HPLC法测定人体尿液中的4'-羟基和6-甲氧基黄烷酮

黄烷酮(Flavanone)属于黄酮类化合物(Flavonoids),具有2-苯基色原酮化学结构.黄烷酮类化合物广泛存在自然界,其衍生物大多从天然植物中提取而得,取代基多为羟基、甲氧基、苄氧基、异戊烯基、香叶基等,是多种药用植物有效成分之一.据有关文献报道,许多黄烷酮类化合物具有抗菌、消炎、抗肿瘤、抗HIV病毒、抗诱变、抗氧化、抗癌活性等诸多生物活性~([1]).由于其显著的生物、药理活性及独特的可靼性结构,引起了化学和医药工作者浓厚的研究兴趣.     

3-取代-B-降胆甾醇-6-(N-甲基)缩氨硫腙衍生物的合成及抗肿瘤活性评估

从胆甾醇出发,经过4步反应,合成了系列不同的3-取代-B-降胆甾醇-6-(4′-甲基)缩氨硫腙衍生物,采用IR、NMR及HRMS对合成物进行了结构表征。同时,分别采用人乳腺癌细胞(MCF-7)、人卵巢癌细胞(SKOV3)、人乳腺导管癌细胞(T47D)及人正常肾上皮细胞(HEK293T),研究了目标产物对这些细胞的抑制生长增殖活性。结果表明,除了乙酯基取代化合物外,当底物中3-羟基改变成为其它酯取代基或含氮的肟基及肟醚官能团后,原底物的细胞毒性显著降低。然而,3-乙酯基的存在对底物的抑制肿瘤细胞生长增殖活性没有明显影响,却大大降低化合物对人正常肾上皮细胞(HEK293T)的抑制生长增殖活性。     

6-位修饰的吉非替尼衍生物合成及细胞毒活性研究

以2-氨基-4,5-二甲氧基苯甲酸为起始原料,经关环,选择性脱甲基,醋酸酐保护,氯代,与3-氯-4-氟苯胺取代,去保护得到关键中间体4-(3-氯-4-氟苯胺)-7-甲氧基-喹唑啉-6-醇.再经过6-位羟基成醚、成酯反应合成了共计23个吉非替尼衍生物.所有目标化合物通过IR,1H NMR,13C NMR,HRMS等结构确证.并采用四甲基偶氮唑盐(MTT)法对所得目标化合物进行了细胞毒活性测试,结果发现部分化合物具有一定的抑制活性,其中化合物7b,7c,7d,8a,8m抑制人非小细胞肺癌细胞(A549)增殖活性和化合物7c,8m抑制人肝癌细胞(Hep G-2)增殖活性与吉非替尼相当.     

(±)-Diplacone与(±)-3'-O-methyldiplacone的全合成

以廉价的香草醛,3,4-二羟基苯甲醛和2,4,6-三羟基苯乙酮为初始原料,经过C-香叶基化、羟基保护、羟醛缩合、脱去保护基以及催化环化等步骤,以11%和20%的总收率实现了两个天然香叶基黄烷酮(±)-diplacone与(±)-3′-O-methyldiplaone的首次全合成,其结构经¹H NMR, IR和MS表征。     

新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性

根据活性亚结构拼接原理,通过紫罗兰酮与(取代)苯甲醛反应合成了紫罗兰酮基双查尔酮,然后经与氨基硫脲缩合得到一系列未见报道的新型含紫罗兰酮、查尔酮及氨基硫脲3种优势结构单元的杂化体,它们的化学结构经傅里叶变换红外光谱(FT-IR)、核磁共振波谱(~1H NMR、~(13)C NMR)、元素分析及质谱(MS)等测试技术所证实。采用溴化噻唑蓝四氮唑(MTT)法初步测定其体外抗肿瘤活性(乳腺癌细胞(MCF-7),肝癌细胞(Hep G2),肺癌细胞(A549)),结果表明,对于不同类型的肿瘤细胞,化合物展现较好的增殖抑制活性。尤其是化合物3a与3b对MCF-7细胞展现较强的抗增殖活性,半数致死量(IC_(50))值分别为10.83和7.62μmol/L,化合物3e对A549细胞显示一定的增殖抑制活性效果(IC_(50)值为13.36μmol/L),化合物3f对Hep G2细胞表现了高效的抗增殖活性(IC_(50)值为8.55μmol/L)。目标物的抗增殖活性与紫罗兰酮结构及查尔酮环上不同电子效应的取代基有关。     

