一类新型的双β-氨基醇的合成及催化硼烷对芳酮的不对称还原反应

以L-半胱氨酸盐酸盐出发，经与二卤代烷偶联，成酯和格氏反应制得三种双手性β-氨基醇，1,2-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]乙烷(4a)，1,3-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]丙烷(4b)，1,4-双[R-2-氨基-3-羟基-3,3-二苯基丙硫基]丁烷(4c)。将此类双手性β-氨基醇与硼烷在THF溶液中反应，in situ制备双手性恶唑硼烷催化硼烷对芳酮的不对称还原，产物苯乙醇的光学收率达72.8%、α-溴代苯乙醇的光学收率达91.4%。     

2-[4-取代苯基-2-氧-3-酰氨基-1-吖丁啶基]-2-苯基乙酸类化合物的合成

用叠氮钠和D-苯基甘氨酸为原料合成了2-[4-取代苯基-2-氧-3-酰氨基-1-吖啶基]-2-苯基乙酸类化合物. 在叠氮乙酰氯和亚胺化合物在三乙胺存在下在-78℃时进行环缩合反应, 可导致立体专一性合成顺-甲基-2-(4-取代苯基-2-酮-3-叠氮-1-吖啶基)-2-苯基乙酸, 催化氢化或硫化氢可减少叠氮基和得到氨基β-内酰胺后者被酰化生成α-酰氨基-β-内酰胺, 在温和碱性条件下选择性地氢化酯基既不会影响β-内酰胺环, 又不全影响酰胺侧链. 合成了二十个标题化合物, 其中九个被表明对β-内酰胺酶有抑制活性.     

3-烷基/芳基-6-(2', 4'-二氯苯基)-7H-1, 2, 4-三唑[3, 4-b]- 1, 3, 4-噻二 嗪的合成及波谱性质

以间二氯苯与氯乙酰氯反应,生成ω-氯代-2,4-二氯苯乙酮(1),再使之分别与3-烷基/芳基-4-氨基-5-巯基-1,2,4-三唑(2a～2l)反应,合成了12种新的3-烷基/芳基-6-(2',4'-二氯苯基)-7H-1,2,4-三唑并[3,4-b]1,3,4-噻二嗪(4a～4l)。利用EA,IR,^1HNMR确定了其结构,并提出该反应的可能机制。     

2-(N-三氟乙酰-N-三甲基硅烷基)氨基-3-三甲基硅烷氧基-羧酸三甲基硅烷酯和2-(N-三氟乙酰)-2,3-脱氢氨基酸的合成

利用三氟甲基磺酸三甲基硅烷酯, 我们合成了一种新的、化学活性很高的合成中间产物2-(N-三氟乙酰-N-三甲基硅烷基)氨基-1, 1-二(三甲基硅烷氧基)乙烯。脂肪醛或芳香醛发生碳碳成键的加成反应, 生成β碳原子上带有易离去基团三甲基硅烷氧基、N原子上带有保护基团三氟乙酰基的α氨基酸三甲基硅烷酯。消除反应得到了一个合成α、β脱氢氨基酸的可行途径。这类化合物是合成复杂多肽和肽生物碱的基元物。     

含硅芳香二酐的合成及其聚酰亚胺

从4-溴-l，2-二甲苯出发，经过三步反应合成了双-（3，4-苯二甲酸酐)二甲基硅烷单体，总产率为24．7％；由该单体与4，4′-二氨基二苯醚共聚合，经环化脱水反应得含硅聚酰亚胺，并对该共聚物进行了初步表征。     

Ti(OiPr)4/席夫碱配合物催化不对称2-甲氧基丙烯与对硝基苯甲醛的Hetero-ene反应

由新型联苯手性骨架(R)-( )-2-氨基-2′-羟基-6，6′-二甲基-1，1′-联苯la，(R)-( )-2-氨基-2′-羟基-4，4′，6，6′-四甲基-1，1′-联苯1b与不同取代基的水杨醛反应合成了9个新型席夫碱配体2a-2i，化合物的结构用核磁共振以及高分辨质谱进行表征．其中(R)-( )-2-氨基-2′-羟基-6，6′-二甲基-1，1′-联苯和3，5-二溴水杨醛衍生得到的席夫碱配体2g与Ti(O′Pr) 生成的配合物催化不对称2-甲氧基丙烯与对硝基苯甲醛的Hetero-ene反应，在-10℃反应3h时获得了最高为79?的反应产物．     

