38以及Topotecan更高的体外活性,而且有效抑制多种裸鼠的移植瘤的生长,毒性小。7/10位的取代基有利于提高这类开环衍生物的活性。结果表明喜树碱“羟基-酰胺”化合物并非仅仅是喜树碱的“前药”,而自身是有比喜树碱更优的生物特性。
3.E环五元环内酯衍生物的合成及其生物活性评价
高喜树碱(hCPT)及其他数类具有活性的E环修饰过的喜树碱类似物的发现,改变了人们对喜树碱E环作用的看法。这激励我们设计合成了一类新的喜树碱E环修饰的化合物——γ-酰胺五元环内酯类似物,其合成包括一个关键的三步串联反应:喜树碱内酯经胺解开环得“羟基-酰胺”,然后在PDC-CH_2Cl_2条件下直接获得目标化合物。端基三级胺因为氧化条件可能也会氧化三级胺不能按上述策略引入。经过探索,我们通过片断拼接的方式经中间体醛基的还原胺化引入,增加其水溶性。本部分共合成了包括7/10位取代的E环γ-酰胺五元环内酯喜树碱类似物50几个,其中的21个化合物进行体外生物活性测试。可惜这个系列化合物的生物活性与喜树碱及阳性对照药物相比下降了很多,最好的也只与Topotecan相当。分析这类化合物活性低的原因,可能跟新生成的17-位羰基会与D环的羰基发生竞争配位有关。7/10位的取代基在这个系列的化合物中表现出了两种不同的结构活性关系:当酰胺N上的取代基是正丁基时,7/10位的取代基对化合物的抗癌活性有利;然而当酰胺N上的取代基含有三级胺的时候,7/10位的取代基对活性反而不利。
此外,我们还探索了7-氨基取代的喜树碱衍生物的合成,发现通过氨基自由基反应不能直接在喜树碱7-位接上引入氨基,并提出了可能的解释。
Camptothecin(CPT) is a natural antitumor alkaloid isolated from Chinese tree Camptotheca acuminate.CPT and many of its derivatives are potent inhibitor of Topoisomerase I(Topo I).Their antitumor mechanism is that CPT and its derivatives could stabilize the Topo I-DNA complex and subsequently influence the republication of DNA and cause the cell death.During the last several decades, thousands of CPT derivatives were synthesized and their antitumor activities were evaluated.Three of the analogues Irinotecan,Topotecan and Belotecan have been approved as chemotherapeutic drugs used in clinic treatment on human cancers,and several other derivatives are now in different phases of clinic and pre-clinic trials. Base on the research on the structure-activity relationship(SAR) and reactive properties of CPT from literature,we have designed and synthesized 3 series of novel CPT analogues,and evaluated their antitumor activities to find promising new drugs.
1.Synthesis and biological evaluation of 7-cycloalkylcamptothecin derivatives
Substitutions especially lipophilic groups at 7-position of CPT have instinct properties for activity in human blood.They could stop the interaction of carboxylate form of CPT E-ring with human serum albumin(HSA),and as a result,stabilize the E-ring lactone,enhance the biological activities and reduce the side effects. Substitutions are generally attached to 7-position via radical reactions.We applied the radical alkylation of alkylbromide to synthesize 7-alkylcamptothecin derivatives and developed a novel route for preparation 7-alkylcamptothecin derivatives.With this new method,we used much cheaper and more facile starting materials to get comparable or even higher yield than the methods reported in preparing 7-cycloalkylcamptothecin analogues.The result of antitumor activities demonstrated that the synthetic compounds of 7-cycloalkylcamptothecin derivatives have high activity which even up to 40 times higher than reference drug Topotecan.The SAR matched the conclusion we achieved before with QSAR study.The exceptional compound 7-cyclooctyl camptothecin showed low activity,which might imply a different model of combination with biological macromolecular due to its steric bulks.
2.Synthesis and biological evaluation of E-ring opened camptothecin derivatives
An intact lactone E-ring was once considered to be indispensable for CPT's activity.However,recent investigations indicated that CPT E-ring opened derivatives "hydroxyl-amide" and "ester-amid" compounds have comparable activity with CPT itself.We firstly introduced morpholine and imidazole groups to CPT "hydroxyl-amide" and "ester-amid" derivatives with simple procedures,and prepared 10 E-ring opened CPT analogues.Biological evaluation in vitro presented that activities of "hydroxyl-amide" compounds with morpholine group were high than that with imidazole group,and in "ester-amid" compounds,propionate derivatives have higher activities than acetate analogues.7/10 substitutions enhance the activitiy of the E-ring opened derivatives.The inhibition of "hydroxyl-amide" 3-5a on transplanted human tumors in mice and nude mice showed higher efficacy than reference drugs.The biological evaluation implied that CPT "hydroxyl-amide" compounds have their intrinsic antitumor property,not just play as the pre-drug of its ring-closed parent CPT.
3.Synthesis and biological evaluation of E-ring five-membered lactone analogues of CPT
The high activities of homo-camptothecin and several E-ring modified CPT analogues change the opinions of the function of CPT E-ring.We designed and synthesized a series of E-ringγ-amide five-membered lactone analogues of CPT and evaluated their biological activity.The preparation of this series of compounds underwent a key procedure with three-step-tandem reaction.This domino reaction occurred on the PDC-CH_2Cl_2 condition after CPTs were opened by amines,and formed the target compounds.Derivatives bearing with terminal tertiary amines could not be achieved by the same strategy since tertiary amines were also oxidated by PDC.After different sequences were explored,the best strategy is connecting subsection to introduce tertiary amines.We gained more than 50γ-amide lactone analogues,including 7/10 substituted compounds,and 21 of them were tested to evaluate their activity.Disappointing,this E-ring modified CPT analogues presented low antitumor activity.Only one of them displayed comparable activity with reference drug Topotecan.Presumably,the 17-carbonyl in these compounds might compete with carbonyl in the D-ring in binding to biological macromolecular and caused the reduced activity.7/10 substitutions revealed two different contribution to the activity from SAR study,when butyl substituted at the N-amide,they favored the antitumor activity,but when the amide were substituted with tertiary amines,they disfavored the activities.
In addition,amine radical reaction was employed for exploring the pathway to prepare 7-N substituted CPT analogues,though failed.The possible explanation was presented.
