雌甾-卟啉仿酶模型化合物的合成、构型与反应性

17β-雌二醇与氯乙酰氯反应所得产物2与卟啉1反应, 合成了雌甾-双卟啉二聚体3及雌甾单卟啉4。引入金属后得到雌甾-卟啉钴仿酶模型化合物3a及4a。它们的结构与构型经UV-Vis,IR, 1H NMR和元素分析确证, 并考查了3a对氢醌氧化反应的催化性能。     

含磷杂环化合物的研究——Ⅱ.1,3,2-苯并二氧磷杂戊环衍生物

本文合成了七个2,2-二硫代-1,3,2-苯并二氧磷杂戊环的叔胺盐1a～g,并用两种方法制得六个2,2-取代-1,3,2-苯并二氧磷杂戊环化合物2a～c和3a～c。除1a外的所有化合物均为新化合物,对它们的结构进行了初步解析。     

2-芳基-5-(6-哒嗪酮-3-基)-1,3,4-噁二唑的合成

1,4,5,6-四氢-6-哒嗪酮-3-甲酰肼(1)和1,6-二氢-6-哒嗪酮-3-甲酰肼(2)与芳香醛反应得到相应的芳香醛腙3a～3g和5a～5g, 再将3a～3g, 5a～5g在溴的作用下, 合环得到一系列1,3,4-噁二唑的衍生物4a～4g和6a～6g. 化合物的结构经1H NMR, IR, MS和元素分析得以证实.     

甾体-卟啉化学的研究

通过雌甾-卟啉的键链, 合成了四个卟啉-甾体化合物. 并用紫外、核磁、红外和元素分析鉴定了它们的结构. 并用差热分析证明它们各含一分子结晶水.     

含羧基或酯基的N-甲基异噁唑啉盐的合成及其对细胞分裂周期25B磷酸酯酶和蛋白酪氨酸磷酸酶1的体外抗癌活性

以硫酸二甲酯作为N-甲基化试剂,与相应的异噁唑啉1a～1g或3a～3g反应,并在盐酸中以三氯化铁作为阴离子交换试剂,合成了14个未见文献报道的2-甲基-3-乙氧基羰基-5-芳基-3a,6a-二氢-4,6-二氧代氮杂茂并[3',4'-d]异噁唑四氯化铁酸盐衍生物2a～2g和2-甲基-3-羧基-5-芳基-3a,6a-二氢-4,6-二氧代氮杂茂并[3',4'-d]异噁唑四氯化铁酸盐衍生物4a～4g,其结构经~1H NMR,IR和元素分析确证,并进行了初步药物活性筛选.化合物2和4显示了不同程度的抗癌活性.体外抗癌活性试验表明,当样品浓度为20μg/m L时,化合物2a～2g和4a～4g对细胞分裂周期25B磷酸酯酶(Cdc25B)的抑制率分别在97.32%～99.94%之间和97.45%～99.92%之间.化合物2a～2g和4d～4g对含SH2结构域蛋白酪氨酸磷酸酯酶-1(SHP1)具有良好的抑制活性,其抑制率分别在52.18%～97.15%和86.66%～99.45%之间.只有4a～4c的抑制率在15.21%～47.11%之间(IC500.5μmol/L).在此基础上,初步讨论了该类化合物的构效关系.     

新型吡啶卟啉-蒽醌磺酰丙胺季铵盐的合成

设计合成一些能作为结构探针和化学治疗剂的核酸断裂剂为不同学科背景的研究者涉足分子生物学领域提出的挑战之一.天然生物酶在许多研究领域具有重要的作用,但由于它们自身特性的局限性,使它们的普及应用受到了限制.而今,合成具有高度序列选择性的核酸断裂剂成为人们研究的重点[1,2].卟啉和蒽醌类化合物均为有效的核酸定位断裂剂,利用它们各自特征来合成新型的核酸断裂剂,引起分子生物学,抗癌和抗病毒领域的研究者的极大关注.为深入探讨此类化合物在DNA断裂中的作用,我们合成了两种未见文献报道的卟啉-蒽醌季铵盐化合物(产率20%～25%)和两种卟啉-丙胺季铵盐化合物(产率10%～12%),对它们进行了UV,IR,1H NMR,MS及荧光性质的研究和表征.     