4-甲基-7，10-二氢苯并[h]香豆素的合成研究

以1-萘酚(6)为起始原料，经过Birch还原得到5，8-二氢-1-萘酚(7)；7与乙酰 乙酸乙酯在不同条件下缩合合成了4-甲基-7，10-二氢苯并[h]香豆素(4)．研究结 果表明，无氧和酸催化的反应条件对缩合反应是至关重要的．在没有酸催化的条件 下，反应生成3-乙酰基-2-羟基-6-甲基-吡喃-4-酮(8)，并通过单晶X射线衍射分析 确定了产物的结构；在酸催化的条件下，除了生成产物4外，还伴随生成脱氢芳构 化产物4-甲基苯并[h]香豆素(5)，而且在不同条件下二者的比例不同，其中以甲磺 酸为催化剂、在氮气保护下并加入抗氧化剂无水Na_2SO_3为最佳反应条件，化学选 择性约为70：30(4：5)，收率49．1％．     

由苯-1，2，4-三羧酸-1，2—酐和羟乙基哌嗪合成酰胺键、叔氨和酯键交替排列的水溶性超支化聚合物

基于官能团非等活性原理，由商品化多组分单体一步法合成了超支化聚合物． 用苯—1，2，4-三羧酸—1，2酐(BTAA)与羟乙基哌嗪(HEPZ)为原料，利用氨基和羟 基反应活性不同，制备了结构非对称超支化聚酰胺—酯．分别用红外、核磁共振确 定了所得聚合物的结构．该聚合物分子骨架中含有交替排列的酰胺键、叔氨和酯键 ，易溶于水．本合成方法原料易得、工艺简单，适合大量制备超支化聚合物．     

超急免疫排斥反应抑制相关寡糖二聚物的合成研究

首次报道了3,6-二氧代辛基-1,8-二-O-{4-O-[(3-O-a-D-吡喃半乳糖基)-β-D-吡喃半乳糖基]-2-脱氧-2-乙酰氨基-β-D-吡喃葡萄糖苷}(1)的合成，运用三氯乙酰亚胺酯法，通过控制反应条件，成功地实现了选择性、高收率地合成三糖PEG二聚物或其单苷化合物，并对成苷条件进行了深入的研究。     

二醇及氨基醇类鬼臼毒素衍生物的合成

以天然产物鬼臼毒素(1)为原料，合成了四种二醇及氨基醇类鬼臼毒素衍生物：4-O-乙基表鬼臼苦醇(4)，(1R,2S,3R,4S)-1-3',4',5'-三甲氧基苯基-2-氨甲基-3-羟甲基-4-乙氧基-6,7-亚甲二氧基-1,2,3,4-四氢萘(5)，(1R,2S,3R,4S)-1-3',4',5'-三甲氧基苯基-3-羟甲基-2-氨基-4-乙氧基-6,7-亚甲二氧基-1,2,3,4-四氢萘(6)和4-O-异丙基表鬼臼苦醇(7)。4～7及中间产物8～11都是新化合物。     

Design, synthesis, and properties of 2',4'-BNA(NC): a bridged nucleic acid analogue

The novel bridged nucleic-acid analogue 2',4'-BNA(NC) (2'-O,4'-C-aminomethylene bridged nucleic acid), containing a six-membered bridged structure with an N-O linkage, was designed and synthesized efficiently, demonstrating a one-pot intramolecular NC bond-forming key reaction to construct a perhydro-1,2-oxazine ring (11 and 12). Three monomers of 2',4'-BNA(NC) (2',4'-BNA(NC)[NH], [NMe], and [NBn]) were synthesized and incorporated into oligonucleotides, and their properties were investigated and compared with those of 2',4'-BNA (LNA)-modified oligonucleotides. Compared to 2',4'-BNA (LNA)-modified oligonucleotides, 2',4'-BNA(NC) congeners were found to possess: (i) equal or higher binding affinity against an RNA complement with excellent single-mismatch discriminating power, (ii) much better RNA selective binding, (iii) stronger and more sequence selective triplex-forming characters, and (iv) immensely higher nuclease resistance, even higher than the S(p)-phosphorthioate analogue. 2',4'-BNA(NC)-modified oligonucleotides with these excellent profiles show great promise for applications in antisense and antigene technologies.     

