~3H和~(14)C标记常咯啉的合成

本文合成了抗心律失常新药常咯啉的~3H和~(14)C标记化合物。5-溴邻氨基苯甲酸按常咯啉类似合成方法经四步反应生成6-溴代常咯啉(Ⅰ),Ⅰ在钯碳催化下通氚制得[6-~3H]-常咯啉(Ⅱ)。[~(14)C]-甲酸铵脱水得[~(14)C]-甲酰胺后经三步反应制得[2-~(14)C]-常咯啉(Ⅲ)。4-(对羟     

[~(14)C]-氯硝柳胺、[~(14)C]-六氯对二甲苯和[~(35)S]-硫溴酚的制备

2-甲氧基-5-氯苯胺与K~(14)CN经Sandmeyer反应制成2-中氧基-5-氯苯甲腈经水解得5-氯-[1-~(14)C]-水杨酸,后者制成相应的酰氯后与2-氯-4-硝基苯胺反应即得[~(14)C]-氯硝柳胺,总收率38％。对-甲苯胺与K~(14)CN经Sandmeyer反应生成的腈经水解后得[1-~(14)C]-对甲苯甲酸,后者用LiAlH_4还原成[1-~(14)C]-对甲苯甲醇,再以SoCl_2氯化成相应的氯苄,进一步通氯即得[~(14)C]-     

用~(14)C和~(15)N标记常咯啉研究药物代谢

常咯啉即2,6-双(1-吡咯烷基)-4-(4-喹唑基胺基苯酚),是新型抗心律不齐药。长期服用后有肤色变深、GPT上升等副作用。为寻找产生副作用的原因及进一步从药物代谢途径中寻找更有效的抗心律不齐药的信息,研究其在体内的代谢就成了十分必要而有意义的工作,本文用[~(14)C]常咯啉和[~(15)N]常咯啉的方法研究其在体内的代谢情况。     

[15—~(14)C]双氢青蒿内酯的合成

4-羰基-4-去甲四氢青蒿酸甲酯(3)与~(14)CH_3MgI起格氏反应得[~(14)C]4-羟基四氢青蒿酸甲酯(4α),4α经脱水和水解反应得[~(14)C]二氢青蒿酸(5α)和它的异构物(6α)的混合物,用四氧化锇和N-甲基吗琳N-氧化物氧化即得[15-~(14)C]双氢青蒿内酯(2α)和另一产物[15-~(14)C]3,4-二羟基四氢青蒿酸(7α);还同时合成了相应的~(13)C和氘标记化合物(2b,c)和(7b,c)。     

[~(14)C]标记丙双吗啉(AT-2153、MST-02)的合成

丙双吗啉(AT-2153,MST-02),化学名为1,2-双(4-吗啉甲撑)-3,5-二氧哌嗪基丙烷,对多种肿瘤有较好的抑制作用。为了研究其在体内的过程,本文合成了哌嗪环~(14)C标记的西双吗啉(I_α)和甲撑~(14)C标记的乙双吗啉(I_b)。[1-~14C]乙酸经溴化成[1-~(14)C]溴乙酸(Ⅱ),Ⅱ与1,2-丙二胺作用生成1,2-丙二胺四乙酸[羰-~(14)C](Ⅲ)。Ⅲ与甲酰胺加热生成[羰~(14)C]1,2双(3、5-二氧哌唪)丙烷(Ⅳ),Ⅳ与甲醛和吗啉起Mannich反应即得I_α,收率43.4％,比放射性26.3MBq/mmol。将Ⅳ与[~(14)C]甲醛和吗啉反应则得I_b,收率75％,比放射性34.4MBq/mmol,冷试验分析H-NMR谱I_a、I_b与标准相同,元素分析与计算值相符。     

