新型碳苷糖类维生素D_2衍生物的合成

以D-葡萄糖为原料,经碳苷化反应,酰化反应和脯氨酸-DIPEA催化的aldol反应制得2个碳苷糖[1-(4'-羟基苯基)-4-C-β-四乙酰基葡萄糖基-3-烯-2-酮(5a)和1-(3-羟基苯基)-4-C-β-四乙酰基葡萄糖基-3-烯-2-酮(5b)];5与琥珀酸维生素D2经Steglich酯化反应合成了2个新型碳苷糖类维生素D2衍生物,其结构经1H NMR,13C NMR和HR-ESI-MS表征。     

4-[4’-(二乙基氨基)苯乙烯基]-N-(4″-乙氧基苯基)-N-(4-氨基苯基)苯胺的合成

对硝基苯胺和对碘苯乙醚经取代反应制得4’-硝基-(4-乙氧基苯)苯胺(3);3与对氟苯甲醛经取代反应制得含乙氧基的脂溶性中间体4-[(4’-乙氧基苯基)(4″-硝基苯基)氨基]苯甲醛(5);5与4-N,N-二乙基胺基苄基三苯基鏻盐经Witting成烯反应后经Pd/C催化、水合肼还原合成了新化合物4-[4’-(二乙基氨基)苯乙烯基]-N-(4″-乙氧基苯基)-N-(4-氨基苯基)苯胺,其结构经1H NMR,IR,MS和元素分析表征。     

温和条件下[2-氨基-3-(苯并噻唑-2-基)-4H-色烯-4-基]膦酸酯衍生物的简便合成

含有不同取代基的(E)-2-(苯并噻唑-2-基)-3-(2-羟基苯基)丙烯腈与亚磷酸二苯酯在水中,无催化剂催化即可发生Michael加环/环化串联反应,可以高产率地生成相应的[2-氨基-3-(苯并噻唑-2-基)-4H-色烯-4-基]膦酸酯衍生物.同时,也尝试了水杨醛、2-(苯并噻唑-2-基)乙腈和亚磷酸二苯酯在Et_3N催化下的三组分一锅法反应合成相应的膦酸酯衍生物.     

1-[二-(4-氟苯)甲基]-4-酰基取代哌嗪类衍生物的合成及波谱分析

1-[二-(4-氟苯)甲基]-4-取代哌嗪是一类重要的药物中间体,随着哌嗪环4-位引入不同的取代基可以产生不同的生物活性,如治疗偏头痛药物氟桂利嗪、洛美利嗪,抗氧化剂[1,2]、钙拮抗剂[3]、癌症治疗中多种抗药性的调节剂(modulator of MDR)[4,5]等;此外,含有酰基结构单元的哌嗪衍生物具有降压活性,如哌唑嗪等[6,7].因此根据药学上的拼合原理,我们以哌嗪为母体,采用哌嗪环先引入二-(4-氟苯)甲基后引入酰基的策略,设计合成了九个未见文献报道的1-[二-(4-氟苯)甲基]-4-酰基取代哌嗪类衍生物(4a～4i),如下图所示,其结构用红外、质谱、核磁、元素分析进行了分析表征,并总结了其波谱特征.此类化合物对治疗偏头痛和高血压的活性研究正在进行之中.     

β-(3,4-二羟基苯基)-α-羟基一N-[(R)-3-苯基-1-乙氧酰基丙基]丙酰胺的合成

以3,4-二羟基苯甲醛为原料,经开环、Knoevenagel缩合、水解和Clemmemen还原反应合成了丹参素(5);5与(R)-2-胺基-4-苯基丁酸乙酯在DCC/DMAP作用下,脱去一分子水合成了β-(3,4-二羟基苯基)-α-羟基-N-[(R)-3-苯基-1-乙氧酰基丙基]丙酰胺(8).8的结构经1H NMR,IR和MS表征.     

新型异噁唑啉类化合物的合成及其抗肿瘤活性

以3,4-二氟苯甲醛为起始物,经4步反应合成了关键中间体N-[{3-[3-氟-4-(1-哌嗪基)苯基]4,5-二氢-5-异噁唑}甲基]乙酰胺(4);4与取代苯磺酰氯经亲核取代反应合成了6个新型的异噁唑啉类化合物(6a～6f),其结构经1H NMR和MS表征.采用MTT法对6a～6f进行初步生物活性测试结果表明,部分化合...     