1.7-位环烷基喜树碱衍生物的合成及抗肿瘤活性研究
喜树碱7-位取代基特别是亲脂性基团在血液中具有独特的性质,它们能阻止喜树碱E环体内水解产生的开环羧酸盐与人血清蛋白(HSA)的结合,提高内酯环的体内稳定性,进而提高活性,降低毒性。喜树碱7-位取代基主要是通过自由基取代引入的。我们将溴代烷烃的自由基烷基化反应应用到7-烷基取代的喜树碱衍生物的合成,发展了一条新的合成路线。该路线原料价廉易得,产率中等,在合成7-环烷基喜树碱系列化合物时与现有的方法(Sawada方法)相当甚至更好。利用该路线,我们成功合成了一系列的7-环烷基-10-取代的喜树碱衍生物。初步的体外细胞毒性实验结果表明该系列的衍生物具有非常高的抗肿瘤活性,最高的比Topotecan高出40倍。其结构与活性关系与我们之前的定量计算相一致,即7-取代基的亲脂性越大,其生物活性越高。但7-环辛基喜树碱的情况出现例外,其活性反而比亲脂性较小的小环取代的喜树碱衍生物低。我们推测可能与环辛基的空间位阻有关。
2.E环开环衍生物的合成及其生物活性评价
完整的E环一度被认为是保持喜树碱活性的重要因素。然而调查发现喜树碱E环开环的“羟基-酰胺”化合物或“酯-酰胺”化合物具有与喜树碱相当的活性。我们首次引入了吗啉、咪唑等碱基,用简单的方法合成了两类10个E环开环衍生物,并通过初步的体外细胞抑制测试各筛选一个“羟基-酰胺”和“酯-酰胺”衍生物进行小鼠和裸鼠移植瘤的抑制研究。结果表明含有吗啉基的衍生物的活性比含咪唑基的活性高,而丙酯比乙酯对活性更有利。含吗啉基团的“羟基-酰胺”化合物3-5a不仅具有比对照药物喜树碱、SN-38以及Topotecan更高的体外活性,而且有效抑制多种裸鼠的移植瘤的生长,毒性小。7/10位的取代基有利于提高这类开环衍生物的活性。结果表明喜树碱“羟基-酰胺”化合物并非仅仅是喜树碱的“前药”,而自身是有比喜树碱更优的生物特性。
3.E环五元环内酯衍生物的合成及其生物活性评价
高喜树碱(hCPT)及其他数类具有活性的E环修饰过的喜树碱类似物的发现,改变了人们对喜树碱E环作用的看法。这激励我们设计合成了一类新的喜树碱E环修饰的化合物——γ-酰胺五元环内酯类似物,其合成包括一个关键的三步串联反应:喜树碱内酯经胺解开环得“羟基-酰胺”,然后在PDC-CH_2Cl_2条件下直接获得目标化合物。端基三级胺因为氧化条件可能也会氧化三级胺不能按上述策略引入。经过探索,我们通过片断拼接的方式经中间体醛基的还原胺化引入,增加其水溶性。本部分共合成了包括7/10位取代的E环γ-酰胺五元环内酯喜树碱类似物50几个,其中的21个化合物进行体外生物活性测试。可惜这个系列化合物的生物活性与喜树碱及阳性对照药物相比下降了很多,最好的也只与Topotecan相当。分析这类化合物活性低的原因,可能跟新生成的17-位羰基会与D环的羰基发生竞争配位有关。7/10位的取代基在这个系列的化合物中表现出了两种不同的结构活性关系:当酰胺N上的取代基是正丁基时,7/10位的取代基对化合物的抗癌活性有利;然而当酰胺N上的取代基含有三级胺的时候,7/10位的取代基对活性反而不利。
此外,我们还探索了7-氨基取代的喜树碱衍生物的合成,发现通过氨基自由基反应不能直接在喜树碱7-位接上引入氨基,并提出了可能的解释。
Camptothecin(CPT) is a natural antitumor alkaloid isolated from Chinese tree Camptotheca acuminate.CPT and many of its derivatives are potent inhibitor of Topoisomerase I(Topo I).Their antitumor mechanism is that CPT and its derivatives could stabilize the Topo I-DNA complex and subsequently influence the republication of DNA and cause the cell death.During the last several decades, thousands of CPT derivatives were synthesized and their antitumor activities were evaluated.Three of the analogues Irinotecan,Topotecan and Belotecan have been approved as chemotherapeutic drugs used in clinic treatment on human cancers,and several other derivatives are now in different phases of clinic and pre-clinic trials. Base on the research on the structure-activity relationship(SAR) and reactive properties of CPT from literature,we have designed and synthesized 3 series of novel CPT analogues,and evaluated their antitumor activities to find promising new drugs.
1.Synthesis and biological evaluation of 7-cycloalkylcamptothecin derivatives
Substitutions especially lipophilic groups at 7-position of CPT have instinct properties for activity in human blood.They could stop the interaction of carboxylate form of CPT E-ring with human serum albumin(HSA),and as a result,stabilize the E-ring lactone,enhance the biological activities and reduce the side effects. Substitutions are generally attached to 7-position via radical reactions.We applied the radical alkylation of alkylbromide to synthesize 7-alkylcamptothecin derivatives and developed a novel route for preparation 7-alkylcamptothecin derivatives.With this new method,we used much cheaper and more facile starting materials to get comparable or even higher yield than the methods reported in preparing 7-cycloalkylcamptothecin analogues.The result of antitumor activities demonstrated that the synthetic compounds of 7-cycloalkylcamptothecin derivatives have high activity which even up to 40 times higher than reference drug Topotecan.The SAR matched the conclusion we achieved before with QSAR study.The exceptional compound 7-cyclooctyl camptothecin showed low activity,which might imply a different model of combination with biological macromolecular due to its steric bulks.
2.Synthesis and biological evaluation of E-ring opened camptothecin derivatives
An intact lactone E-ring was once considered to be indispensable for CPT's activity.However,recent investigations indicated that CPT E-ring opened derivatives "hydroxyl-amide" and "ester-amid" compounds have comparable activity with CPT itself.We firstly introduced morpholine and imidazole groups to CPT "hydroxyl-amide" and "ester-amid" derivatives with simple procedures,and prepared 10 E-ring opened CPT analogues.Biological evaluation in vitro presented that activities of "hydroxyl-amide" compounds with morpholine group were high than that with imidazole group,and in "ester-amid" compounds,propionate derivatives have higher activities than acetate analogues.7/10 substitutions enhance the activitiy of the E-ring opened derivatives.The inhibition of "hydroxyl-amide" 3-5a on transplanted human tumors in mice and nude mice showed higher efficacy than reference drugs.The biological evaluation implied that CPT "hydroxyl-amide" compounds have their intrinsic antitumor property,not just play as the pre-drug of its ring-closed parent CPT.
3.Synthesis and biological evaluation of E-ring five-membered lactone analogues of CPT
The high activities of homo-camptothecin and several E-ring modified CPT analogues change the opinions of the function of CPT E-ring.We designed and synthesized a series of E-ringγ-amide five-membered lactone analogues of CPT and evaluated their biological activity.The preparation of this series of compounds underwent a key procedure with three-step-tandem reaction.This domino reaction occurred on the PDC-CH_2Cl_2 condition after CPTs were opened by amines,and formed the target compounds.Derivatives bearing with terminal tertiary amines could not be achieved by the same strategy since tertiary amines were also oxidated by PDC.After different sequences were explored,the best strategy is connecting subsection to introduce tertiary amines.We gained more than 50γ-amide lactone analogues,including 7/10 substituted compounds,and 21 of them were tested to evaluate their activity.Disappointing,this E-ring modified CPT analogues presented low antitumor activity.Only one of them displayed comparable activity with reference drug Topotecan.Presumably,the 17-carbonyl in these compounds might compete with carbonyl in the D-ring in binding to biological macromolecular and caused the reduced activity.7/10 substitutions revealed two different contribution to the activity from SAR study,when butyl substituted at the N-amide,they favored the antitumor activity,but when the amide were substituted with tertiary amines,they disfavored the activities.
In addition,amine radical reaction was employed for exploring the pathway to prepare 7-N substituted CPT analogues,though failed.The possible explanation was presented.
引文
(1) 陈清奇编著 《美国抗癌药物化学合成速查》2009,科学出版社 2009年2月出版.
(2) 陈清奇编著 《抗癌新药研究指南》2009,科学出版社 2009年2月出版.
(3) Wall,M.E.;Wani,M.C.;Cook,C.E.;Palmer,K.H.;McPhail,A.T.;Sim,G.A.Journal of the American Chemical Society 1966,88,3888-3890.
(4) Wani,M.C.;Ronman,P.E.;Lindley,J.T.;Wall,M.E.Journal of Medicinal Chemistry 1980,23,554-560.
(5) Kessel,D.Biochem.Biophys.Acta 1971,246,225.
(6) Wu,R.S.;Kumar,A.;Warner,J.R.Proceedings of the National Academy of Sciences 1971,68,3009-3014.
