4-(6-甲氧基-2-萘基)-2-(2-羟苄亚氨基)噻唑合成与表征

6-甲氧基-2-(2-溴酰基)萘与硫脲反应环合得4-(6-甲氧基-2-萘基)-2-氨基噻唑;后者与水杨醛反应制备了新化合物4-(6-甲氧基-2-萘基)-2-(2-羟苄亚氨基)噻唑,收率为72.1%～94.8%.目标物采用核磁共振、红外光谱和元素分析测试技术进行了表征;分析目标物和中间体中萘环质子偶合分裂情况.并且确定了萘环上各质子的归属.     

1-苯基-3-甲基-4-萘乙酰基-吡唑啉酮-5 (PMNAP)缩2-氨基苯并咪唑(2-AB)席夫碱及其过渡金属配合物的合成、光谱表征与质谱鉴定

在非水溶剂中合成出一种新型席夫碱试剂(H2L): 1-苯基-3-甲基-4-萘乙酰基-吡唑啉酮-5 (PMNAP)缩2-氨基苯并咪唑(2-AB)及其过渡金属铜、铅、镍和钴配合物. 由元素分析、综合滴定和质谱数据推测出配合物的组成为ML•H2O, 通过红外光谱、紫外光谱、热重谱和核磁共振氢谱对配体和配合物进行了结构表征, 同时建立了合成体系的液相色谱分离和质谱鉴定方法, 在线得到了配体共存的三种异构体和目标配合物及其相应的质谱信息. 综合各种分析结果显示: 配体在测试条件下以酮式和烯醇式结构共存, 配位时酮式可能转化为烯醇式结构, 按去质子的方式以吡唑啉酮环羟基和H2O上的两个O原子以及亚胺基上的N原子和苯并咪唑环上的含氢N原子与中心离子成键, 配合物的配位数为4.     

取代萘的质子核磁共振波谱研究

关于取代萘的核磁共振波谱,文献中主要报导α、β单取代物及少数双取代物的研究。一般萘系染料及中间体都是萘的多取代物,其中萘环质子的化学位移有时变化较为特殊。本文用WH-90 PFT-NMR仪以双共振去偶技术测定了一些萘的取代物,并探讨了α取代基的迫位效应及多取代基的空间效应对萘环质子的影响。     

2-羟基-1-萘甲醛缩氨基硫脲稀土金属配合物的合成

合成了一种新的Schiff碱配体——2-羟基-1-萘甲醛缩氨基硫脲(LH)及其6种新型稀土金属配合物ML(M=Er,Gd,Nd,Pr,Sm,Tb),其结构经UV,1H MNR和IR表征。实验结果表明,配合物同时含有M-O,M-N和M-S键形成的五元环和六元环各一个,LH为多齿配体。     

芴-氮杂萘酮-聚芳醚酮离聚物的合成与性能

以双酚芴、双酚A型二氮杂萘酮、二氟二苯酮和二氟二苯酮磺酸钠为原料, 通过调整4种单体的比例以及加料顺序控制缩聚反应, 制备了一系列具有不同离子交换容量的含芴和二氮杂萘酮联苯单元的嵌段聚芳醚酮, 简称芴-氮杂萘酮-聚芳醚酮离聚物. 采用黏度测试、傅里叶衰减全反射红外光谱(FTIR-ATR)、氢谱(1H NMR)和热失重(TGA)等分析方法, 对不同结构的芴-氮杂萘酮-聚芳醚酮离聚物的分子量、结构及热稳定性进行了表征. 实验结果表明, 采用控制缩聚法能够制备出不同离子交换容量的高分子量芴-氮杂萘酮-聚芳醚酮离聚物, 该系列离聚物具有良好的热稳定性. 对该系列离聚物膜进行了抗氧化性、水解稳定性、吸水率、耐醇性、离子交换容量和质子传导率测试. 测试结果表明, 该系列离聚物具有良好的抗氧化性、水解稳定性、耐醇性、质子传导率和适当的吸水率.     