2-苯甲酰基嘧啶类化合物的合成与生物活性

2-嘧啶氧基-N-芳基苄胺类化合物结构经过两次骨架结构优化后得到2-苯甲酰基嘧啶类化合物二次先导结构.在二次先导结构基础上,共设计并合成了36个化合物,所有化合物结构经1H NMR、13C NMR、HRMS确认,并进行了室内杀菌活性筛选,对各部位取代基进行了逐次优化.结果表明2-苯甲酰基嘧啶类化合物中R1取代基以2位卤素或烷基取代的苯环或杂环活性最好;中间苯环6位引入氟原子活性保持;嘧啶环4,6位甲氧基取代活性较好,5位甲基取代活性大大降低;羰基被还原为羟基后活性消失.其中2,3-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHl)、2,5-二氯-N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)苯氧基]-N-甲基苯甲酰胺(4AHn)及N-[2-(4,6-二甲氧基嘧啶-2-甲酰基)-3-氟苯氧基]-N,2-二甲基苯甲酰胺(4AFd)对黄瓜白粉病的杀菌活性与对照样苯菌酮相当.     

N9位芳基取代嘌呤-8-酮类衍生物的合成及抗肿瘤活性

合成了一系列N9位芳基取代嘌呤-8-酮类衍生物, 利用核磁共振氢谱(¹H NMR)、 核磁共振碳谱(¹³C NMR)和高分辨质谱(HRMS)进行了结构确证. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物的体外抗肿瘤细胞增殖活性. 结果表明, 嘌呤酮环的C2位及N9位的取代对活性有较大影响, C2位引入对位由含氮六元环取代的苯胺, N9位引入对三氟甲基苯均有利于提高抗肿瘤活性. 化合物12c对人白血病细胞(K562)、 人前列腺癌细胞(PC-3)、 人乳腺癌细胞(MDA-MB-231)及人结肠癌细胞(HCT116)的抑制效果明显优于阳性对照药R-Roscovitine.     

甾体肟醚化合物的合成及抗肿瘤活性研究

肟醚类化合物往往表现出很好的杀虫、除草、抗菌、抗病毒以及抗肿瘤等生理活性,因而受到人们的广泛关注.从胆甾醇、豆甾醇出发,通过不同的合成路线,制备得到系列3-取代、6-取代及22-取代甲氧基肟醚和苄氧基肟醚甾体化合物,通过IR、NMR及MS等现代分析方法对合成物进行了结构表征.同时,分别采用人胃癌细胞(SGC-7901)、人肝癌细胞(Bel-7404)和鼻咽癌细胞(CNE-2)对合成产物及部分合成中间体进行了体外抑制肿瘤细胞生长增殖活性研究.结果表明,某些具有22-取代结构的甲氧肟醚及苄氧肟醚甾体化合物对这些肿瘤细胞株表现出较好的抑制活性,其中22-降-3β-羟基-22-苄氧肟基-豆甾-6-缩胺硫腙(15)对人鼻咽癌细胞CNE-2的IC50值为5.7μmol/L.     

肟醚噻二唑硫醚化合物的合成及其抗肿瘤活性

将2-巯基-5-取代基-1,3,4-噻二唑经与β-氯苯丙酮取代、盐酸羟胺肟化和氯甲基噁二唑醚化,合成了6种3-(5-取代基-1,3,4-噻二唑-2-硫代基)-1-苯基丙酮-O-(5-苯基-1,3,4-噁二唑-2-甲基)肟醚化合物(4a~4f),用1H NMR、IR、MS和元素分析表征了其结构。 用MTT法测试了6种目标化合物对人黑色素瘤细胞株B16、人白血病细胞株HL60和人肝癌细胞株SMMC-7721的体外细胞毒活性。 测试结果表明,部分化合物对3种癌细胞具有潜在的体外生长抑制活性。     

新型色酮衍生物的合成及其抗胃癌细胞(SGC-7901)活性

取代苯甲醛与取代2-羟基苯乙酮缩合形成α,β-不饱和酮(4a~4 f);4用H2O2氧化关环制得取代-3-羟基-2-取代苯基色酮(5a~5 f);5与2-氯-5-氯甲基吡啶反应合成了6个新型的含二氯五氯甲基吡啶结构的色酮类衍生物(6a~6 f),其结构经1H NMR,13C NMR和元素分析表征。初步体外活性实验结果表明,部分化合物具有较好的抗胃癌细胞(SGC-7901)活性。     

New Synthetic Routes to Biologically Interesting Geranylated Flavanones and Geranylated Chalcones: First Total Synthesis of (±)‐Prostratol F,Xanthoangelol, and (±)‐Lespeol

A new and efficient synthetic approach to biologically interesting geranylated flavanones and geranylated chalcones is described. Thus, the first total syntheses of the geranylated flavanones (±)‐prostratol F ( 1 ), (±)‐8‐geranyl‐3′,4′,7‐trihydroxyflavanone ( 2 ), and (±)‐6‐geranyl‐5,7‐dihydroxy‐3′,4′‐dimethoxyflavanone ( 3 ) were carried out starting from 2,4‐dihydroxyacetophenone ( 10 ) and 2,4,6‐trihydroxyacethophenone ( 17 ) in five to six steps (Schemes 2 and 3). The geranylated chalcones xanthoangelol ( 4 ), 3‐geranyl‐2,3′,4,4′‐tetrahydroxychalcone ( 5 ), (±)‐lespeol ( 6 ), and lespeol derivatives (±)‐ 7 – 9 were synthesized starting from 2,4‐dihydroxyacetophenone ( 10 ) in three to four steps (Schemes 2 and 6).     