(7) Hsiang,Y.H.;Hertzberg,R.;Hecht,S.;Liu,L.F.Journal of Biological Chemistry 1985,260,14873-14878.
(8) Jc,J.W.Annu Rev Biochem 1996,65,635-692.
(9) Liu,L.F.;Desai,S.D.;Li,T.;Mao,Y.;Sun,M.E.I.;Sim,S.Annals of the New York Academy of Sciences 2000,922,1-10.
(10) Ulukan,H.;Swaan,P.W.Drugs 2002,62,2039.
(11) Kerrigan,J.E.;Pilch,D.S.Biochemistry 2001,40,9792-9798.
(12) Thomas,C.J.;Rahier,N.J.;Hecht,S.M.Bioorganic & Medicinal Chemistry 2004,12,1585-1604.
(13) Capranico,G.;Ferri,F.;Fogli,M.V.;Russo,A.;Lotito,L.;Baranello,L.Biochimie 2007,89,482-489.
(14) Redinbo,M.R.;Stewart,L.;Kuhn,P.;Champoux,J.J.;Hol,W.G.J.Science 1998,279,1504.
(15) Staker,B.L.;Hjerrild,K.;Feese,M.D.;Behnke,C.A.;Burgin,A.B.;Stewart,L.Proceedings of the National Academy of Sciences of the United States of America 2002,99,15387-15392.
(16) Hertzberg,R.P.;Busby,R.W.;Caranfa,M.J.;Holden,K.G.;Johnson,R.K.;Hecht,S.M.;Kingsbury,W.D.Journal of Biological Chemistry 1990,265,19287-19295.
(17) Laco,G.S.;Collins,J.R.;Luke,B.T.;Kroth,H.;Sayer,J.M.;Jerina,D.M.;Pommier,Y.Biochemistry 2002,41,1428-1435.
(18) Kerrigan,J.E.;Pilch,D.S.Biochemistry 2001,40,9792-9798.
(19) Takimoto,C.H.;Wright,J.;Arbuck,S.G.BBA-Gene Structure and Expression 1998,1400,107-119.
(20) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1994,37,40-46.
(21) Opanasopit,P.;Yokoyama,M.;Watanabe,M.;Kawano,K.;Maitani,Y.;Okano,T.Journal of Controlled Release 2005,104,313-321.
(22) Sawada,S.;Okajima,S.;Aiyama,R.;Nokata,K.;Furuta,T.;Yokokura,T.;Sugino,E.;Yamaguchi,K.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,1446-1454.
(23) Kingsbury,W.D.;Boehm,J.C.;Jakas,D.R.;Holden,K.G.;Hecht,S.M.;Gallagher,G.;Caranfa,M.J.;Mccabe,F.L.;Faucette,L.F.;Johnson,R.K.;Hertzberg,R.P.Journal of Medicinal Chemistry 1991,34,98-107.
(24) Kim,J.C.;Shin,D.H.;Kim,S.H.;Kim,J.K.;Park,S.C.;Son,W.C.;Lee,H.S.;Suh,J.E.;Kim,C.Y.;Ha,C.S.;Chung,M.K.Regulatory Toxicology and Pharmacology 2004,40,356-369.
(25) Rasheed,Z.A.;Rubin,E.H.Oncogene 2003,22,7296-7304.
(26) Lorence,A.;Nessler,C.L.Phytochemistry 2004,65,2735-2749.
(27) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1986,29,2358-2363.
(28) Kingsbury,W.D.;Boehm,J.C.;Jakas,D.R.;Holden,K.G.;Hecht,S.M.;Gallagher,G.;Caranfa,M.J.;McCabe,F.L.;Faueette,L.F.;Johnson,R.K.;Hertzberg,R.P.Journal of Medicinal Chemistry 1991,34,98-107.
(29) Sawada,S.;Matsuoka,S.;Nokata,K.;Nagata,H.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,3183-3188.
(30) Fu,Q.;Chen,Z.Synthesis(Stuttgart) 2006,1940-1942.
(31) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(32) Subrahmanyam,D.;Venkateswarlu,A.;Rao,K.V.;Sastry,T.V.R.S.;Vandana,G.;Kumar,S.A.Bioorganic & Medicinal Chemistry Letters 1999,9,1633-1638.
(33) Comins,D.L.;Baevsky,M.F.;Hong,H.Journal of the American Chemical Society 1992,114,10971-10972.
(34) Curran,D.P.;Liu,H.Journal of the American Chemical Society 1992,114,5863-5864.
(35) Shen,W.;Coburn,C.A.;Bornmann,W.G.;Danishefsky,S.J.The Journal of Organic Chemistry 1993,58,611-617.
(36) Chavan,S.P.;Sivappa,R.Tetrahedron Letters 2004,45,3113-3115.
(37) Ejima,A.;Terasawa,H.;Sugimori,M.;Tagawa,H.Journal of the Chemical Society-Perkin Transactions 1 1990,27-31.
(38) Chavan,S.P.;Venkatraman,M.S.Tetrahedron Letters 1998,39,6745-6748.v(39) Brown,R.T.;Liu,J.L.;Santos,C.A.M.Tetrahedron Letters 2000,41,859-862.
(40) Tagami,K.;Nakazawa,N.;Sano,S.;Nagao,Y.Heterocycles 2000,53,771-775.
(41) Tang,C.S.F.;Morrow,C.J.;Rapoport,H.Journal of the American Chemical Society 1975,97,159-167.
(42) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,2317-2319.
(43) Imura,A.;Itoh,M.;Miyadera,A.Tetrahedron:Asymmetry 1998,9,2285-2291.
(44) 高河勇;孙婧;李倩;吕伟;蔡俊超 中国医药工业杂志 2005,36,106-114.
(45) Yabu,K.;Masumoto,S.;Kanai,M.;Curran,D.P.;Shibasaki,M.Tetrahedron Letters 2002,43,2923-2926.
(46) Yabu,K.;Masumoto,S.;Yamasaki,S.;Hamashima,Y.;Kanai,M.;Du,W.;Curran,D.P.;Shibasaki,M.Journal of the American Chemical Society 2001,123,9908-9909.
(47) Comins,D.L.;Saha,J.K.Tetrahedron Letters 1995,36,7995-7998.
(48) Comins,D.L.;Nolan,J.M.Organic Letters 2001,3,4255-4257.
(49) Fang,F.G.;Xie,S.P.;Lowery,M.W.Journal of Organic Chemistry 1994,59,6142-6143.
(50) Jew,S.S.;Ok,K.D.;Kim,H.J.;Kim,M.G.;Kim,J.M.;Hah,J.M.;Cho,Y.S.Tetrahedron-Asymmetry 1995,6,1245-1248.
(51) Blagg,B.S.J.;Boger,D.L.Tetrahedron 2002,58,6343-6349.
(52) Imura,A.;Itoh,M.;Miyadera,A.Tetrahedron-Asymmetry 1998,9,2285-2291.
(53) 李连强;潘夕春;锋,谈.中草药 2006,37,623-626.
(54) Leu,Y.L.;Roffler,S.R.;Chern,J.W.Journal of Medicinal Chemistry 1999,42,3623-3628.
(55) Carrigan,S.W.;Fox,P.C.;Wall,M.E.;Wani,M.C.;Bowen,J.P.Journal of Computer-Aided Molecular Design 1997,11,71-78.
(56) Wall,M.E.;Wani,M.C.;Nicholas,A.W.;Manikumar,G.;Tele,C.;Moore,L.;Truesdale,A.;Leitner,P.;Besterman,J.M.Journal of Medicinal Chemistry 1993,36,2689-2700.
(57) Wani,M.C.;Nicholas,A.W.;Manikumar,G.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,1774-1779.
