Synthesis and biological evaluation of N-acetyl-beta-aryl-1,2-didehydroethylamines as new HIV-1 RT inhibitors in vitro

A variety of N-acetyl-o-aryl-1,2-didehydroethylamines were synthesized by direct reduction-acetylation of beta-aryl-nitroolefins and assayed as HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) for the first time. Compound 7a exhibited a TI v

Synthesis and anti-HIV-1 activities of novel podophyllotoxin derivatives

In order to explore the range of biological activities of the podophyllotoxin compound class, a novel series of derivatives of podophyllotoxin, which were conjugates containing stavudine and different structural podophyllotoxin analogues, were designed, s

Efficient One-Pot Synthesis of Highly Substituted Thiophene Library from 1,3-Dicarbonyl Compounds

A faccile and efficient one-pot synthesis of highly substituted thiophenes has been developed and employed for the preparation of a small focused library. Treatment of 1,3-dicarbonyl compounds 1 with CS2 in the presence of K2CO3 in DMF at room temperature, followed by stepwise addition of alkyl bromides 2 and methylene active bromides 3, provided via intramolecular cyclization 2,3,4,5-tetrasubstituted thiophenes 4 in yields of 77-94%. This protocol, combining construction and modification of the thiophene ring, increases the structural diversity of final products from readily available materials. A mechanism for the one-pot synthesis of thiophenes of type 4 has been proposed. A small focused library of thiophenes is prepared using the sequential addition of reagents to achieve unique substitution in the 2 and 5 position of the thiophene ring

Efficient and Divergent Synthesis of Fully Substituted 1H-Pyrazoles and

Efficient and divergent one-pot synthesis of fully substituted 1H-pyrazoles and isoxazoles from cyclopropyl oximes based on reaction conditions selection is reported. Under Vilsmeier conditions (POCl3/DMF), substituted 1H-pyrazoles were synthesized from 1-carbamoyl, 1-oximyl cyclopropanes via sequential ring-opening, chlorovinylation, and intramolecular aza-cyclization. In the presence of POCl3/CH2Cl2, substituted isoxazoles were obtained from the cyclopropyl oximes via ring-opening and intramolecular nucleophilic vinylic substitution (SNV) reactions

[4+2] Annulation - Convenient Synthesis of Substituted Dihydropyranones in Aqueous Media

A facile and convenient synthesis of dihydropyranones has been developed by a formal [4+2] annulation of readily available alpha-acetyl ketene S,S-acetals with various aldehydes, involving a tandem aldol reaction and conjugate addition-elimination reaction, in the presence of NaOH in water.

A Facile and Practical One-Pot Synthesis of beta-Oxo Thioamides from beta-Oxo Amides and Isothiocyanates

A facile and practical one-pot synthesis of beta-oxo thioamides from beta-oxo amides has been developed. By treatment with isothiocyanates in ethanol in the presence of potassium carbonate, a series of beta-oxo amides was converted, under reflux, in high yields into the corresponding beta-oxo thioamides.

Efficient synthesis of substituted tetrahydrothiopyrano[2,3-b]thiopyran-4,5-diones by a double annulation strategy from dialkenoylketene dithioacetals

An efficient synthetic procedure for substituted 2,3,6,7tetrahydrothiopyrano [2,3-b] thiopyran-4,5 -diones by a double annulation strategy is described. The ring systems are made in good yields from readily available dialkenoylketene dithioacetals in the presence of either sodium sulfide nonahydrate/N,N-dimethylformamide (DMF) or a sodium hydride/DMF/amine system.

Microwave-assisted synthesis of high-molecular-weight poly(ether imide)s by phase-transfer catalysis

A facile and rapid polycondensation reaction of disodium bisphenol A with bis(chlorophthalimide)s was preformed with a domestic microwave oven in o-dichlorobenzene by phase-transfer catalysis. The polymerization reactions, in comparison with conventional heating polycondensation, proceeded rapidly and were completed within 25 min. The polymerizations gave the corresponding poly(ether imide)s with inherent viscosities of 0.55-0.92 dL g(-1). The effects of various factors on the polymerization, such as the amount of the catalyst, the reaction time, and the microwave power were studied. The properties of the polymers were briefly characterized.

A rapid solid-phase synthesis to soluble oligothiophene molecular wires

A novel method for the preparation of oligothiophene molecular wires is described via a bi-directional solid-phase synthesis. Using an alternating sequence of bromination and Stille coupling reactions, oligomers were obtained up to the heptamer in excellent yield and purity.

Studies on synthesis, structure and biological activities of novel triazole compounds containing thioamide

Four novel triazole compounds containing thioamide group were designed and synthesized by using triazole, phenyl isothiocyanate and aryl ethyl ketone as raw material. Their structures were conformed by elemental analysis, H-1 NMR, IR and MS spectra. The crystal structure of 1-[1-anilinothiocarbonyl-1-(4-fluorobenzoyl)methyl]-1,2,4-trizole has been determined by X-ray diffraction analysis. The preliminary bioassays have shown that the title compounds exhibit certain antifungal activity.