嘌呤N-6-吡啶盐中间体的形成及其在嘌呤核苷合成上的应用

本文报道以次黄苷为原料, 经酯化, 再在缩合剂4-氯苯磷酰二氯存在下与吡啶反应, 形成嘌呤N-6-吡啶盐中间体2, 该中间体2分别与碱性强弱不同的胺或氨及2moldm^-^3NaOH的醇溶液在室温反应, 可方便的合成6-NH2, 6-OCH3以及6-OCH2CH3-9-(β-D-呋喃核糖)嘌呤衍生物。并对以上产物形成的机制作了探讨。     

Kinetic preference for the 3'-5'-linked dimer in the reaction of guanosine 5'-phosphorylmorpholinamide with deoxyguanosine 5'-phosphoryl-2-methylimidazolide as a function of poly(C) concentration.

The formation of the internucleotide bond in diguanylate synthesis was studied in aqueous solution at pH 8 and 0.2 M Mg2+ in the presence and absence of polycytidylate, poly(C). The investigation was simplified by using guanosine 5'-phosphorylmorpholinamide, mor-pG, which can act only as a nucleophile, and deoxyguanosine 5'-phosphoryl-2-methylimidazolide, 2-MeImpdG, which can act only as an electrophile. The time-dependent product distribution was monitored by high-performance liquid chromatography (HPLC) and liquid chromatography mass spectrometry (LC/MS). In the absence of poly(C) the reaction between mor-pG and 2-MeImpdG yielded small amounts of the dimer mor-pGpdG with a regioselectivity of 2'-5':3'-5' = 3.5. In the presence of poly(C) dimer yields increased and a reversal in regioselectivity occurred; both effects were in proportion to the concentration of the polymer. The results can be quantitatively explained with the proposition that poly(C), acting as the template, catalyzes the reaction between template-bound monomers by about a factor of 4-5 over the reaction in solution and yields dimers with a regioselectivity of 2'-5':3'-5' approximately 0.33. These findings illustrate the intrinsic preference of guanosine monomers to correctly self-assemble on the appropriate template.     

重氮萘酮在环醚中热解反应研究

三种带有不同取代基的重氮萘酮(la～1c)在THF和二氧六环中加热分解给出不同的产物。1-重氮-4-萘酮(1a)的热解产物主要是重氮萘酮热解后产生的烯酮卡宾(2a)与环醚开环后形成的聚合物;3-甲基-1-重氮-4-萘酮(1b)的热解产物比较复杂,除冠醚类产物之外,还有烯酮卡宾对四氢呋喃和二氧六环的C-H键的插入反应产物、螺环化合物、2-甲基萘酚以及难以分离的聚合物;3-硝基-1-重氮-4-萘酮(1c)的热解产物主要是聚合物,此外还有少量C－H键的插入反应产物和2-硝基萘酚。对重氮萘酮热解反应的机理作了讨论。     

2-芳胺基-5-[5'-氨基-1'-(4"-氯苯基)-1',2',3'-三唑-4'-基]-1,3,4-噻二唑的合成

1-[5'-氨基-1'-(4"-氯苯基)-1,2,3-三唑-4'-甲酰基]-4-芳基-3-氨基硫脲在浓硫酸催化下环化得到2-芳胺基-5-[5'-氨基-1'-(4"-氯苯基)-1',2',3',-三唑-4'-基]-1,3,4-噻二唑2a-i, 依此法合成了九个标题化合物, 收率为30-74%。化合物2i的结构用X-光衍射单晶分析确证。     

Versatile three-component procedure for combinatorial synthesis of 2-aminospiro[(3'H)-indol-3',4-(4H)-pyrans

A convenient method of synthesis of substituted and annulated 2-amino-spiro[(3' H)-indol-3',4-(4 H)-pyrans] at mild conditions and in good yields is developed. Three component reaction of wide variety of substituted isatins, cyanoacetic acid derivatives, and carbonyl compounds or phenols gives the target compounds. Forty new spiropyrans were obtained, and their structures were proved by elemental analysis and 1H NMR and IR spectral data. It is shown that the use of a not very large set of starting compounds can lead to the synthesis of a thousand-member 2-amino-spiro[(3' H)-indol-3',4-(4 H)-pyran] library.     