(58) Kim,D.K.;Lee,N.Mini Reviews in Medicinal Chemistry 2002,2,611-619.
(59) Tanizawa,A.;Kohn,K.W.,Kohlhagen,G.;Leteurtre,F.;Pommier,Y.Biochemistry 1995,34,7200-7206.
(60) Subrahmanyam,D.;Sarma,V.M.;Venkateswarlu,A.;Sastry,T.;Kulakami,A.P.;Srinivasa Rao,D.;Krishna Reddy,K.Bioorganic & Medicinal Chemistry 1999,7,2013-2020.
(61) Sriram,D.;Yogeeswari,P.;Thirumurugan,R.;Bal,T.R.Natural Product Research 2005,19,393-412.
(62) Subrahmanyam,D.;Sarma,V.M.;Venkateswarlu,A.;Sastry,T.V.R.S.;Srinivas,A.S.S.V.;Krishna,C.V.;Deevi,D.S.;Kumar,S.A.;Babu,M.J.;Damodaran,N.K.Bioorganic &Medicinal Chemistry Letters 2000,10,369-371.
(63) Sugimori,M.;Ejima,A.;Ohsuki,S.;Matsumoto,K.;Kawato,Y.;Yasuoka,M.;Tagawa,H.;Terasawa,H.Heterocycles 1994,38,81-94.
(64) Nicholas,A.W.;Wani,M.C.;Manikumar,G.;Wall,M.E.,Kohn,K.W.;Pommier,Y.Journal of Medicinal Chemistry 1990,33,972-978.
(65) Rahier,N.J.;Cheng,K.;Gao,R.;Eisenhauer,B.M.;Hecht,S.M.Org.Lett 2005,7,835-837.
(66) Qing-yong,L.I.;Yuan-gang,Z.U.;Rong-zhen,S.H.I.;Yao,L.P.Curr Med Chem 2006,13,2021-2039.
(67) Crow,R.T.;Crothers,D.M.Journal of Medicinal Chemistry 1992,35,4160-4164.
(68) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,2317-2319.
(69) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1993,36,2580-2582.
(70) Mi,Z.;Burke,T.G.Biochemistry 1994,33,10325-10336.
(71) Burke,T.G.;Munshi,C.B.;Mi,Z.H.,Jiang,Y.Journal of Pharmaceutical Sciences 1995,84,518-519.
(72) Hertzberg,R.P.;Caranfa,M.J.;Holden,K.G.;Jakas,D.R.;Gallagher,G.;Mattern,M.R.;Mong,S.M.;Bartus,J.O.L.;Johnson,R.K.;Kingsbury,W.D.Journal of Medicinal Chemistry 1989,32,715-720.
(73) Cao,Z.;Harris,N.;Kozielski,A.;Vardeman,D.;Stehlin,J.S.;Giovanella,B.Journal of Medicinal Chemistry 1998,41,31-37.
(74) Cao,Z.S.;Pantazis,P.;Mendoza,J.;Early,J.;Kozielski,A.;Harris,N.;Vardeman,D.,Liehr,J.;Stehlin,J.S.;Giovanella,B.Camptothecins:Unfolding Their Anticancer Potential 2000,922,122-135.
(75) Wang,C.Y.;Pan,X.D.;Liu,H.Y.;Fu,Z.D.;Wei,X.Y.;Yang,L.X.Bioorganic & Medicinal Chemistry 2004,12,3657-3662.
(76) Takimoto,C.H.;Thomas,R.Annals of the New York Academy of Sciences-Paper Edition 2000,922,224-236.
(77) Verschraegen,C.;Gupta,E.;Loyer,E.,Kavanagh,J.J.;Kudelka,A.P.;Freedman,R.S.;Edwards,C.L.;Harris,N.;Steger,M.;Steltz,V.Anticancer Drugs 1999,10,375-384.
(78) Mitsui,I.;Kumazawa,E.;Hirota,Y.;Aonuma,M.;Sugimori,M.;Ohsuki,S.;Uoto,K.;Ejima,
(1) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(2) Sawada,S.;Okajima,S.;Aiyama,R.;Nokata,K.;Furuta,T.;Yokokura,T.;Sugino,E.;Yamaguchi,K.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,1446-1454.
(3) Jew,S.S.;Kim,M.G.;Kim,H.J.;Roh,E.Y.;Cho,Y.S.;Kim,J.K.;Cha,K.H.;Lee,K.K.;Han,H.J.;Lee,H.Bioorganic & Medicinal Chemistry Letters 1996,6,849-852.
(4) Josien,H.;Born,D.;Curran,D.P.;Zheng,Y.H.;Chou,T.C.Bioorganic & Medicinal Chemistry Letters 1997,7,3189-3194.
(5) Ohtsu,H.;Nakanishi,Y.;Bastow,K.F.;Lee,F.Y.;Lee,K.H.Bioorganic & Medicinal Chemistry 2003,11,1851-1857.
(6) Luo,Y.;Gao,H.;Li,Y.;Huang,W.;Lu,W.;Zhang,Z.Tetrahedron 2006,62,2465-2470.
(7) Dallavalle,S.;Merlini,L.;Morini,G.;Musso,L.;Penco,S.;Beretta,G.L.;Tinelli,S.;Zunino,F.European Journal of Medicinal Chemistry 2004,39,507-513.
(8) Dallavalle,S.;Giannini,G.;Alloatti,D.;Casati,A.;Marastoni,E.;Musso,L.;Merlini,L.;Morini,G.;Penco,S.;Pisano,C.;Tinelli,S.;De Cesare,M.;Beretta,G.L.;Zunino,F.Journal of Medicinal Chemistry 2006,49,5177-5186.
(9) Bom,D.;Curran,D.P.;Kruszewski,S.;Zimmer,S.G.;Strode,J.T.;Kohlhagen,G.;Du,W.;Chavan,A.J.;Fraley,K.A.;Bingcang,A.L.J.med.Chem 2000,43,3970-3980.
(10) Burke,T.G.;Mi,Z.H.Analytical Biochemistry 1993,212,285-287.
(11) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1994,37,40-46.
(12) Mi,Z.;Malak,H.;Burke,T.G.Biochemistry 1995,34,13722-13728.
(13) Josien,H.;Ko,S.B.;Bom,D.;Curran,D.P.Chemistry-a European Journal 1998,4,67-83.
(14) Curran,D.P.;Liu,H.;Josien,H.;Ko,S.B.Tetrahedron 1996,52,11385-11404.
(15) Manikumar,G.;Wadkins,R.M.;Bearss,D.;Von Hoff,D.D.;Wani,M.C.;Wall,M.E.Bioorganic & Medicinal Chemistry Letters 2004,14,5377-5381.
(16) Giovanella,B.C.;Stehlin,J.S.;Wall,M.E.;Wani,M.C.;Nicholas,A.W.;Liu,L.F.;Silber,R.;Potmesil,M.Science 1989,246,1046-1048.
(17) Tanizawa,A.;Fujimori,A.;Fujimori,Y.;Pommier,Y.Journal of the National Cancer Institute 1994,86,836-842.
(18) Li,M.J.;Jiang,C.;Li,M.Z.;You,T.P.Journal of Molecular Structure-Theochem 2005,723,165-170.
(19) Redinbo,M.R.;Stewart,L.;Kuhn,P.;Champoux,J.J.;Hol,W.G.J.Science 1998,279,1504.
(20) Fan,Y.;Weinstein,J.N.;Kohn,K.W.;Shi,L.M.;Pommier,Y.Journal of Medicinal Chemistry 1998,41,2216-2226.
(21) 雷英杰 天津理工学院学报 2004,20,106-108.
(22) Grummitt;;Liska;;Greull;Organic Syntheses 1964,44.
