86 中国药物化学杂志 第12卷 [33 Bringmann G, Ledermann A, Francois G. Dimeric [36 Wu CC, Ko FN, Wu TS, et al. Antiplatelet effects of murrayafoline2A, a potential biscarbazole alkaloid clausineD isolated from Clausen excavata [J] biomimetic" synthesis, atropisomer separation, and Biochim Biophys Acta, 1994, 1201(1): 1-6 antimalarial activity [J]. Heterocycles, 1995, 40(1) 37 Chaichantipyuth C, Pummangura S, Naowsarn K, et 293-300 al. Two new bioactive carbazole al kaloids from the [34] Joshi BS, Kamat DH, Gawad DH, et al. Structure and root bark of Clausena harmandiana[J]. J Nat Prod synthesis of heptaphylline [J]. Phytochemistry 1988,51(6):1285-1288 1972,11(3):2065-207 [38 Chavi Y, Somkrit S, Prachack S, et al. Coumarins and 35] Narasimhan NS, Paradkar MV, Gokhale AM. Synthe2 carbazoles with antiplasmodial activity from clausena ses of grinimbine. mahanimbine isomahanimbine harmandiana[J ]. Planta Med, 2000, 66(3): 2 ]. Indian J Chem,1976,14B:329-331 Research progress on plant al kaloids of gen us Clusena YAN Shao2yu',2, CUI Cheng2bin',, YAO Xin2sheng (11 Tianjin Institute for Biomedicinal Research TIBiR), Tianjin 300384, China 21 School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China 31 Marine Drug and Food Institute, Ocean University of Qingdao, Qingdao 266003, China) Abstract: Species of genus Clusena possess widespread pharmaceutical activities and a lot of research works had been done on chemical constit uents and biological activities of the genus Clusena. The recent research progress on plant alkaloids from the genus Clusena was reviewed in the present paper in view of the struc2 tures, isolation, structure elucidation, synt hesis met hods and biological activities Key words Rutaceae; Clusena; alkaloid (上接第165页) An improved synthesis of zoledron ic acid as a ne w treating hypercalcemia drug LIJia2ming, TONG Yuanfeng, ZHANG Yong (1I Dept. of Pharmaceutical Chemistry, A nhui College of Traditional Chinese Medicine Hefei 230038, China 21 Hefei Instant Pharmaceutical Institute, Hefei 230031, China) Abstract Zoledronic acid, a new drug for treating hypercalcemia, was synthesized by the condensation of im2 idazole with ethyl bromoacetate, hydrolysis to afford imidazole2 12ylacetic acid, and then reacted with phos2 phorous acid and phosphorus trichloride to give the target product, the overall yield was 2710%. In this pa2 per we used TEBA instead of BBDE Cl as phase transfer catalyst and imidazole acetic acid instead of its hy2 drochloride salt as the key intermediate, this process can easily obtain the product in good quality and yield Key words zoledronic acid ; hypercalcemia; synt hesis o1995-2005 Tsinghua Tongfang Optical Disc Co, Ltd. Al rights reserved.[33 ] Bringmann G , Ledermann A , Francois G. Dimeric murrayafoline2A , a potential bis2carbazole alkaloid : “biomimetic”synthesis ,atropoisomer separation ,and antimalarial activity [J ]. Heterocycles ,1995 ,40 (1) : 293 - 300. [34 ] Joshi BS , Kamat DH , Gawad DH ,et al. Structure and synthesis of heptaphylline [ J ]. Phytochemistry , 1972 ,11 (3) :2065 - 2071. [35 ] Narasimhan NS ,Paradkar MV , Gokhale AM. Synthe2 ses of grinimbine , mahanimbine & isomahanimbine [J ]. Indian J Chem ,1976 ,14B :329 - 331. [36 ] Wu CC , Ko FN ,Wu TS ,et al. Antiplatelet effects of clausine2D isolated from Clausens excavata [ J ]. Biochim Biophys Acta ,1994 ,1201(1) :1 - 6. [37 ] Chaichantipyuth C , Pummangura S ,Naowsarn K , et al. Two new bioactive carbazole alkaloids from the root bark of Clausena harm andiana[J ].J Nat Prod , 1988 ,51 (6) :1285 - 1288. [ 38 ] Chavi Y ,Somkrit S ,Prachack S ,et al. Coumarins and carbazoles with antiplasmodial activity from Clausena harm andiana[J ]. Planta Med ,2000 ,66 (3) : 277 - 279. Research progress on plant alkaloids of genus Clusena YAN Shao2yu 1 ,2 ,CU I Cheng2bin1 ,3 , YAO Xin2sheng 2 (11 Tianjin Instit ute f or B iomedicinal Research ( TIB i R) , Tianjin 300384 , China ; 21 School of T raditional Chinese M ateria Medica , S henyang Pharm aceutical U niversity , S henyang 110016 , China ; 31 M arine Drug and Food Instit ute , Ocean U niversity of Qingdao , Qingdao 266003 , China) Abstract :Species of genus Cl usena possess widespread pharmaceutical activities and a lot of research works had been done on chemical constituents and biological activities of the genus Cl usena. The recent research progress on plant alkaloids from the genus Cl usena was reviewed in the present paper in view of the struc2 tures ,isolation ,structure elucidation ,synthesis methods ,and biological activities. Key words :Rutaceae ; Cl usena ;alkaloid (上接第 165 页) An improved synthesis of zoledronic acid as a ne w treating hypercalcemia drug L I Jia2ming 1 , TON G Yuan2feng 2 ,ZHAN G Yong 2 (11 Dept . of Pharm aceutical Chemist ry , A nhui College of T raditional Chinese Medicine , Hef ei 230038 , China ; 21 Hef ei Instant Pharm aceutical Instit ute , Hef ei 230031 , China) Abstract :Zoledronic acid ,a new drug for treating hypercalcemia ,was synthesized by the condensation of im2 idazole with ethyl bromoacetate ,hydrolysis to afford imidazole212ylacetic acid ,and then reacted with phos2 phorous acid and phosphorus trichloride to give the target product ,the overall yield was 2710 %. In this pa2 per ,we used TEBA instead of BBDE Cl as phase transfer catalyst ,and imidazole acetic acid instead of its hy2 drochloride salt as the key intermediate ,this process can easily obtain the product in good quality and yield. Key words :zoledronic acid ;hypercalcemia ;synthesis 681 中 国 药 物 化 学 杂 志 第 12 卷 © 1995-2005 Tsinghua Tongfang Optical Disc Co., Ltd. All rights reserved