~(14)C标记双炔失碳酯、双二氯乙酰辛二胺的合成

双炔失碳酯、1,8-双二氯乙酰辛二胺(又称Win 18446)是两种避孕药物,前者为女用避孕药,后者能抑制生精过程,是有希望的男性抗生育药物。为了研究它们在体内的吸收分布和代谢以指导合理用药。我们合成了它们的~(14)C-标记化合物。双炔失碳酯(Ⅰ)的标记其合成路线基本与非标记合成相似,但操作上作了适当改进。所用乙炔-~(14)C_2,是用碳酸钡-~(14)C(0.5g,5mCi)按文献方法制备。 我们用1,6-二溴己烷与氰化钾-~(14)C作用成相应的二腈化合物(Ⅴ),经还原成1,8-二氨基辛烷-1,8-~(14)C_2(Ⅵ),再与二氯乙酸乙酯反应即得~(14)C-标记的Ⅱ。反应式如下:     

[2′,6′-~3H]除草醚和[2′,6′-~3H]草枯醚的合成

用合成法制备了[2’,6’-~3H]除草醚和[2’,6’-~3H]草枯醚。以间溴氯苯(Ⅰ)为起始原料,经催化卤-氚取代反应制得[3,5-~3H]氯苯(Ⅱ);然后用硝酸-浓硫酸的混合物硝化(Ⅱ)得[3,5-~3H]对氯硝基苯(Ⅲ);最后使(Ⅲ)分别与2,4-二氯苯酚或2,4,6-三氯苯酚起缩合反应生成[2’,6’-~3H]除草醚(Ⅳ)和[2’,6’-~3H]草枯醚(Ⅴ),比活度分别为1.16TBq/mol和1.89TBq/mol,放化纯度均大于95％。     

植物生长延缓剂~(14)C-PP333的合成

用相转移催化方法,标记合成了1-对氯苯基-2-[(5-~(14)C)-1,2,4-王唑-1-基]-4,4-二甲戊-3-醇(~(14)-PP333)。其步骤包括:在相转移催化剂(PEG800)的存在下,(5-~(14)C)-1,2,4-三唑与一氯片呐酮在乙酸乙酯溶液中反应,生成(5-~(14)C)-α-三唑基片呐酮(2);后者在苯溶液中再与对氯氯苄反应,生成~(14)C-三唑酮(3);最后在甲醇溶液中~(14)C-三唑酮用硼氢化钠还原得到~(14)C-PP333,其总放化收率为20.9％(以~(14)C-三唑计),放化纯度大于99％。     

~(14)C-~3H双标记炔诺酮庚酸酯的合成

炔诺酮庚酸酯是一种长效避孕药。为了研究该药在体内的吸收分布、代谢过程和作用机制,我们合成了~(14)C-~3H双标记炔诺酮庚酸酯。首先制备了炔诺酮-6,7-~3H和庚酸钠-1-~(14)C。前者系用19-去甲基-Δ~(4.6)-雄烯-3,17-二酮为原料,通过钯-碳酸钙催化氚化,用炔锂乙二胺络合物炔化制得。后者用格氏反应制得。然后两者分别进一步酯化成炔诺酮-6,7-~3H庚酸酯与炔诺酮庚酸酯-1′-~(14)C,并按一定比例相互混合成双标记分子。     

氮肥增效剂2-氯-6-[三氯甲基-~(14)C]吡啶的制备

2-氯-6-[三氯甲基]-吡啶[商品名称 N-Serve,代号 CP],是一种抑制铵态氮的硝化,减少氮的流失,从而提高氮肥利用率的化学药剂(以下简称 CP)。应用 CP-~(14)C 可以研究 CP 及其降解产物在植物和土壤中的残留动态。1964年雷德曼(C.T.Redemann)等人曾报导了 CP-~(14)C 的合成方法。我们对雷德曼等人的方法进行了改进,即以2-溴吡啶为原料,与正丁基锂作用,经~(14)CO_2羧化得[羧基-~(14)C]-吡啶羧酸-2,再用五氯化磷在200℃下进行氯化反应得 CP-~(14)C。这个方法原料来源方便,操作比较简单。     