(23) Wang,X.;Wen,J.W.;Li,G.;You,T.P.Synthetic Communications 2005,35,3163-3166.
(24) Wang,X.;Wu,X.J.;Cheng,N.;Zhao,H.Q.;Gu,Z.H.;Shen,X.A.Synthetic Communications 2007,37,519-523.
(25) Citterio,A.;Minisci,F.The Journal of Organic Chemistry 1982,47,1759-1761.
(26) Minisci,F.;Vismara,E.;Fontana,F.;Morini,G.;Serravalle,M.;Giordano,C.The Journal of Organic Chemistry 1986,51,4411-4416.
(27) Minisci,F.;Vismara,E.;Fontana,F.The Journal of Organic Chemistry 1989,54,5224-5227.
(28) Minisci,F.;Coppa,F.;Fontana,F.;Pianese,G.;Zhao,L.The Journal of Organic Chemistry 1992,57,3929-3933.
(29) Minisci,F.;Fontana,F.;Pianese,G.;Yan,Y.M.The Journal of Organic Chemistry 1993,58,4207-4211.
(30) Minisci,F.;Porta,O.;Katryzky,A.;Boilton,A.J.1974.
(31) Vladu,B.;Woynarowski,J.M.;Manikumar,G.;Wani,M.C.;Wall,M.E.;Von Hoff,D.D.;Wadkins,R.M.Molecular Pharmacology 2000,57,243-251.
(1) Adamovics,J.A.;Hutchinson,C.R.Journal of Medicinal Chemistry 1979,22,310-314.
(2) Greenwald,R.B.;Zhao,H.;Xia,J.Bioorganic & Medicinal Chemistry 2003,11,2635-2639.
(1) Govindachari,T.R.R.,K.R.;Viswanathan,N.J Chem.Soc.,Perkin Trans.1 1974,1215.
(2) Hertzberg,R.P.;Caranfa,M.J.;Holden,K.G.;Jakas,D.R.;Gallagher,G.;Mattern,M.R.;Mong,S.M.;Bartus,J.O.L.;Johnson,R.K.;Kingsbury,W.D.Journal of Medicinal Chemistry 1989,32,715-720.
(3) Du,W.;Curran,D.P.;Bevins,R.L.;Zimmer,S.G.;Zhang,J.H.;Burke,T.G.Bioorganic &Medicinal Chemistry 2002,10,103-110.
(4) Hautefaye,P.;Cimetiere,B.;Pierre,A.;Leonce,S.;Hickman,J.;Laine,W.;Bailly,C.;Lavielle,G.Bioorganic & Medicinal Chemistry Letters 2003,13,2731-2735.
(5) Lin,L.Z.;Cordell,G.A.Phytochemistry 1989,28,1295.
(6) Grillet,F.;Baumlov(?),B.;Pr(?)vost,G.;Constant,J.F.;Chaumeron,S.;Bigg,D.C.H.;Greene,A.E.;Kanazawa,A.Bioorganic & Medicinal Chemistry Letters 2008,18,2143-2146.
(7) Org.Syn.Col.Vol.Ⅴ,1973,310.
(8) Tetrahedron Letters 1969,10,3363.
(9) Piancatelli,G.;Scettri,A.;D'Auria,M.Synthesis 1982,1982,245-258.
(10) Czernecki,S.;Georgoulis,C.;Stevens,C.L.;Vijayakumaran,K.Tetrahedron Letters 1985,26,1699-1702.
(11) Lee,T.V.Comprehensive Organic Synthesis 1991,7.
(12) Khuddus,M.A.;Swern,D.J Am Chem Soc 1973,95,8393-8402.
(13) Pfitzner,K.E.;Moffatt,J.G.J.Am.Chem.Soc 1965,87,5661-5670.
(14) Corey,E.J.;Kim,C.U.J.Am.Chem.Soc 1972,94,7586-7587.
(15) Tangirala,R.S.;Antony,S.;Agama,K.;Pommier,Y.;Anderson,B.D.;Bevins,R.;Curran,D.P.Bioorganic & Medicinal Chemistry 2006,14,6202-6212.
(16) 雷英杰 天津理工学院学报 2004,20,106-108.
(17) LaRock,R.;Wiley-VCH Publishers,New York,Weinheim:1999.
(1) 王葆仁;有机合成反应 科学出版社:北京,1985.
(2) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(3) Miyasaka,T.;Sawada,S.;Nokata,K.-i.Heterocycles 1981,16,1719-1721.
(4) Lackey,K.;Besterman,J.M.;Fletcher,W.;Leitner,P.;Morton,B.;Sternbach,D.D.Journal of Medicinal Chemistry 1995,38,906-911.
(5) Ashby,E.C.;Park,B.;Patil,G.S.;Gadru,K.;Gurumurthy,R..The Journal of Organic Chemistry 1993,58,424-437.
(6) Lavergne,O.;LesueurGinot,L.;R.odas,F.P.;Bigg,D.C.H.Bioorganic & Medicinal Chemistry Letters 1997,7,2235-2238.
(7) Lavergne,O.;Lesueur-Ginot,L.;Rodas,F.P.;Kasprzyk,P.G.;Pommier,J.;Demarquay,D.;Prevost,G.;Ulibarri,G.;Rolland,A.;Schiano-Liberatore,A.M.;Harnett,J.;Pons,D.;Camara,J.;Bigg,D.C.H.Journal of Medicinal Chemistry 1998,41,5410-5419.
(8) Born,D.;Curran,D.P.;Chavan,A.J.;Kruszewski,S.;Zimmer,S.G.;Fraley,K.A.;Burke,T.G.J.med.Chem 1999,42,3018-3022.
(9) Lavergne,O.;Demarquay,D.;Kasprzyk,P.G.;Bigg,D.C.H.Annals of the New York Academy of Sciences 2000,922,100-111.
(10) Lesueur-Ginot,L.;Demarquay,D.;Kiss,R.;Kasprzyk,P.G.;Dassonneville,L.;Bailly,C.;Camara,J.;Lavergne,O.;Bigg,D.C.H.Cancer Research 1999,59,2939-2943.
(11) Lavergne,O.;Harnett,J.;Rolland,A.;Lanco,C.;Lesueur-Ginot,L.;Demarquay,D.;Huchet,M.;Coulomb,H.;Bigg,D.C.H.Bioorganic & medicinal chemistry letters(Print) 1999,9,2599-2602.
(12) Demarquay,D.;Coulomb,H.;Huchet,M.;Lesueur-Ginot,L.;Camara,J.;Lavergne,O.;Bigg,D.Annals of the New York Academy of Sciences 2000,922,301-302.
(13) Gabarda,A.E.;Du,W.;Isarno,T.;Tangirala,R.S.;Curran,D.P.Tetrahedron 2002,58,6329-6341.
(14) Peters,R.;Althaus,M.;Diolez,C.;Rolland,A.;Manginot,E.;Veyrat,M.The Journal of Organic Chemistry 2006,71,7583-7595.
(15) Arndt,F.;Eistert,B.Berichte der deutschen chemischen Gesellschaft(A and B Series) 1935,68.
(16) Kirmse,W.European Journal Of Organic Chemistry 2002.
(2) 陈清奇编著 《抗癌新药研究指南》2009,科学出版社 2009年2月出版.
(3) Wall,M.E.;Wani,M.C.;Cook,C.E.;Palmer,K.H.;McPhail,A.T.;Sim,G.A.Journal of the American Chemical Society 1966,88,3888-3890.
(4) Wani,M.C.;Ronman,P.E.;Lindley,J.T.;Wall,M.E.Journal of Medicinal Chemistry 1980,23,554-560.
(5) Kessel,D.Biochem.Biophys.Acta 1971,246,225.