胆酸甲酯(甲基)丙烯酰基衍生物的合成

以(甲基)丙烯酰氯为酰化剂,三乙胺做缚酸剂合成了分子中含有1~3个(甲基)丙烯酰基的胆酸衍生物。结果显示,以酰氯作酰化试剂,胆酸甲酯分子中3个羟基的反应活性顺序是:C3-OH>C12-OH>C7-OH。     

基于4,6-二甲基-2-巯基嘧啶结构的联烯衍生物的合成及抗菌活性研究

以4,6-二甲基-2-巯基嘧啶、3-溴丙炔和取代苯甲醛为原料,经过亲核取代和加成反应,以42～78%的分离收率得到了11个4-((4,6-二甲基嘧啶-2-基)硫代)-1-(取代苯基)-2-丁炔基乙酸酯衍生物3(a-k)。在金属镍的催化下,4-((4,6-二甲基嘧啶-2-基)硫代)-1-(取代苯基)-2-丁炔基乙酸酯衍生物(3)与三甲基铝发生S_N2’取代反应合成了11个含有4,6-二甲基-2-巯基嘧啶结构的联烯衍生物4(a-k)。探讨了各种反应条件对目标产物收率的影响,并且对这些条件进行了优化。结果表明,在60℃,四氢呋喃作溶剂,碳酸钾作碱,用2mol%NiCl_2/4mol%PPh_3催化三甲基铝试剂与4-((4,6-二甲基嘧啶-2-基)硫代)-1-(取代苯基)-2-丁炔基乙酸酯衍生物(3)进行S_N2’取代反应,可以顺利地以22～63%的分离收率得到含有4,6-二甲基-2-硫基嘧啶结构的联烯衍生物。所有目标化合物均经~1H(~(13)C)NMR,IR,HRMS分析对其结构进行确证。该类化合物的合成方法具有操作简单和反应条件温和的优点。经体外活性测试表明有5个化合物对大肠杆菌有一定的抑制作用,其最小抑制浓度可达4 ug·mL~(-1)。     

β-（3，4-二羟基苯基）-α-羟基-N-[（R）-3-苯基-1-乙氧酰基丙基]丙酰胺的合成

以3,4-二羟基苯甲醛为原料,经开环、Knoevenagel缩合、水解和Clemmensen还原反应合成了丹参素（5）;5与（R）-2-胺基-4-苯基丁酸乙酯在DCC／DMAP作用下,脱去一分子水合成了β-（3,4-二羟基苯基）-α-羟基-N-[（R）-3-苯基-1-乙氧酰基丙基]丙酰胺（8）。8的结构经^1H NMR,IR和MS表征。     

新型1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物的合成

以二乙醇胺为原料,经溴化、环合、N-烷基化和还原4步反应制得关键中间体——4-[4-(4-甲氧基苯基)哌嗪-1-基]苯胺(4);4与酰氯经酰基化反应合成了11个新型的1-(4-氨基苯基)-4-(4-甲氧基苯基)哌嗪衍生物,其结构经1H NMR,FT-IR,ESI-MS和元素分析表征。     

Synthesis of aromatic polyethers by Scholl reaction. V. Synthesis and polymerization of 1,3-bis[4-(1-naphthoxy) benzoyl]benzene, 1,4-bis[4-(1-naphthoxy)benzoyl]benzene,bis[4-(1-naphthoxy)phenyl]methane, 1,3-bis[4-(1-naphthoxy) phenylmethyl]benzene,and 1,4-bis-[4-(1-naphthoxy)phenylmethyl]benzene

This article describes the synthesis and the cation-radical polymerization (Scholl reaction) of 1,3-bis[4-(1-naphthoxy) benzoyl] benzene ( 6 ) and 1,4-bis[4-(1-naphthoxy) benzoyl]- benzene ( 7 ) initiated by FeCI₃. This polymerization produced poly(ether ether ketone ketone)s (PEEKK) of number average molecular weight (M?_n) up to 5400 g/mol. The synthesis of bis[4-(1-naphthoxy) phenyl] methane ( 8 ), 1,3-bis[4-(1-napthoxy) phenylmethyl] benzene ( 9 ), and 1,4-bis[4-(1-naphthoxy) phenylmethyl] benzene ( 10 ) are also described. Polyethers of M?_n up to 15400 g/mol at a FeCl₃/monomer molar ratio of 2/1 were obtained. An increased polymerizability of the monomers 9 and 10 containing two CH₂ groups versus that of the corresponding monomers containing two carbonyl groups ( 6 and 7 ) was observed. This enhanced polymerizability was explained based on the increased nucleophilicity of monomers 9 and 10 .     

