【作者】 周义宗；

【导师】 江涛；

【作者基本信息】 中国海洋大学 ， 药物化学， 2005， 硕士

【摘要】 本论文共分为三部分,分别为含羧基臂糖-稀土配合物的合成及催化DNA降解研究,糖胺-过渡会属配合物的合成及催化PNPP的活性研究,有机锡羧酸酯的合成及其生物活性研究。 第一部分合成了两个系列的含羧基臂糖-稀土配合物并研究了部分化合物的催化DNA降解的活性。以抗肿瘤活性较好的化合物(5),即(Z)-4-[N-(1’,3’,4’,6’-四-O-苯甲酰基-2’-脱氧-β-D-葡萄糖基)亚氨基]-4-氧代-2-丁烯酸和其类似化合物(6),即邻-(1’,3’,4’,6’-四-O-苯甲酰基-2’-脱氧-2’-氨基甲酰基葡萄糖)-苯甲酸,为配体,分别与La,Nd,Sm,Gd,Dy,Yb的六个稀土氯化物反应,合成了两个系列12个配合物,并通过元素分析,IR,UV,摩尔电导等分析方法研究了配合物的可能结构和配位方式:两类配合物具有类似的配位方式,稀土离子与配体的摩尔比为1:4,配位方式为:配合物中四个配体羧酸中的羧酸根、酰胺羰基和一分子水参与配位,使配合物达到9配位的稳定结构。DNA降解活性显示此类化合物不具有好的降解性能。 第二部合成了三个系列的糖胺-过渡金属配合物,并研究了它们作为水解酶催化水解PNPP的活性。以配位能力较强的氮原子代替糖环上的氧原子合成了三个糖胺化合物,分别为:N,N’-(1-氨基-1-脱氧-β-D-葡萄糖)丙二胺,N,N’-(1-氨基-1-脱氧-β-D-麦芽糖)丙二胺,N,N’,N”-(1-氨基-1-脱氧-β-D-半乳糖)-三-(2-氨乙基)胺。将这三类配体分别与过渡金属Cu(Ⅱ)、Ni(Ⅱ)反应合成了三类6个配合物,并利用元素分析,JR,UV,摩尔电导等分析方法研究了配合物的可能结构,对于Cu(Ⅱ)配合物而言具有扭曲四边形和三角双锥两种配位方式,而Ni(Ⅱ)配合物的构型均为八面体构型。此外我们还研究了配合物作为水解酶催化水解PNPP的活性,结论为:配合物可以显著加速PNPP的水解;在低pH值时Cu(Ⅱ)配合物催化活性较Ni(Ⅱ)配合物的高,但在高pH值时有所下降;而Ni(Ⅱ)配合物的催化活性则随pH的升高而升高。另外,糖上由羟基参与配位的配合物更多还原

【Abstract】 This dissertation were divided into three parts; the first one is the synthesis of rare earth coordinating with saccharide derivatives, the second is the synthesis of saccharide-transition metal complexes and its activity on hydrolysis of PNPP, the third is the synthesis of organotin complexes and its antitumour activity.First, we synthesized two series of sacchride-rare earth complexes and studied their activity on hydrolysis of DNA. We found the compound （5） had good antitumour activity, so we use it and its analogue compound （6） as ligands, react with LaCl₃, NdCl₃, SmCl₃, GdCl₃, DyCl₃, YbCl₃ respectively. Then two series of coordination complexes of rare earth ions were synthesized. The saccharide-rare earth complexes were characterized by elementary analysis, FT-IR, UV spectra and molar conductance and we also speculated the possible structure of the complexes. The two series of complexes have similar structure: Ln:L=1 :4, four coordination oxygen atoms are from carboxyl, four coordination oxygen atoms from acylamide, and the other is from H₂O, the coordination number is nine.We synthesis three series of sacchride-trasition metal complexes and studied their activity on hydrolysis of PNPP. We replaced the oxygen atom of the sugar by nitrogen atom, synthesized the stronger binding carbohydrate ligands. They are N, N’-（1- amino-1-deoxy-β-D-glucose）propane diamine, N, N’-（1-amino-1-deoxy-β-D-maltose） propane diamine, N, N", N"-（1-amino-1-deoxy-β-D-galactose）-triaminotriethyl amine. The ligands reacting with CuCl₂ and NiCl₂ gained six complexes. They were all characterized by elementary analysis. FT-IR. UV spectra and molar conductance and we also speculated the possible structure of the complexes. We studied the catalytic activities of glycosylamine-metal complexes on hydrolysis of picolinate. and found that hydrolysis is significantly accelerated in the presence ofcomplexes over spontaneous hydrolysis. In low pH the Cu（ll） complexes have higher activity, but it is lower when pH is higher. While the Ni（ll） complexes is on the contrary. We also find that when the OH group of the sugar coordination with the metal the hydrolysis activity is higher. So we can decide that the OH group of the sugar play important role in the hydrolysis.Dibutyltin（ IV） oxide complex reacts with the cantharidin analogue. 4’-（7-oxabicyclo[2,2,l]-5-heptane-2,3-dicarboximide） benzoic acid and a-（7-oxabicyclo[2,2,l]-5-heptane-2,3-dicarboximide） acetic acid to give the complexes [（p-C8H8NO3-C6H4-COOBu2Sn）2O]2（29）, （p-C8H8NO3-C6H4-COO）2SnBu2 （30） and （a-C8H8NO3-CH2-COO）2SnBu2 （31） which have been characterized by IR, ’H NMR, 13C NMR and 119Sn NMR. Single x-ray crystal structure analysis has been determined for the compound 29, which was analogue to most other [（RCOOBu2Sn）2O]2. The dimer features central of Bu4Sn2O2 unit with the two Bu2Sn groups being linked via bridging oxygen atom. Each tin atom adopts distorted trigonal bipyramides via two carbons from a dibutyl moiety and three oxygen atoms from cantharidin analogue and bridging oxygen. In vitro test shows compound 29-31 exhibit high cytotoxicity against P388 and HL-60, but it is lower against A-549. The effects of compounds 29-31 have been tested on human hematopoietic progenitors using clonogenic effect. Cytotoxic concentration and no effect dose concentration have been determined after scoring colonies derived from hematopoietic progenitors incubated 14 days. Results show that compound 29 is less myelotoxic than compound 30 and 31 according cytotoxic and no effect doses.更多还原