(6) Wu,R.S.;Kumar,A.;Warner,J.R.Proceedings of the National Academy of Sciences 1971,68,3009-3014.
(7) Hsiang,Y.H.;Hertzberg,R.;Hecht,S.;Liu,L.F.Journal of Biological Chemistry 1985,260,14873-14878.
(8) Jc,J.W.Annu Rev Biochem 1996,65,635-692.
(9) Liu,L.F.;Desai,S.D.;Li,T.;Mao,Y.;Sun,M.E.I.;Sim,S.Annals of the New York Academy of Sciences 2000,922,1-10.
(10) Ulukan,H.;Swaan,P.W.Drugs 2002,62,2039.
(11) Kerrigan,J.E.;Pilch,D.S.Biochemistry 2001,40,9792-9798.
(12) Thomas,C.J.;Rahier,N.J.;Hecht,S.M.Bioorganic & Medicinal Chemistry 2004,12,1585-1604.
(13) Capranico,G.;Ferri,F.;Fogli,M.V.;Russo,A.;Lotito,L.;Baranello,L.Biochimie 2007,89,482-489.
(14) Redinbo,M.R.;Stewart,L.;Kuhn,P.;Champoux,J.J.;Hol,W.G.J.Science 1998,279,1504.
(15) Staker,B.L.;Hjerrild,K.;Feese,M.D.;Behnke,C.A.;Burgin,A.B.;Stewart,L.Proceedings of the National Academy of Sciences of the United States of America 2002,99,15387-15392.
(16) Hertzberg,R.P.;Busby,R.W.;Caranfa,M.J.;Holden,K.G.;Johnson,R.K.;Hecht,S.M.;Kingsbury,W.D.Journal of Biological Chemistry 1990,265,19287-19295.
(17) Laco,G.S.;Collins,J.R.;Luke,B.T.;Kroth,H.;Sayer,J.M.;Jerina,D.M.;Pommier,Y.Biochemistry 2002,41,1428-1435.
(18) Kerrigan,J.E.;Pilch,D.S.Biochemistry 2001,40,9792-9798.
(19) Takimoto,C.H.;Wright,J.;Arbuck,S.G.BBA-Gene Structure and Expression 1998,1400,107-119.
(20) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1994,37,40-46.
(21) Opanasopit,P.;Yokoyama,M.;Watanabe,M.;Kawano,K.;Maitani,Y.;Okano,T.Journal of Controlled Release 2005,104,313-321.
(22) Sawada,S.;Okajima,S.;Aiyama,R.;Nokata,K.;Furuta,T.;Yokokura,T.;Sugino,E.;Yamaguchi,K.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,1446-1454.
(23) Kingsbury,W.D.;Boehm,J.C.;Jakas,D.R.;Holden,K.G.;Hecht,S.M.;Gallagher,G.;Caranfa,M.J.;Mccabe,F.L.;Faucette,L.F.;Johnson,R.K.;Hertzberg,R.P.Journal of Medicinal Chemistry 1991,34,98-107.
(24) Kim,J.C.;Shin,D.H.;Kim,S.H.;Kim,J.K.;Park,S.C.;Son,W.C.;Lee,H.S.;Suh,J.E.;Kim,C.Y.;Ha,C.S.;Chung,M.K.Regulatory Toxicology and Pharmacology 2004,40,356-369.
(25) Rasheed,Z.A.;Rubin,E.H.Oncogene 2003,22,7296-7304.
(26) Lorence,A.;Nessler,C.L.Phytochemistry 2004,65,2735-2749.
(27) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1986,29,2358-2363.
(28) Kingsbury,W.D.;Boehm,J.C.;Jakas,D.R.;Holden,K.G.;Hecht,S.M.;Gallagher,G.;Caranfa,M.J.;McCabe,F.L.;Faueette,L.F.;Johnson,R.K.;Hertzberg,R.P.Journal of Medicinal Chemistry 1991,34,98-107.
(29) Sawada,S.;Matsuoka,S.;Nokata,K.;Nagata,H.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,3183-3188.
(30) Fu,Q.;Chen,Z.Synthesis(Stuttgart) 2006,1940-1942.
(31) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(32) Subrahmanyam,D.;Venkateswarlu,A.;Rao,K.V.;Sastry,T.V.R.S.;Vandana,G.;Kumar,S.A.Bioorganic & Medicinal Chemistry Letters 1999,9,1633-1638.
(33) Comins,D.L.;Baevsky,M.F.;Hong,H.Journal of the American Chemical Society 1992,114,10971-10972.
(34) Curran,D.P.;Liu,H.Journal of the American Chemical Society 1992,114,5863-5864.
(35) Shen,W.;Coburn,C.A.;Bornmann,W.G.;Danishefsky,S.J.The Journal of Organic Chemistry 1993,58,611-617.
(36) Chavan,S.P.;Sivappa,R.Tetrahedron Letters 2004,45,3113-3115.
(37) Ejima,A.;Terasawa,H.;Sugimori,M.;Tagawa,H.Journal of the Chemical Society-Perkin Transactions 1 1990,27-31.
(38) Chavan,S.P.;Venkatraman,M.S.Tetrahedron Letters 1998,39,6745-6748.v(39) Brown,R.T.;Liu,J.L.;Santos,C.A.M.Tetrahedron Letters 2000,41,859-862.
(40) Tagami,K.;Nakazawa,N.;Sano,S.;Nagao,Y.Heterocycles 2000,53,771-775.
(41) Tang,C.S.F.;Morrow,C.J.;Rapoport,H.Journal of the American Chemical Society 1975,97,159-167.
(42) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,2317-2319.
(43) Imura,A.;Itoh,M.;Miyadera,A.Tetrahedron:Asymmetry 1998,9,2285-2291.
(44) 高河勇;孙婧;李倩;吕伟;蔡俊超 中国医药工业杂志 2005,36,106-114.
(45) Yabu,K.;Masumoto,S.;Kanai,M.;Curran,D.P.;Shibasaki,M.Tetrahedron Letters 2002,43,2923-2926.
(46) Yabu,K.;Masumoto,S.;Yamasaki,S.;Hamashima,Y.;Kanai,M.;Du,W.;Curran,D.P.;Shibasaki,M.Journal of the American Chemical Society 2001,123,9908-9909.
(47) Comins,D.L.;Saha,J.K.Tetrahedron Letters 1995,36,7995-7998.
(48) Comins,D.L.;Nolan,J.M.Organic Letters 2001,3,4255-4257.
(49) Fang,F.G.;Xie,S.P.;Lowery,M.W.Journal of Organic Chemistry 1994,59,6142-6143.
(50) Jew,S.S.;Ok,K.D.;Kim,H.J.;Kim,M.G.;Kim,J.M.;Hah,J.M.;Cho,Y.S.Tetrahedron-Asymmetry 1995,6,1245-1248.
(51) Blagg,B.S.J.;Boger,D.L.Tetrahedron 2002,58,6343-6349.
(52) Imura,A.;Itoh,M.;Miyadera,A.Tetrahedron-Asymmetry 1998,9,2285-2291.
(53) 李连强;潘夕春;锋,谈.中草药 2006,37,623-626.
(54) Leu,Y.L.;Roffler,S.R.;Chern,J.W.Journal of Medicinal Chemistry 1999,42,3623-3628.
(55) Carrigan,S.W.;Fox,P.C.;Wall,M.E.;Wani,M.C.;Bowen,J.P.Journal of Computer-Aided Molecular Design 1997,11,71-78.
(56) Wall,M.E.;Wani,M.C.;Nicholas,A.W.;Manikumar,G.;Tele,C.;Moore,L.;Truesdale,A.;Leitner,P.;Besterman,J.M.Journal of Medicinal Chemistry 1993,36,2689-2700.