4-芳亚甲基-2-羟基-3-蒎酮类化合物的合成及其紫外吸收特征研究

以(-)-α-蒎烯为原料合成了系列新型4-芳亚甲基-2-羟基-3-蒎酮类化合物.(-)-α-蒎烯经选择性氧化得到(+)-2-羟基-3-蒎酮;在碱催化作用下,(+)-2-羟基-3-蒎酮与苯甲醛、对甲基苯甲醛、对甲氧基苯甲醛、对羟基苯甲醛、对氯苯甲醛、对硝基苯甲醛和糠醛等芳香醛缩合,得到系列光学活性4-芳亚甲基-2-羟基-3-蒎酮类化合物a～g.采用1H NMR,13C NMR,GC-MS和FT-IR等分析手段对合成所得4-芳亚甲基-2-羟基-3-蒎酮类化合物的结构进行了表征,考察了它们的紫外吸收特性及光稳定性.结果表明,化合物a,b,e对UVB具有良好的吸收性能;而化合物c,d,f,g兼具长波紫外线(UVA)和中波紫外线(UVB)的吸收性能.化合物a～g的光稳定性顺序为d>c>e>f>b>a>g.     

杯芳烃-卟啉化合物及其金属配合物的Langmuir-Blodgett膜研究

通过对杯芳烃-卟啉化合物及其锌、钯配合物LB膜的表面压-表面积等温线、紫外可见光谱和傅里叶变换红外光谱的检测,研究了它们在气/液界面和Langmuir-Blodgett膜中的性质,并用量子力学方法优化了杯芳烃-卟啉化合物的构型.结果表明,成膜时3种化合物分子中卟啉环都倾斜地排列在亚相表面,且卟啉环间存在π-π相互作用.连接杯芳烃和卟啉之间的碳氢链在膜性质中起着重要的作用,杯芳烃-卟啉化合物分子中这种碳氢链的有序性小于其锌、钯配合物分子中的这种碳氢链有序性.     

间氯苯基锰卟啉-5-氟尿嘧啶配合物的合成及其对癌细胞的抑制活性

合成了4种新5-氟尿嘧啶-卟啉衍生物：5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]-10,15,20-三(3-氯苯基)卟啉(1a)、5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]- 10,15,20-三(3-氯苯基)锰卟啉(2a)、5-[3-(3-(5-氟尿嘧啶-1-基)丙氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2b)和5-[3-(4-(5-氟尿嘧啶-1-基)丁氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2c),通过UV-Vis、IR、MS及元素分析表征了它们的结构。 用噻唑蓝法（MTT法）测定了化合物2a、2b和2c对人胃癌细胞株BGC-823的抑制活性。 化合物2b的半数抑制浓度IC50为1.34 μmol/L,表明有一定的细胞毒作用。     

新型桥连双卟啉化合物的合成及结构表征

通过将4,4′-二羧基-2,2′-联吡啶、2,6-二溴甲基吡啶、2,6-二羟甲基吡啶和1,8-二氨基萘分别与5-(4-羟基苯基)-10,15,20-三苯基卟啉(1a)、5-(4-甲酰苯基)-10,15,20-三苯基卟啉(1b)和5-[4-(4′-溴代丁氧基)苯基]-10,15,20-三苯基卟啉(1c)反应,合成了3类新型的双卟啉化合物2a-2e,经IR,¹HNMR,MS,UV-Vis光谱及元素分析对中间体和目标化合物的结构进行了表征.     

Asymmetric syntheses of 1-aryl-2,2,2-trifluoroethylamines via diastereoselective 1,2-addition of arylmetals to 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide

Condensation of N-tert-butanesulfinamide (S)-1 with trifluoroacetaldehyde hydrate 2a afforded 2-methyl-N-(2,2,2-trifluoroethylidene)propane-2-sulfinamide 3. Without isolation and purification, imine 3 was added to various aryllithium reagents to give highly diastereomerically enriched adducts 5a-g. Acidic methanolysis of 5a-g provided the desired 1-aryl-2,2,2-trifluoroethylamine hydrochloride compounds 6a-g. [reaction: see text].     