高压反相液相色谱法分析[~3H]CAMP与[~3M]CGMP

CAMP(环磷酸腺苷)和CGMP(环磷酸鸟苷)属环核苷酸类,,在机体中的含量极低,约为每mg湿组织pg分子水平,用一般的分析方法不能测定。主要采用竞争性蛋白质结合分析法、放射免疫法和薄层色谱法进行分析。近年来,用高压液相色谱分离分析环核苷酸,定量方便、分析速度快、检测装置灵敏度高,具有其他分析方法所没有的优点。过去,对环核苷酸的分离都在离子交换柱上进行,最近,Krstulovic等采用反相色谱,在μBondapak C_(18)柱上进行分离分析,不需对样品进行预浓缩,使方法更为简便,而且柱寿命长。[~3H]CAMP是竞争性蛋白质结合分析法测定环磷酸腺苷,以及[~3H]CGMP是放射免疫法测定环磷酸鸟苷所必不可少的试剂,它们的放化纯将直接影响这两种分析方法的成败。本工作采用高压反相分配色谱法,在ODS术上,用甲醇-20 mmol/l KH_2PO_4作流动     

电位滴定法研究~(99)Tc-HMDP和~(99)Tc-HEDP中Tc的氧化态

~(99)Tc-HMDP和~(99)Tc-HEDP溶液是在相应的螫合剂存在下,用过量SnCl_2还原~(99)TcO_4-制得。用标准I_2液对SnCl_2进行了剩余量电位滴定,确定了在pH～3的介质中,~(99)Tc-HMDP和~(99)Tc-HE-DP中~(99)Tc的氧化态均为+4。全部实验在N_2气流中进行。~(99)Tc-HMDP和~(99)Tc-HEDP的紫外光谱表明:在用I_2滴定的过程中,~(99)Tc只处于一种氧化态+4;将它们放置在空气中,一小时后仍较稳定。     

Equilibrium and kinetic studies of selective adsorption and separation for strontium using DtBuCH18C6 loaded resin

A crown ether loaded resin was prepared by successive impregnation and fixing the 4′,4′(5″)-di(tert-butylcyclohexano)-18-crown-6 (DtBuCH18C6) and its molecule modifier, 1-dodecanol, onto the porous silica/polymer composite support (SiO₂-P particles). The characterization of DtBuCH18C6 loaded resin was examined by thermal gravimetry and differential thermal analysis and electron probe microanalysis. The adsorption behavior of Sr(II), Cs(I), Ru(III), Pd(II), La(III), Nd(III), Sm(III), Gd(III), Zr(IV), and Mo(VI) was investigated by the batch method. Furthermore, the column test for Sr (II) was performed. The batch experiments were carried out by varying the shaking times, HNO₃ concentration, and initial concentration of metal ions. A relatively large K _d value above 182 cm³/g for Sr(II) was obtained in the presence of 3 M HNO₃. In contrast, the K _d values of Cs(I), Ru(III), Pd(II), La(III), Nd(III), Sm(III), Gd(III), Zr(IV), and Mo(VI) were considerably lower than 10 cm³/g. The adsorption of Sr(II) was found to be controlled by chemisorption mechanism, and followed a Langmuir-type adsorption equation. The breakthrough curve of Sr(II) had S-shaped profile, and the elution percentage was estimated to be 99.9% by using the eluent of H₂O.     

~(101)Tc半衰期的测量

在微型中子源反应堆中辐照75 mg仲钼酸铵20 min,冷却12 min,然后用α-安息香肟-乙酸乙酯在水相介质为0.8 mol/L HNO3、相比1∶1条件下,连续萃取2次分离出了无载体、放化纯的~(101)Tc样品.用HPGe γ探测器对306.8 keV γ射线采用位置接续法跟踪测量,分别用"平移法"、"迭代法"和"R-值法"进行数据处理,得到~(101)Tc的半衰期为(14.02±0.01) min(n=5),经检验数据可靠.     