(57) Wani,M.C.;Nicholas,A.W.;Manikumar,G.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,1774-1779.
(58) Kim,D.K.;Lee,N.Mini Reviews in Medicinal Chemistry 2002,2,611-619.
(59) Tanizawa,A.;Kohn,K.W.,Kohlhagen,G.;Leteurtre,F.;Pommier,Y.Biochemistry 1995,34,7200-7206.
(60) Subrahmanyam,D.;Sarma,V.M.;Venkateswarlu,A.;Sastry,T.;Kulakami,A.P.;Srinivasa Rao,D.;Krishna Reddy,K.Bioorganic & Medicinal Chemistry 1999,7,2013-2020.
(61) Sriram,D.;Yogeeswari,P.;Thirumurugan,R.;Bal,T.R.Natural Product Research 2005,19,393-412.
(62) Subrahmanyam,D.;Sarma,V.M.;Venkateswarlu,A.;Sastry,T.V.R.S.;Srinivas,A.S.S.V.;Krishna,C.V.;Deevi,D.S.;Kumar,S.A.;Babu,M.J.;Damodaran,N.K.Bioorganic &Medicinal Chemistry Letters 2000,10,369-371.
(63) Sugimori,M.;Ejima,A.;Ohsuki,S.;Matsumoto,K.;Kawato,Y.;Yasuoka,M.;Tagawa,H.;Terasawa,H.Heterocycles 1994,38,81-94.
(64) Nicholas,A.W.;Wani,M.C.;Manikumar,G.;Wall,M.E.,Kohn,K.W.;Pommier,Y.Journal of Medicinal Chemistry 1990,33,972-978.
(65) Rahier,N.J.;Cheng,K.;Gao,R.;Eisenhauer,B.M.;Hecht,S.M.Org.Lett 2005,7,835-837.
(66) Qing-yong,L.I.;Yuan-gang,Z.U.;Rong-zhen,S.H.I.;Yao,L.P.Curr Med Chem 2006,13,2021-2039.
(67) Crow,R.T.;Crothers,D.M.Journal of Medicinal Chemistry 1992,35,4160-4164.
(68) Wani,M.C.;Nicholas,A.W.;Wall,M.E.Journal of Medicinal Chemistry 1987,30,2317-2319.
(69) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1993,36,2580-2582.
(70) Mi,Z.;Burke,T.G.Biochemistry 1994,33,10325-10336.
(71) Burke,T.G.;Munshi,C.B.;Mi,Z.H.,Jiang,Y.Journal of Pharmaceutical Sciences 1995,84,518-519.
(72) Hertzberg,R.P.;Caranfa,M.J.;Holden,K.G.;Jakas,D.R.;Gallagher,G.;Mattern,M.R.;Mong,S.M.;Bartus,J.O.L.;Johnson,R.K.;Kingsbury,W.D.Journal of Medicinal Chemistry 1989,32,715-720.
(73) Cao,Z.;Harris,N.;Kozielski,A.;Vardeman,D.;Stehlin,J.S.;Giovanella,B.Journal of Medicinal Chemistry 1998,41,31-37.
(74) Cao,Z.S.;Pantazis,P.;Mendoza,J.;Early,J.;Kozielski,A.;Harris,N.;Vardeman,D.,Liehr,J.;Stehlin,J.S.;Giovanella,B.Camptothecins:Unfolding Their Anticancer Potential 2000,922,122-135.
(75) Wang,C.Y.;Pan,X.D.;Liu,H.Y.;Fu,Z.D.;Wei,X.Y.;Yang,L.X.Bioorganic & Medicinal Chemistry 2004,12,3657-3662.
(76) Takimoto,C.H.;Thomas,R.Annals of the New York Academy of Sciences-Paper Edition 2000,922,224-236.
(77) Verschraegen,C.;Gupta,E.;Loyer,E.,Kavanagh,J.J.;Kudelka,A.P.;Freedman,R.S.;Edwards,C.L.;Harris,N.;Steger,M.;Steltz,V.Anticancer Drugs 1999,10,375-384.
(78) Mitsui,I.;Kumazawa,E.;Hirota,Y.;Aonuma,M.;Sugimori,M.;Ohsuki,S.;Uoto,K.;Ejima,
(1) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(2) Sawada,S.;Okajima,S.;Aiyama,R.;Nokata,K.;Furuta,T.;Yokokura,T.;Sugino,E.;Yamaguchi,K.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,1446-1454.
(3) Jew,S.S.;Kim,M.G.;Kim,H.J.;Roh,E.Y.;Cho,Y.S.;Kim,J.K.;Cha,K.H.;Lee,K.K.;Han,H.J.;Lee,H.Bioorganic & Medicinal Chemistry Letters 1996,6,849-852.
(4) Josien,H.;Born,D.;Curran,D.P.;Zheng,Y.H.;Chou,T.C.Bioorganic & Medicinal Chemistry Letters 1997,7,3189-3194.
(5) Ohtsu,H.;Nakanishi,Y.;Bastow,K.F.;Lee,F.Y.;Lee,K.H.Bioorganic & Medicinal Chemistry 2003,11,1851-1857.
(6) Luo,Y.;Gao,H.;Li,Y.;Huang,W.;Lu,W.;Zhang,Z.Tetrahedron 2006,62,2465-2470.
(7) Dallavalle,S.;Merlini,L.;Morini,G.;Musso,L.;Penco,S.;Beretta,G.L.;Tinelli,S.;Zunino,F.European Journal of Medicinal Chemistry 2004,39,507-513.
(8) Dallavalle,S.;Giannini,G.;Alloatti,D.;Casati,A.;Marastoni,E.;Musso,L.;Merlini,L.;Morini,G.;Penco,S.;Pisano,C.;Tinelli,S.;De Cesare,M.;Beretta,G.L.;Zunino,F.Journal of Medicinal Chemistry 2006,49,5177-5186.
(9) Bom,D.;Curran,D.P.;Kruszewski,S.;Zimmer,S.G.;Strode,J.T.;Kohlhagen,G.;Du,W.;Chavan,A.J.;Fraley,K.A.;Bingcang,A.L.J.med.Chem 2000,43,3970-3980.
(10) Burke,T.G.;Mi,Z.H.Analytical Biochemistry 1993,212,285-287.
(11) Burke,T.G.;Mi,Z.Journal of Medicinal Chemistry 1994,37,40-46.
(12) Mi,Z.;Malak,H.;Burke,T.G.Biochemistry 1995,34,13722-13728.
(13) Josien,H.;Ko,S.B.;Bom,D.;Curran,D.P.Chemistry-a European Journal 1998,4,67-83.
(14) Curran,D.P.;Liu,H.;Josien,H.;Ko,S.B.Tetrahedron 1996,52,11385-11404.
(15) Manikumar,G.;Wadkins,R.M.;Bearss,D.;Von Hoff,D.D.;Wani,M.C.;Wall,M.E.Bioorganic & Medicinal Chemistry Letters 2004,14,5377-5381.
(16) Giovanella,B.C.;Stehlin,J.S.;Wall,M.E.;Wani,M.C.;Nicholas,A.W.;Liu,L.F.;Silber,R.;Potmesil,M.Science 1989,246,1046-1048.
(17) Tanizawa,A.;Fujimori,A.;Fujimori,Y.;Pommier,Y.Journal of the National Cancer Institute 1994,86,836-842.
(18) Li,M.J.;Jiang,C.;Li,M.Z.;You,T.P.Journal of Molecular Structure-Theochem 2005,723,165-170.
(19) Redinbo,M.R.;Stewart,L.;Kuhn,P.;Champoux,J.J.;Hol,W.G.J.Science 1998,279,1504.