2－羟基2＇烷氧基－1，1＇－联萘化合物的~1HMNR研究

研究了２－羟基－２＇－异丙氧基－１。１－联萘（３）等联萘化合物的~１ＨＮＭＲ谱或ＣＯＳＹ谱。此类化合物因２及２＇位取代基不同，两个萘环上同位质子不再等价，萘环质子峰增至１２组。化合物３~１ＨＮＭＲ谱峰的归属表明，萘环环电流各向异性对另一萘环质子的屏蔽作用与作者早期研究结果［１］一致。２（或２＇）位取代基上的质子的化学位移也与另一萘环平面相对位置有关。     

2—羟基2‘烷氧基—1,1’—联萘化合物的^1HMNR研究

研究了２－羟基－２＇－异丙氧基－１，１－联萘（３）等联萘化合物＾１Ｈ ＮＭＲ谱或ＣＯＳＹ谱，此类化合物因２及２＇位取代基不同，两个萘环上同位质子不再等价，萘环质子峰增至１２组。化合物３＾１ＨＮＭＲ谱峰的归属表明，萘环环电流各向异性对另一萘环质子的屏蔽作用与作者早期研究结果一致。２（或２＇）位取代基上的质子的化学位移也与另一萘环平面相对位置有关。     

超声波辅助下新型2,6-二-(苯并呋喃-2-甲酰基)吡啶衍生物的简便合成

报道了以2,6-二溴乙酰基吡啶为底物,在乙腈为溶剂、PEG-400为催化剂的条件下分别与水杨醛、取代水杨醛及2-羟基-1-萘醛利用超声波辅助的Rap-Stoermer反应合成2,6-二-(苯(萘)并呋喃-2-甲酰基)吡啶衍生物的简便方法.提供了一种将吡啶环和苯(萘)并呋喃环通过羰基联接构建成新型杂环骨架结构的新途径.该方法具有反应时间短、条件温和、收率良好的优点.产物结构经1H(13C)NMR,IR和元素分析表征.     

3-羟基哌啶氮α-碳负离子的形成及α-羟烷化反应

合成了（S）-3-羟基哌啶苯硫醚化合物6作为3-羟基哌啶氮α-碳负离子手性合成子（B）的合成等效体.化合物6经羟基去质子现场保护、萘锂（LN）还原锂化形成手性哌啶醇双负离子中间体B.双负离子B可被质子淬灭得到还原产物2a 而与羰基化合物反应则得到α-羟烷化产物12～17和少量还原产物2a.该反应具有很高的环上2,3-位非对映立体选择性 与非对称的羰基化合物反应产生新手性中心的立体选择性从50：50到77：23.     

水溶性1，8-萘酰亚胺衍生物的合成及其对有机溶剂中少量水的识别

萘二甲酸酐与2-(2-氨乙基氨基)乙醇在乙醇中反应合成了一种新型水溶性1,8-萘酰亚胺衍生物--N-[2-(2-羟乙基氨基)-乙基]-1,8-萘酰亚胺(3),其结构经1H NMR,IR,MS和元素分析表征.荧光光谱分析发现3在不同溶剂中具有不同的荧光性质,在非(或弱)极性-非质子性溶剂、极性-非质子溶剂中几乎不产生或产生较弱的荧光,而在极性-质子性溶剂中产生较强的荧光,在水中的荧光最强.这种特性使3有望用于识别有机溶剂中的少量水.     

Synthesis, structure and dynamics of methoxynaphthalene-substituted phospha-ruthenocenes and -ferrocenes

The syntheses of potassium 2-(2'-methoxynaphth-1'-yl)-3,4-dimethyl-5-phenylphospholide 4 and eta5-pentamethylcyclopentadienyl(eta5-2-(2-methoxynaphth-1-yl)-3,4-dimethyl-5-phenylphospholyl)-ruthenium(II)5 and -iron(II)6 are described. The barrier to rotation of the naphthyl group (79 kJ mol-1 and 72 kJ mol-1 in CD2Cl2 respectively) characterises 5 and 6 as potential tropos type ligands. Coordination of 5 to [PtCl2(PEt3)] gives two cis and two trans complexes [PtCl2(PEt3)5] wherein rotation about the phospholyl-naphthyl vector is slow.     