Penning electron spectra from ionization of hydrogen atoms by He(2S) and He(2S) metastables

Separate Penning electron spectra were measured resulting from the ionization of H atoms by He(2¹S) and He(2³S) metastables in thermal collisions. From these results potential parameters of the diatomics He(2¹S)-H(²S) (²Σ) and He(2³S)-H(²S) (²Σ) as well as the cross-section ratio σ(singlet)/σ(triplet) are derived.     

A novel entry into a new class of spiroheterocyclic framework: regioselective synthesis of dispiro[oxindole-cyclohexanone]pyrrolidines and dispiro[oxindole-hexahydroindazole]pyrrolidines

2,6-Bis(arylmethylidene)cyclohexanones undergo a regioselective 1,3-dipolar cycloaddition reaction with the azomethine ylide derived from isatin and sarcosine by a decarboxylative route affording a series of 1-N-methyl-spiro[2.3¹]oxindole-spiro[3.2¹¹]6¹¹-arylmethylidenecyclohexanone-4-aryl-pyrrolidines which were further annulated to give a series of novel 1-N-methyl-spiro[2.3¹]oxindole-spiro[3.7¹¹](3¹¹-aryl)Δ^111,711a-hexahydro-2H-indazole-4-aryl-pyrrolidines. The structures of which were established by spectroscopic techniques as well as single crystal X-ray analysis.     

Microstructure determination of N-vinyl-2-pyrrolidone/butyl acrylate copolymers by NMR spectroscopy

The copolymer composition of N-vinyl-2-pyrrolidone/butyl acrylate (V/B) copolymers was determined from the quantitative ¹³C{¹H} NMR spectra. The monomer reactivity ratios for N-vinyl-2-pyrrolidone (V) and butyl acrylate (B) were found to be r_V=0.11±0.07, r_B=0.54±0.19, using the Kelen–Tudos and non-linear least-square error-in-variable (EVM) methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers are overlapping and complex. The complete spectral assignment of the carbon and proton NMR spectra were done by employing distortionless enhancement by polarization transfer (DEPT) and two-dimensional (2D) ¹³C–¹H heteronuclear single quantum correlation spectroscopy experiments. The 2D total correlation spectroscopy (TOCSY) (¹H–¹H homonuclear TOCSY) NMR spectrum was used to ascertain the various geminal and vicinal couplings in the copolymer.     

Synthesis of new N-substituted imidazolyl and 1H-1,2,4-triazolyl derivatives of (η-arene)(η-cyclopentadienyl)iron(II) salts

A series of new imidazolyl and 1H-1,2,4-triazolyl derivatives of (η⁶-arene)(η⁵cyclopentadienyl)iron(II) salts have been prepared by reaction of the corresponding chloroarene complexes with the sodium salts of the heterocycles. Good yields of N-substituted products were obtained in all cases under very mild conditions. In contrast to substitution by primary and secondary amines, both chlorines were displaced from [(η⁵-1,2-dichlorobenzene)(η⁵-Cp)Fe][PF₆], indicating electron withdrawal by the imidazolyl and triazolyl groups. Detailed ¹H and ¹³C NMR analysis confirmed this point. NOE difference spectra were used for ¹³C assignments, and evidence for conformational isomers in the 1,2-disubstituted complexes is presented.     

基于稳定同位素的5种蔬菜产地真实性判别

为保护蔬菜产地真实性,以上海市场5种常见蔬菜(生菜、茼蒿、辣椒、番茄和黄瓜)为研究对象,应用单因素方差分析上海和其他产地蔬菜的 δ13 C、δ15 N、δ2 H和 δ18 O值差异,并通过主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)建立上海地产蔬菜真实性判别模型.结果表明,上海地产5种蔬菜总的δ15 N、δ...     