(20) Fan,Y.;Weinstein,J.N.;Kohn,K.W.;Shi,L.M.;Pommier,Y.Journal of Medicinal Chemistry 1998,41,2216-2226.
(21) 雷英杰 天津理工学院学报 2004,20,106-108.
(22) Grummitt;;Liska;;Greull;Organic Syntheses 1964,44.
(23) Wang,X.;Wen,J.W.;Li,G.;You,T.P.Synthetic Communications 2005,35,3163-3166.
(24) Wang,X.;Wu,X.J.;Cheng,N.;Zhao,H.Q.;Gu,Z.H.;Shen,X.A.Synthetic Communications 2007,37,519-523.
(25) Citterio,A.;Minisci,F.The Journal of Organic Chemistry 1982,47,1759-1761.
(26) Minisci,F.;Vismara,E.;Fontana,F.;Morini,G.;Serravalle,M.;Giordano,C.The Journal of Organic Chemistry 1986,51,4411-4416.
(27) Minisci,F.;Vismara,E.;Fontana,F.The Journal of Organic Chemistry 1989,54,5224-5227.
(28) Minisci,F.;Coppa,F.;Fontana,F.;Pianese,G.;Zhao,L.The Journal of Organic Chemistry 1992,57,3929-3933.
(29) Minisci,F.;Fontana,F.;Pianese,G.;Yan,Y.M.The Journal of Organic Chemistry 1993,58,4207-4211.
(30) Minisci,F.;Porta,O.;Katryzky,A.;Boilton,A.J.1974.
(31) Vladu,B.;Woynarowski,J.M.;Manikumar,G.;Wani,M.C.;Wall,M.E.;Von Hoff,D.D.;Wadkins,R.M.Molecular Pharmacology 2000,57,243-251.
(1) Adamovics,J.A.;Hutchinson,C.R.Journal of Medicinal Chemistry 1979,22,310-314.
(2) Greenwald,R.B.;Zhao,H.;Xia,J.Bioorganic & Medicinal Chemistry 2003,11,2635-2639.
(1) Govindachari,T.R.R.,K.R.;Viswanathan,N.J Chem.Soc.,Perkin Trans.1 1974,1215.
(2) Hertzberg,R.P.;Caranfa,M.J.;Holden,K.G.;Jakas,D.R.;Gallagher,G.;Mattern,M.R.;Mong,S.M.;Bartus,J.O.L.;Johnson,R.K.;Kingsbury,W.D.Journal of Medicinal Chemistry 1989,32,715-720.
(3) Du,W.;Curran,D.P.;Bevins,R.L.;Zimmer,S.G.;Zhang,J.H.;Burke,T.G.Bioorganic &Medicinal Chemistry 2002,10,103-110.
(4) Hautefaye,P.;Cimetiere,B.;Pierre,A.;Leonce,S.;Hickman,J.;Laine,W.;Bailly,C.;Lavielle,G.Bioorganic & Medicinal Chemistry Letters 2003,13,2731-2735.
(5) Lin,L.Z.;Cordell,G.A.Phytochemistry 1989,28,1295.
(6) Grillet,F.;Baumlov(?),B.;Pr(?)vost,G.;Constant,J.F.;Chaumeron,S.;Bigg,D.C.H.;Greene,A.E.;Kanazawa,A.Bioorganic & Medicinal Chemistry Letters 2008,18,2143-2146.
(7) Org.Syn.Col.Vol.Ⅴ,1973,310.
(8) Tetrahedron Letters 1969,10,3363.
(9) Piancatelli,G.;Scettri,A.;D'Auria,M.Synthesis 1982,1982,245-258.
(10) Czernecki,S.;Georgoulis,C.;Stevens,C.L.;Vijayakumaran,K.Tetrahedron Letters 1985,26,1699-1702.
(11) Lee,T.V.Comprehensive Organic Synthesis 1991,7.
(12) Khuddus,M.A.;Swern,D.J Am Chem Soc 1973,95,8393-8402.
(13) Pfitzner,K.E.;Moffatt,J.G.J.Am.Chem.Soc 1965,87,5661-5670.
(14) Corey,E.J.;Kim,C.U.J.Am.Chem.Soc 1972,94,7586-7587.
(15) Tangirala,R.S.;Antony,S.;Agama,K.;Pommier,Y.;Anderson,B.D.;Bevins,R.;Curran,D.P.Bioorganic & Medicinal Chemistry 2006,14,6202-6212.
(16) 雷英杰 天津理工学院学报 2004,20,106-108.
(17) LaRock,R.;Wiley-VCH Publishers,New York,Weinheim:1999.
(1) 王葆仁;有机合成反应 科学出版社:北京,1985.
(2) Sawada,S.;Nokata,K.I.;Furuta,T.;Yokokura,T.;Miyasaka,T.Chemical & Pharmaceutical Bulletin 1991,39,2574-2580.
(3) Miyasaka,T.;Sawada,S.;Nokata,K.-i.Heterocycles 1981,16,1719-1721.
(4) Lackey,K.;Besterman,J.M.;Fletcher,W.;Leitner,P.;Morton,B.;Sternbach,D.D.Journal of Medicinal Chemistry 1995,38,906-911.
(5) Ashby,E.C.;Park,B.;Patil,G.S.;Gadru,K.;Gurumurthy,R..The Journal of Organic Chemistry 1993,58,424-437.
(6) Lavergne,O.;LesueurGinot,L.;R.odas,F.P.;Bigg,D.C.H.Bioorganic & Medicinal Chemistry Letters 1997,7,2235-2238.
(7) Lavergne,O.;Lesueur-Ginot,L.;Rodas,F.P.;Kasprzyk,P.G.;Pommier,J.;Demarquay,D.;Prevost,G.;Ulibarri,G.;Rolland,A.;Schiano-Liberatore,A.M.;Harnett,J.;Pons,D.;Camara,J.;Bigg,D.C.H.Journal of Medicinal Chemistry 1998,41,5410-5419.
(8) Born,D.;Curran,D.P.;Chavan,A.J.;Kruszewski,S.;Zimmer,S.G.;Fraley,K.A.;Burke,T.G.J.med.Chem 1999,42,3018-3022.
(9) Lavergne,O.;Demarquay,D.;Kasprzyk,P.G.;Bigg,D.C.H.Annals of the New York Academy of Sciences 2000,922,100-111.
(10) Lesueur-Ginot,L.;Demarquay,D.;Kiss,R.;Kasprzyk,P.G.;Dassonneville,L.;Bailly,C.;Camara,J.;Lavergne,O.;Bigg,D.C.H.Cancer Research 1999,59,2939-2943.
(11) Lavergne,O.;Harnett,J.;Rolland,A.;Lanco,C.;Lesueur-Ginot,L.;Demarquay,D.;Huchet,M.;Coulomb,H.;Bigg,D.C.H.Bioorganic & medicinal chemistry letters(Print) 1999,9,2599-2602.
(12) Demarquay,D.;Coulomb,H.;Huchet,M.;Lesueur-Ginot,L.;Camara,J.;Lavergne,O.;Bigg,D.Annals of the New York Academy of Sciences 2000,922,301-302.
(13) Gabarda,A.E.;Du,W.;Isarno,T.;Tangirala,R.S.;Curran,D.P.Tetrahedron 2002,58,6329-6341.
(14) Peters,R.;Althaus,M.;Diolez,C.;Rolland,A.;Manginot,E.;Veyrat,M.The Journal of Organic Chemistry 2006,71,7583-7595.
(15) Arndt,F.;Eistert,B.Berichte der deutschen chemischen Gesellschaft(A and B Series) 1935,68.
(16) Kirmse,W.European Journal Of Organic Chemistry 2002.
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