Stereoselective synthesis of optically active disilanes and selective functionalization by the cleavage of silicon-naphthyl bonds with bromine

Optically active disilanes with one chiral silicon center, (R)-1,2-dimethyl-1-(naphth-1-yl)-1,2,2-triphenyldisilane and (R)-1,2,2-trimethyl-2-(4-methoxynaphth-1-yl)-1-(naphth-1-yl)-1-phenyldisilane, were obtained by the reaction of (S)-methyl(naphth-1-yl)phenylchlorosilane (> 99% ee) with methyldiphenylsilyllithium or by the reaction of methyldiphenylchlorosilane with optically active (S)-methyl(naphth-1-yl)phenylsilyllithium and by the reaction of (S)-methyl(naphth-1-yl)phenylchlorosilane (> 99% ee) with dimethyl(4-methoxynaphth-1-yl)silyllithium. Under the optimized conditions, the reactions proceeded with almost complete inversion for the cholorosilanes and retention for the silyl anions. Optically active disilanes with two chiral centers, (1R,2R)-1,2-dimethyl-1,2-di(naphth-1-yl)-1,2-diphenyldisilane and (1S,2S)-1,2-di(4-methoxynaphth-1-yl)-1,2-dimethyl-1,2-diphenyldisilane, were obtained in high optical purity by the reactions of corresponding optically active halogenosilanes (Cl or F) with optically active silyllithiums. The silicon-silicon bond and the silicon-naphthyl bond of (R)-1,1,2-trimethyl-1,2-di(naphth-1-yl)-2-phenyldisilane and (1R,2R)-1,2-dimethyl-1,2-di(naphth-1-yl)-1,2-diphenyldisilane were cleaved without selectivity on bromination. The silicon-(4-methoxynaphth-1-yl) bond of (R)-1,2,2-trimethyl-2-(4-methoxynaphth-1-yl)-1-(naphth-1-yl)-1-phenyldisilane was regiospecifically cleaved, followed by the stereoselective cleavage of the remaining chiral silicon-naphthyl bond (94% inversion). Although the silicon-(4-methoxynaphth-1-yl) bonds of (1S,2S)-1,2-di(4-methoxynaphth-1-yl)-1,2-dimethyl-1,2-diphenyldisilane (> 99% ee) were regioselectively cleaved without silicon-silicon bond scission, remarkable racemization could not be avoided during the one-pot reaction.     

Enantiodivergence in alkylation of 1-(6-methoxynaphth-2-yl)ethyl acetate by potassium dimethyl malonate catalyzed by chiral palladium-DUPHOS complex

Alkylation of racemic 1-(6-methoxynaphth-2-yl)ethyl acetate by potassium dimethyl malonate catalyzed by a chiral palladium-DUPHOS complex afforded the substitution product with 87% ee, along with 6-methoxy-2-vinylnaphthalene that arose from an elimination process, in a 43/57 substitution/elimination ratio. The reaction performed on a mixture of quasi-enantiomeric substrates provided insight into the stereochemical course of the reaction, establishing that—for a given enantiomer of the catalyst, one enantiomer of the substrate afforded mainly the substitution product whereas the other enantiomer underwent elimination.     

Synthesis of succinimidyl-(S)-naproxen ester and its application for indirect enantioresolution of penicillamine by reversed-phase high-performance liquid chromatography

Synthesis of N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate was carried out by the reaction of (S)-naproxen with N-hydroxysuccinimide in the presence of dicyclohexyl carbodiimide. It was characterized and was used as a chiral derivatizing reagent, under mild conditions, to form diastereomers of dl-penicillamine which were resolved by reversed-phase high-performance liquid chromatography using triethyl ammonium phosphate buffer (pH 4.0, 5mM)-acetonitrile (linear gradient (30min) of acetonitrile from 30 to 70%). Excellent separation was achieved with gradient mobile phase. The detection limit was at pmol level.     

Synthesis of dinitrophenyl-l-Pro-N-hydroxysuccinimide ester and four new variants of Sanger's reagent having chiral amines and their application for enantioresolution of mexiletine using reversed-phase high-performance liquid chromatography

Four chiral derivatizing reagents (CDRs) having enantiomerically pure amines and two CDRs namely, [N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl)propionate], and [dinitrophenyl-l-Pro-N-hydroxysuccinimide ester, DNP-l-Pro-SU] were synthesized and were used to prepare diastereomers of (R,S)-mexiletine (MEX); these were separated by reversed-phase high-performance liquid chromatography (RP-HPLC). The method was validated for linearity, accuracy, limit of detection (LOD) and limit of quantification (LOQ).     