一类新型共轭芳炔二胺的合成及其光电性质

以对乙炔基苯胺为首末端砌块,经Sonogashira或Eglinton偶合反应,设计并合成了4种新型的氨基封端的结构对称的共轭芳炔化合物(1～4),其结构经~1H NMR,~(13)C NMR,IR和MS表征.紫外和荧光光谱实验表明1～4均具有良好的光化学性质,其中1,4-双(4-氨基苯乙炔基)苯(2)和1,2-双[4-(4-氨基苯乙炔基)苯基]乙炔(4)在c为10~(-7)mol·L~(-1)时仍具有良好的荧光性.电化学结果表明,电位在0 V～1 V时,2在0.8 V附近有一对不可逆的氧化还原峰,经过多圈循环伏安扫描后在电极表面得到一层有色的聚合膜.     

Synthesis and Reactions of Halo-,Arylazo-substituted 3-(3-(1-naphthyl)acryloyl)tropolones.Formation of(Naphthalen-1-yl)vinyl)substituted Heterocycle-fused Troponoid Compounds

The starting substrate 3‐(3‐(1‐naphthyl)acryloyl)tropolone ( 3 ) was achieved by the aldol condensation reaction of 3‐acetyltropolone with 1‐naphthaldehyde. Compound 3 reacted with bromine to afford 7‐bromo‐3‐ (3‐(1‐naphthyl)acryloyl)tropolone ( 4 ), 5,7‐dibromo‐3‐(3‐(1‐naphthyl)acryloyl)tropolone (5) according to the molar ratio of the reactants. Iodination of 3 gave 7‐iodo‐3‐(3‐(1‐naphthyl)acryloyl)tropolone ( 6 ). Azo‐coupling reactions of 3 gave the 5‐arylazo‐3‐(3‐(1‐naphthyl)acryloyl)tropolones ( 7 – 8 ). Compounds 3 , 4 , 6 reacted respectively with hydroxyamine to give the corresponding 3‐[2‐(1‐naphthyl)vinyl]‐8H‐cyclohepta[d]isoxazol‐8‐ones ( 9 – 11 ). The reactions of 3 , 5 with phenylhydrazine and substituted phenylhydrazines gave 3‐[2‐(1‐naphthyl)vinyl]‐1‐phenylcyclohepta[c]pyrazol‐8(1H)‐ones ( 12 – 18 ).     

Reactivities of novel [hydroxy(tosyloxy)iodo]arenes and [hydroxy(phosphoryloxy)iodo]arenes for alpha-tosyloxylation and alpha-phosphoryloxylation of ketones

Novel [hydroxy(tosyloxy)iodo]arenes bearing 2-thienyl, 3-thienyl, N-tosyl-4-pyrazolyl, 3-trifluoromethylphenyl, and 3,5-bis(trifluoromethy)phenyl as an aromatic group, and [hydroxy(phosphoryloxy)iodo]arenes bearing N-tosyl-4-pyrazolyl, 3-trifluoromethylphenyl, and 3,5-bis(trifluoromethy)phenyl as an aromatic group, were prepared. alpha-Tosyloxylation and alpha-phosphoryloxylation of ketones with these compounds were carried out, respectively. Their reactivities were compared with that of the parent [hydroxy(tosyloxy)iodo]benzene and [hydroxy(phosphoryloxy)iodo]benzene, respectively, and consequently [hydroxy(tosyloxy)iodo]arenes and [hydroxy(phosphoryloxy)iodo]arenes bearing 3-trifluoromethylphenyl and 3,5-bis(trifluoromethy)phenyl as an aromatic group showed the best reactivity. These new compounds can be used as powerful alpha-tosyloxylation and alpha-phosphoryloxylation reagents, instead of the parent [hydroxy(tosyloxy)iodo]benzene and [hydroxy(phosphoryloxy)iodo]benzene.     

S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲的合成及其iNOS抑制活性

以2-巯基苯并咪唑(1)为原料,经缩合和还原得到2-(4-氨基苯硫基)苯并咪唑(3),再与异硫氰酸苯甲酰酯或异硫氰酸烃基酯反应得到取代硫脲(5和7),最后与卤代烃反应得到20个新的S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲化合物(6和8),其结构经IR,¹HNMR,MS及元素分析确证.初步的药理试验表明,20个目标化合物均有不同程度的iNOS抑制活性,其中化合物6b,8d和8f的iNOS抑制活性与阳性对照药氨基胍相当.     