Haloacetylated enol ethers. 7 . Synthesis of 3-aryl-5-trihalomethylisoxazoles and 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles

β-Aryl-β-methoxyvinyl trihalomethyl ketones 1a-g, 2a-g [aryl = p-YC₆H₄ where Y= H, Me, OMe, F, Cl, Br, NO₂] are cyclocondensed with hydroxylamine hydrochloride to afford the 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles 3a-g, 4a-f in good yield. The dehydratation of compounds 3a-g with concentrated sulfuric acid, led the corresponding 3-aryl-5-trichloromethylisoxazoles 5a-g . An alternative one-pot procedure yields 3-aryl-5-trihalomethylisoxazoles 5,6a-g directly by cyclocondesation of 1,2a-g with hydroxylamine hydrochloride in the presence of an excess of concentrated hydrochloric acid.     

Synthesis, acidity and antioxidant properties of some novel 3,4-disubstituted-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives

3-Alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones 2a-g reacted with 4-diethylaminobenzaldehyde to afford the corresponding 3-alkyl(aryl)-4-(4-diethyl-aminobenzylidenamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones 3a-g. The acetylation reactions of compounds 3a-e were investigated and compounds 4a-e were thus obtained. The new compounds were characterized using IR, (1)H-NMR, (13)C-NMR, UV and MS spectral data. In addition, the newly synthesized compounds 3a-g were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents such as isopropyl alcohol, tert-butyl alcohol, acetone and N,N-dimethylformamide (DMF), and the half-neutralization potential values and the corresponding pKa values were determined for all cases. Moreover, 3 and 4 type compounds were also screened for their antioxidant activities.     

Formation and characterization of a multicomponent equilibrium system derived from cis- and trans-1-aminomethylcyclohexane-1,2-diol

Both cis and trans isomers of amino diols 3-6 were prepared stereoselectively. In the reactions between 3-6 and phenyl isothiocyanate, the ring closure proceeded regioselectively and resulted only in spiro derivatives of 2-phenyliminooxazolidines 9, 10, 13, and 14. The reaction of cis- (or trans-)1-aminomethylcyclohexane-1,2-diol 4 (or 6) with 1 equiv of an aromatic aldehyde 15a-g in EtOH at room temperature resulted in a complex, multicomponent equilibrium mixture of 16a-g and 18a-g (or 17a-g and 19a-g), in each case consisting of a five-component, ring-chain tautomeric system 16A-E (or 17A-E), involving the Schiff base, two epimeric spirooxazolidines, two epimeric condensed 1,3-oxazines, and some of the four tricyclic compounds 18A-D (or 19A-D). The five-component, ring-chain equilibria were found to be adequately described by the Hammett-Brown linear free energy equation.     

Reductive ring cleavage of 1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones with raney-nickel alloy. Synthesis of N-benzoyl-3-alkylamino-3-phenylalanine amides from rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone

rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone ( 1 ) was alkylated at position 1 with carbonyl compounds 2a-g . The corresponding rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone-1-azomethine imines 3a-g , were treated with sodium borohydride to give rel-(4R,5R)-1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones 4a-g . Reduction of pyrazolidinones 4a-g with Raney-nickel alloy in methanolic potassium hydroxide furnished rel-(4R,5R)-N-benzoyl-3-alkylamino-3-phenylalanine amides 5a-f .     

13C-NMR study on the tautomerism of 3-(arylhydrazono)methyl-2-oxo-1,2-dihydroquinoxalines between the hydrazone imine and diazenylenamine forms

The ¹³C-nmr study was carried out for the tautomerism of the 3-(arylhydrazono)methyl-2-oxo-1,2-dihy-droquinoxalines 1a-g and 2a-e between the hydrazone imine A and diazenylenamine B forms, providing the carbon chemical shifts for the tautomers A and B of compounds 1a-g and 2a-e. The comparison of the carbon chemical shifts for the tautomer B of compounds 1d, 1f , and 2b in deuteriodimethyl sulfoxide with those in deuteriotrifluoroacetic acid showed that the C_4a, C₅, and diazenyl carbons were considerably shielded presumably due to the azo N-deuteration in deuteriotrifluoroacetic acid.     