^14C标记农药杀螟松和马拉硫磷的制备

以Ｂａ＾１４ＣＯ３为起始原料制得＾１４ＣＨ３ＯＨ，然后和＾１４ＣＨ３ＯＨ与ＰＳＣｌ３在碱性条件下反应，再加入甲基砂基苯酚，在甲基异丁酮溶剂体系下制得＾１４Ｃ－刹螟松，放化纯度〉９５％，放射性比活度为１８８．７ＢＭｑ／ｍｏｌ，＾１４ＣＨ２ＯＨ与Ｐ２Ｓ５合成的中间体，加顺丁烯酸二乙酯在甲苯溶剂体系中反应制成＾１４Ｃ－马拉硫磷，放化纯度〉９５％，放射性比活度为１５６．４ＭＢｑ／ｍｏｌ。     

放射性脑功能显像剂~*I-IMP的合成

合成了碘-125标记、N-异丙基-对-碘安非它命作为脑灌注显像剂。N-异内基-对-碘安非它命的合成路线包括下列步骤:酰化、碘化、水解、烷基化。~(125)I-IMP标记化合物通过加入Na~(125)I可到含有前体化合物、Cu(NO_3)_2和SnCl_2·2H_2O的小瓶中制备,其标记率大于95%。经纯化后,纯度通过二种溶剂系统测定,其放化纯度大于98%。     

CATALYTIC LABELLING AND ~3H NMR ANALYSES OF SOME AROMATIC AND HETEROCYCLIC COMPOUNDS

This paper described the ~3H NMR determination of the positions and content of 24 tritium labeled aromatic and heterocyclic compounds prepared by catalytic tritiation derivatives, pyrrole, 1,2,4-triazole, thiazole, benzothiazole, purine and derivatives, indole, indanol, piperidine and derivative, diphenylamine, N- phenylanthranilic acid, 8- OH- quinoline, naphthol, diphenylether have been tritiated by catalytic exchange method using tritiated water and platinum catalyst (from the dioxide and sodium borohydride), and the pattern of labelling has been assigned by ~3H NMR spectroscopy. The results show that this exchange process can give general labelling compounds at various time and temperatures. For 4-Br-diphenylether, Raney nickel was used instead of Pt as a catalyst.     

HTR-PM中~(14)C产生与释放行为研究

~(14)C具有较长的半衰期,可与稳定同位素一起进入生物圈,从而在核电站的环境影响评价中受到关注.本文基于HTR-PM给出了产生~(14)C的各反应模型,并代以HTR-PM参数,对HTR-PM中~(14)C的年产生量和气态释放量作出估算.最后,将计算结果与CANDU堆型进行了比较.     

Comparison of Four Bidentate Phosphoric and Diamide Compounds for the Extractability of Actinides

Using four bidentate phosphonate and diamide ligands (L), the extraction of Am(III), Th(IV), Np(V) and U(VI) was studied and their extraction species and extractability in these extractants were discussed. The extractant containing the phosphoric oxygen has stronger chelation than that with the carbonyl oxygen atoms. The molar ratios in the main chemical forms extracted are 1:3 for Am:L, 1:1 for Th:L and Np:L and 1:2 for U:L from the relationship between log D(An) and log[L]. The order of D in actinides with the different oxidation states is U(VI)>Th(IV)> Am(III)>Np(V), which shows the different order from that for HDEHP and HTTA, namely Th(IV)>U(VI)> Am(III)>Np(V). It is clear that BDPPM, a diphosphoric dioxide extractant, has high extractability towards all An used here.     

Solvent Extraction of Np (V) with CMPO from Nitric Acid Solutions Containing U (VI)

The extraction of Np(V) in the presence of U(VI) or Nd(III) was studied with 0.2 M CMPO- decalin and with 0.2 M CMPO-1.4 M TBP-n-dodecane. Distribution ratios of Np(V) decreased with increasing the concentration of Nd(III), which was considered to be explained by the decrease in the concentration of free CMPO. On the other hand, distribution ratios increased as the concentration of U(VI) increased. The absorption spectrum of Np(V) in organic solution showed a new absorption peak which was probably attributable to the formation of cation-cation complexes of Np(V) and U(VI). Assuming the formation of cation-cation complexes, the dependence of distribution ratio of Np(V) on the concentration of U(VI) was found to be semi-quantitatively explained.