γγ-Disubstituted Itaconic Acids. Part 1. The Stobbe condensation of 1-arylnaphthyl ketones with diethyl succinate

Arylnaphthyl ketones condense with diethyl succinate yielding the stereoisomeric half-esters 2a–2d which were subjected to a series of reactions leading to 1-phenylphenanthrene and 1,1′-binaphthyl derivatives. (E)-3-Ethoxycarbonyl-4-(4-methoxynaphth-1-yl)-4-arylbut-3-enoic acids ( 2b–d ) were converted finally into the corresponding naphtho[1,2-c]fluorenones ( 9 ). The structure of the products was established by IR. and UV. spectroscopy. The effect of substituents on the relative proportions of (E)- and (Z)-half-esters 2 was determined by chromatography and UV. spectroscopy.     

Preparation,Single-crystal Structure and Antibacterial Activity of N-（（6-Bromine-2-methoxylquinoline-3-yl）benzyl）-3-morpho-line-N-（naphthalene-1-yl）propionamide

The halogenated hydrocarbon amination reaction between the original raw mate-rial N-((6-bromine-2-methoxylquinoline-3-yl)benzyl)-3-chlorine-N-(naphthalene-1-yl)propionamide and morpholine produces the target molecule N-((6-bromine-2-methoxylquinoline-3-yl)benzyl)-3-morpholine-N-(naphthalene-1-yl)propionamide (C34H32BrN3O3,Mr=610.54),and its structure was characterized by 1H NMR,IR,H RMS and X-ray single-crystal diffraction.This crystal is of triclinic system,space group P1 with a=9.315(2),b=10.3449(12),c=15.901(3),α=80.981(14),β=76.996(17),γ=74.917(13)°,V=1433.6(5)3,Z=2,Dc=1.414 g/cm3,F(000)= 632,μ(MoKα)=1.47 mm-1,the final R=0.0735 and wR=0.2457.In total,5585 independent reflections including 3727 observed ones with I 2σ(I) were collected.The dihedral angle between naphthyl and substituted quinolyl and that between phenyl and substituted quinolyl are 61.2(1) and 108.2(1)°,respectively.Through C-H…O and C-H…N hydrogen bonds among molecules,the whole molecule is stacked into a three-dimensional structure.In addition,π-π stacking among adjacent naphthalene rings makes the molecule more stable,and the morpholine ring adopts a chair conformation.The target molecule exhibits good antibacterial activity.     

Synthesis and H+, Cu2+, and Zn2+ coordination behavior of a bis(fluorophoric) bibrachial lariat aza-crown

The synthesis, protonation behavior, and Cu2+ and Zn2+ coordination chemistry of the novel bibrachial aza lariat ether (naphthalen-1-ylmethyl)[2-(20-[2-[(naphthalen-1-ylmethyl)amino]ethyl]-3,6,9,17,20,23,29,30-octaazatricyclo[23.3.1.1*11,15*]triaconta-1(29),11(30),12,14,25,27-hexaen-6-yl)ethyl]amine (L) are discussed. The macrocycle, which has two aminoethyl naphthyl moieties symmetrically appended to a 2:2 azapyridinophane structure, displays, in the pH range 2-11, six protonation steps that correspond to the protonation of the secondary amino groups. Steady-state fluorescence measurements show emissions due to the monomer and to the excimer formed between the two naphthalene fragments of the macrocycle. The time-resolved fluorescence data, obtained by the time-correlated single photon counting technique, show that a significant percentage of excimer is preformed as ground-state dimers. The ligand L forms with the metal ions Cu2+ and Zn2+ mono- and dinuclear complexes in aqueous solution. The influence of metal coordination in the fluorescence emission of L is analyzed. The acid-base, coordination capabilities, and emissive behavior of L are compared with those presented by its synthetic precursor L1, which has a tripodal tris(2-aminoethyl)amine structure functionalized at one of its terminal amino groups with a naphthyl moiety.     

Discovery of New Pyrazolopyridine,Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design,Synthesis, Docking Studies,and Anti-Proliferative Activity

New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-⁻C² functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C²-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC₅₀ values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC₅₀ 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC₅₀ ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC₅₀ 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.     

(2S)-(+)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮的不对称合成

以(2R,3R)-酒石酸二甲酯为手性辅助剂,6-甲氧基-2-丙酰基萘经缩酮化、溴化铜不对称溴化、水解等反应合成了(2S)-2-溴-1-(6'-甲氧基-2'-萘基)丙-1-酮。总收率94%。