Synthesis and characterization of two cyclic organosiloxanes by multinuclear NMR spectroscopy and X-ray crystallography

1,3-[2′,6′-Pyridinebis(methyleneoxy)]-1,3-bis(diphenyl)cyclodisiloxane (9) and 2,6-pyridinebis(1,1-diphenylethoxy)diphenylsilane (11) were obtained from 2,6-pyridinediol derivatives with dichlorodiphenylsilane. An N→Si interaction is present in 2,6-pyridinebis(1,1-diphenylethoxy)diphenylsilane, which also shows fluxional behavior. The activation energy of 13.2 kcal mol⁻¹ for 11 was obtained for the intramolecular exchange between the phenyl groups from a variable-temperature ¹H-NMR study. The compounds were characterized by ¹H-, ¹³C- and ²⁹Si-NMR and their structures were established by X-ray crystallographic studies.     

1,3,2-Diazastanna-[3]ferrocenophanes bearing alkyn-1-yl groups at tin and their 1,1-organoboration with triethylborane—molecular structure of a novel spirotin compound

2,2-Dichloro-1,3-bis(trimethylsilyl)-1,3,2-diazastanna-[3]ferrocenophane (3) reacts with lithium alkynides LiCCR¹ to give the corresponding di(alkyn-1-yl)tin derivatives 4a (R¹=^tBu) and 4b (R¹=SiMe₃). 1,1-Organoboration of 4 with triethylborane affords the spirotin compounds 5 which contain both a ferrocenophane and a stannacyclopentadiene ring. The crystal structure of 5b was determined by X-ray analysis. The compounds 4 and 5 were characterised in solution by multinuclear magnetic resonance (¹H-, ¹¹B-, ¹³C-, ¹⁵N-, ²⁹Si-, ¹¹⁹Sn-NMR), using pulsed field gradients in HMBC experiments for the ¹H detected ¹⁵N- and ¹¹⁹Sn-NMR signals. The compound 5b was also studied by solid-state ¹³C, ²⁹Si and ¹¹⁹Sn MAS NMR in order to correlate liquid and solid-state NMR data with the structural evidence.     

Theoretical determination of the ionization potentials of the 1σ and 2σ electrons of CO(Σ)

Large-basis-set calculations of near Hartree-Fock accuracy were performed on CO⁺(1σ-hole ²Σ⁺) and CO⁺)2σ-hole, ²Σ⁺); correlation energies for these systems and for CO were calculated using an atoms-in-molecule approach, relativistic energies and vibrational structure corrections were also considered. The results are: IP(CO, 1σ) = 542.4 (542.57) eV, IP(CO,2σ) = 297.0 (296.24) cV, D_c(CO, ¹Σ⁺) = 10.8 (11.1) Ev, D₃(CO⁺, 1σ, ²Σ⁺) = 11.9 eV, D_e(CO⁺, 2σ, ²Σ⁺) = 9.1 eV, where IP and D_e stand respectively for ionization potential and dissociation energy, and where the numbers in parentheses refer to the most recent experimental values. The electron transfers resulting from the ionization of inner-shell electrons are discussed. Finally a quantitative correlation is developed correlating absolute chemical shifts to charge densities. Agreement between the calculated values and those derived from the correlation is quite satisfactory.     

A Gaussian-2 ab initio study of [C2H5S] ions: III. H2 and CH4 eliminations from CH3CHSH and CH3SCH2

Gaussian-2 ab initio calculations were performed to examine the six modes of unimolecular dissociation of cis-CH₃CHSH⁺ (1⁺), trans-CH₃CHSH⁺ (2⁺), and CH₃SCH₂⁺ (3⁺): 1⁺→CH₃⁺+trans-HCSH (1); 1⁺→CH₃+trans-HCSH⁺ (2); 1⁺→CH₄+HCS⁺ (3); 1⁺→H₂+c-CH₂CHS⁺ (4); 2⁺→H₂+CH₃CS⁺ (5); and 3⁺→H₂+c-CH₂CHS⁺ (6). Reactions (1) and (2) have endothermicities of 584 and 496 kJ mol⁻¹, respectively. Loss of CH₄ from 1⁺ (reaction (3)) proceeds through proton transfer from the S atom to the methyl group, followed by cleavage of the C–C bond. The reaction pathway has an energy barrier of 292 kJ mol⁻¹ and a transition state with a wide spectrum of nonclassical structures. Reaction (4) has a critical energy of 296 kJ mol⁻¹ and it also proceeds through the same proton transfer step as reaction (3), followed by elimination of H_2. Formation of CH₃CS⁺ from 2⁺ (reaction (5)) by loss of H₂ proceeds through protonation of the methine (CH) group, followed by dissociation of the H₂ moiety. Its energy barrier is 276 kJ mol⁻¹. On both the MP2/6-31G* and QCISD/6-31G* potential-energy surfaces, the H₂ 1,1-elimination from 3⁺ (reaction (6)) proceeds via a nonclassical intermediate resembling c-CH₃SCH₂⁺ and has a critical energy of 269 kJ mol⁻¹.