General synthetic entry to linearly-fused dihydrobenzocyclobutene-1,2-diones and benzocyclobutene-1,2-diones via annulation of 1,2-bis(methylene)carbocycles with 3-chloro-3-cyclobutene-1,2-dione

The tandem Diels-Alder/dehydrochlorination reaction of semisquaric chloride (1) with the 1,2-bis(methylene)cycloalkanes 2a-c and 1,2-bis(methylene)-4-cyclohexene (9) affords the linearly-fused cycloalkanodihydrobenzocyclobutene-1,2-diones 3a-c and 3,4,7,8-tetrahydrocyclobuta[b]-naphthalene-1,2-dione (10), respectively. On treatment with MnO2, 3a-c are dehydrogenated to the respective carbocycle-fused benzocyclobutene-1,2-diones 4a-c in good yields. 3a and 3b react with bromine to give the addition products 5a,b, which, on treatment with silver trifluoroacetate, afford the benzocyclobutene-1,2-diones 4a,b. For preparative purposes, the sequence 3-->5-->4 can be performed advantageously as a "one-pot procedure". Double-condensation reactions of 4a,b with alpha,alpha'-biscyano-o-xylene and o-phenylenediamine afford the pentacyclic biphenylenes 7a,b and the cyclobutahetarenes 8a,b, respectively. These cyclobutenediones suggest themselves as building blocks for the construction of extended linearly-fused polycyclic compounds with novel ring sequences. o-Quinodimethanes 12a-g generated in situ by the thermal decomposition of the respective 1,4-dihydro-2,3-benzoxathiin-3-oxides (sultines) 11a-g react with semisquaric chloride (1) to afford the 3,8-dihydronaphtho[b]cyclobutene-1,2-diones 13a-g. These, on dehydrogenation with bromine and/or MnO2, furnish the naphtho[b]cyclobutene-1,2-diones 14a-g in fair to good yields. As described for 4a,b the naphtho[b]cyclobutene-1,2-diones 14a-c are condensed with alpha,alpha'-biscyano-o-xylene and o-phenylenediamine to furnish the pentacyclic biphenylenes 15a-c and the pentacyclic cyclobutahetarenes 16a-c.     

5-Oxo-1,4-dihydroindenopyridines: Calcium modulators with partial calcium agonistic activity

The title compounds 4a-g were prepared by Knoevenagel reactions of 1,3-indandione ( 1 ) with the aromatic aldehydes 2a-g followed by cyclizing Michael addition of the products thus obtained with methyl β-aminocrotonate ( 3 ). The structures of products 4 were characterized by spectal data. Positive inotropic activities were observed on electrically stimulated, left atria of giunea pigs and these effects could be attributed to calcium agonism. On the other hand, barium chloride-induced contractions of guinea pig ileum were inhibited in a dose-dependent manner.     

Cycloaddition von benzothiet an oxime,oximether und oximester

Benzothiete 1 generates by thermal ring opening an 8π electron system 2 which undergoes [8π + 2π] cycloaddition reactions with the oxime systems 3a-g . In accordance with the FMO theory the 1,3-thiazine derivatives 4a-g are formed in a regiospecific and 4f additionally in a stereospecific manner. The O-acylated adducts 4h-j enter the same cycloaddition; however, an elimination reaction 4 ← 5, 6 can provoke the addition of a second benzothiete, yielding the tetracyclic compounds 7j , and 8i,j .     

Hydrogenolysis of 1-aminopyrazoles: Synthesis of primary and secondary alkylamines

The tautomerizable N-aminopyrazolone 9 , the O-methyl 1 and N-methyl derivatives 4 were condensed with carbonyl compounds to give the alkenylaminopyrazoles 12, 2a-g and 5c , which, under mild conditions, were hydrogenated to the corresponding alkylamino derivatives. The subsequent hydrogenation of the latter ones gave different results according to the structure of the starting material. The 5-methoxy-1-alkylamino-pyrazoles 3a-g yielded the 5-methoxypyrazole 15 and the corresponding primary amines in good yields. On the contrary, N-methyl-1-alkylaminopyrazolone-5 6c gave 1-alkylpyrazolone-3 8.