无溶剂NH2SO3H催化下超声促进环酮与芳香醛的Aldol缩合

以NH₂SO₃H作催化剂, 在无溶剂条件下用超声技术合成了一系列α,α'-双亚苄基环酮衍生物, 反应在15～45 min内完成, 产率76%～92%, 后处理简便, 且对环境友好.     

A Novel Procedure to Synthesize 3‐Chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl Azetidin‐2‐ones and Exploration of Their Anti‐Inflammatory Activity

Some new derivatives of 3‐chloro‐1‐(4a,10b‐diazaphenanthrene‐2‐yl)‐4‐phenyl azetidin‐2‐one were synthesized through the reaction of N‐{4‐[phenyldiazenyl] phenyl}‐N‐[phenyl methylene] amine with 4‐[phenyldiazenyl] aniline. The resulting 3‐chloro‐4‐phenyl‐1‐{4‐[phenyldiazenyl] phenyl} azetidin‐2‐one intermediate in benzene was irradiated in a Pyrex vessel with 350 nm UV light in a photochemical reactor to give the desired derivatives (4a–j) . Structures of the new compounds were verified on the basis of spectral and elemental methods of analyses. Nine of the prepared compounds were tested for their anti‐inflammatory effects; most of these compounds showed potent and significant results compared with indomethacin.     

2,4和8-支噁二唑衍生物的三光子吸收和三光子上转换荧光

用飞秒Ti:sapphire激光测定了3个对称噁二唑衍生物4-{N,N-双[4-(4-[5-(4-叔丁基苯基)-1,3,4-噁二唑-2]苯乙烯基)苯基]氨基}苯甲醛(Bis-oxa)、2,5-双{4-[2-N,N-双(4-{4-[5-(4-叔丁基苯基)-1,3,4-噁二唑-2]苯乙烯基}苯基)氨基苯乙烯基]苯基}-1,3,4-噁二唑(Quadri-oxa)和2,5-双(4-{2-N,N-双[({3,5-二[5-(4-叔丁基苯基)-1,3,4-噁二唑-2]苯基}乙烯基)苯基]氨基苯乙烯基}苯基)-1,3,4-噁二唑(Octu-oxa)的三光子吸收谱和三光子荧光光谱. 在1260 nm飞秒激光激发下, 2,4和8-支噁二唑衍生物的三光子吸收系数分别为5.0×10^-5, 10.0×10^-5和10.0×10^-5 cm³/GW², 三光子频率上转换荧光发射波长分别为533, 544和551 nm. 研究了多支化合物线性吸收和透过、单光子荧光及量子产率、荧光寿命、多光子荧光光谱和三光子吸收系数谱. 对称多支噁二唑衍生物具有很强的三光子吸收和上转换荧光性质.     

合成SGLT2抑制剂埃格列净的新方法

以D-(+)-葡萄糖酸内酯为原料,经三甲硅基保护羟基后与5-溴-2-氯-4′-乙氧基二苯甲烷偶联制得(2S,3R,4S,5S,6R)-2-［4-氯-3-(4-乙氧苄基)苯基］-6-(羟甲基)-2-甲氧基四氢-2H-吡喃-3,4,5-三醇（2）; 2经羟基保护、氧化和羟醛缩合等5步反应制得(3S,4S,5R,6S)-3,4,5-三(苄氧基)-6-［4-氯-3-(4-乙氧苄基)苯基］-2-(羟甲基)-6-甲氧基四氢-2H-吡喃-2-甲醛（7）; 7经还原、脱苄同时关环制得埃格列净(1S,2S,3S,4R,5S)-5-［4-氯-3-(4-乙氧苄基)苯基］-1-(羟甲基)-6,8-二氧杂二环［3.2.1］辛烷-2,3,4-三醇,其结构经¹H NMR和LC-MS表征。     

New viologen analogs: 1,4-bis[2-(pyridin-4-yl)ethenyl]benzene quaternary salts

Alkylation of 1,4-bis[2-(pyridin-4-yl)ethenyl]benzene with alkyl p-toluenesulfonates and dimethyl sulfate gave new viologen analogs, 1-alkyl-4-(2-{4-[2-(1-alkylpyridinium-4-yl)ethenyl]phenyl}ethenyl)-pyridinium bis(p-toluenesulfonates) and sulfate. Their derivatives with tetrafluoroborate and tetraphenylborate ions were also obtained. Spectral properties of the synthesized compounds were examined, and their structure was determined by X-ray analysis.