Sequence- and regioselectivity in the montmorillonite-catalyzed synthesis of RNA

The possible role of catalysis in forming a limited number of RNAs from activated monomers is investigated by examining the sequence- and regioselectivity in the montmorillonite-catalyzed formation of RNA dimers and trimers. The reactivity of A was similar to that of G, and C was comparable in reactivity to U. Yet the reactivity of the purine nucleotides differed from that of the pyrimidines. In the reaction of nucleotides (pN) with activated monomers (ImpN), the sequence- and regioselectivity was Pu(3')Py > Pu(3')Pu = Pu(2')Py > Pu(2')Pu. The 5'-pyrimidine initiated dimers formed less efficiently than the 5'-purine initiated dimers. Trimer formation was investigated by the synthesis of 8 dimers (pNpN) and measuring the yields of trimers formed in the reaction of each dimer with a mixture of equal molar amounts of four activated monomers. The reactivity of the dimers depended on the nucleotide attached to the 3'-end of the RNA and the regiochemistry of the phosphodiester bond. Rules based on these studies are proposed to predict the sequence- and regioselectivity of the RNAs formed in montmorillonite-catalyzed reactions. These rules are consistent with the structures of the 2-5-mers formed in the reaction of equimolar amounts of ImpA and ImpC. This research establishes that the montmorillonite catalyst limits the number of RNA oligomer isomers formed. The potential significance of these findings to the origins of life is discussed.     

DAR青成色剂的合成

以1-羟基-N-[4-(2,4-二特戊基-苯氧基-丁基)-2-萘甲酰胺为母体,以2,5-二巯基-1,3,4-噻二唑为吸附基团,分别以1-甲酰基-2-(4-氨基)苯肼,1-乙酰基-2-(4-氨基)苯肼和1-三氟乙酰基-2-(4-氨基)苯肼为增强基团合成了3种DAR青成色剂。结构经IR、^1H NMR、MS及元素分析等检测确证。     

1-β-D-呋喃核糖基-1,2,4-三唑-3-酰胺铂(II)配合物的合成

在缓冲液中，利用1-β-D-呋喃核糖基-1，2，4-三唑-3-酰胺(ribavirin)和1- （2'-脱氧-β-D-呋喃核糖基）-1，2，4-三唑-3-酰胺(deoxyribavirin)作为配体 ，分别与cis-[Pt(DMSO)_2Cl_2]或K[Pt(DMSO)Cl_3]进行配位反应，得到了高产率 的[Pt-(N~4,N~7-ribavirin)(DMSO)Cl] (1)和[Pt(N~4,N~7-deoxyribavirin) (DMSO)Cl] (2)两种配合物。1-（2'-脱氧-β-D呋喃核糖基）-1，2，4-三唑-3-酰 胺的合成是由1-β-D-呋喃核糖基-1，2，4-三唑-3-酰胺与1，3-二氯-1，1，3，3- 四异丙基二硅氧烷保护，在1-甲基咪唑存在下与硫代苯氧基碳酰氯反应，再用tri- n-butyltin hydride和AIBN还原，四丁基氟化铵的四氢呋喃溶液脱去保护基四步反 应完成的。     

Electropolymerization of Pd(II) complexes containing phosphinoterthiophene ligands

A series of Pd complexes of 3'-diphenylphosphino-2,2':5'2' '-terthiophene (1a, dppterth) in which the metal is coordinated in three different modes have been prepared and electropolymerized, resulting in the formation of conductive thin films. In [Pd2(mu-Cl2)(dppterth-P,C3)2] (3a) the metal is P,C-coordinated, in [PdCl2(dppterth-P)2] (4a) the coordination is monodentate via the phosphine, and in [Pd(dppterth-P,C3)(dppterth-P,S1)][PF6] (5a) both P,C- and P,S-coordination modes are found. In 5a, the coordinated thiophene is hemilabile and may be displaced by reaction with more strongly coordinating ligands such as isocyanides. To probe the effect of blocking the alpha-position of the terthienyl moiety with methyl groups, 3'-diphenylphosphino-5-methyl-2,2':5'2' '-terthiophene (1b, Me-dppterth) and 3'-diphenylphosphino-5,5' '-dimethyl-2,2':5'2' '-terthiophene (1c, Me2-dppterth) were prepared, and the corresponding series of Pd complexes was synthesized. One of these complexes, [Pd(Me2-dppterth-P,C3)(Me2-dppterth-P,S1)][PF6] (5c), has been crystallographically characterized. The electropolymerized films prepared from 5a react with isonitriles, and shifts in the absorption spectra of the electropolymerized materials are observed upon reaction. A Pd complex has also been prepared from 5-diphenylphosphino-2,2':5'2' '-terthiophene (2, 5dppterth), and this complex has been electropolymerized. All the electropolymerized thin films have been characterized using EDX analysis, which demonstrates good correspondence with the elemental analysis of the respective monomers, and the maximum conductivities of the films are near 10(-4) S x cm(-1). Comparing the electropolymerization behavior of the complexes, along with their electrochemical and spectroscopic data, allows conclusions to be drawn regarding the involvement of pi-delocalization and the metal group in the conductivity of the materials.