磁性纳米颗粒负载催化剂的制备及其在有机合成中的应用

过去的几十年，纳米科学在材料、医药、生物、催化等领域得到极其广泛的应用。由于在尺寸上的优势，使用纳米材料作为催化剂载体，可以使异相催化剂均相化，从而提高催化剂的活性和选择性。近年来，磁性纳米颗粒由于其容易分离的特点而作为催化剂载体受到广泛关注。鉴于此，本论文着眼于设计合成一系列磁性纳米颗粒负载的催化剂并研究其在一些有机化学反应中的应用，并进一步研究其重复使用情况。 本论文的主要内容包括以下几个部分： 1．制备了一系列磁性纳米颗粒固载的季胺盐和季膦盐，并将其应用到由二氧化碳和环氧化合物制备环状碳酸酯的反应中，详细研究了温度、催化剂用量、压力等条件对反应的影响，并进一步研究了催化剂的分离和重复使用情况。 2. 合成了二（2－吡啶基）－甲醇，通过Click反应将其固载到磁性纳米颗粒表面并与Pd进行配位，并将其应用于Suzuki和Sonogashira交叉偶联反应中，研究了不同溶剂和反应条件对反应的影响，并讨论了该催化体系的重复利用性能。 3. 合成了一系列的树枝状大分子负载的Click型有机催化剂，并将其用于酮对芳香硝基乙烯化合物的不对称Michael加成反应中。分别研究了在水相和无溶剂条件下反应进行的情况，并研究了催化剂的重复使用情况。 4. 制备了一系列磁性纳米颗粒负载的树枝状大分子催化剂，并应用于环己酮对芳香硝基乙烯化合物的不对称Michael加成反应中。研究了树枝状大分子的代数对催化剂活性的影响，并讨论了催化剂的分离和重复使用情况。

有机质谱裂解规律及智能解析方法研究

本学位论文分为四个部分，第一部分报道了用串联质谱快速分析合成药物中的微量杂质成分以及分析中药材中的化学成分。第二部分报道了通过质谱和串联质谱发现并合成新型的PdPincer 催化剂，同时对其活性进行测试。第三部分为串联质谱自动解析软件的设计及应用。第四部分概述了应用在质谱中的各种碎裂方式。 第一部分首先总结了5-溴粉防己碱及其类似物的裂解规律，并以此为根据推测出2 个微量杂质的结构。随后针对无患子（Sapindus mukurossi Gatren.）中的皂苷成分，由ESI-QTOF 得到各个皂苷成份的高分辨质量数据进而得到其分子式，然后利用ESI-IT 电喷雾串联质谱对无患子总皂苷中各皂苷成分的结构进行进一步的鉴定。进而以同样的方式，先通过ESI-QTOF 得到黄山药（Dioscoreapanthaica）总皂苷中各个组分化合物的分子式，然后对已有的薯蓣皂苷标准品做串联质谱分析，以得到该类化合物的裂解规律并给出解析该类化合物的流程图。在此利用计算化学的方法讨论了离子的丰度与裂解活化能之间的关系。然后应用APCI-MS/MS 方法探讨了四对同分异构体和几个已知的化合物，并最后用液质联用对其进行确认，同时还给出了4 个未知化合物的可能结构。 第二部分报道通过质谱和串联质谱发现并合成新型的PdPincer 催化剂，同时对其活性进行测试。钯催化的交联反应是有机合成中C-C 键形成的最有效的方法，且硫脲是一类对空气和水都稳定的化合物，因此我们设计并合成了一系列的硫脲钯催化剂并得到了很好的催化活性。我们在对其中一类环状双硫脲化合物进行质谱实验的时候，在正离子模式下发现了反常的[M.H]+，通过串联质谱进一步确定了它是一种新型的PdPincer 结构。我们将其合成出来并通过X-ray 衍射实验确定了它的结构。同时测定其催化活性并与未形成pincer 的类似物进行比较发现该类化合物具有较宽的底物适用性。 第三部分为串联质谱自动解析软件的设计及应用。通过前面两部分的启示，独立设计开发了AuMass（1.0）。其算法是：先通过查找特殊的碎片离子，中性丢失或碎片离子质量差来确定某类化合物的骨架结构，然后利用该类化合物的自动解析流程来对其周边取代基进行确认。通过它快速地对白芍中的化学成分进行解析，并对未知的化合物进行了推测。为了增加它的解析能力，我又对其它类型的化合物裂解规律进行总结，并给出了自动解析流程。实践证明该软件具有相当好的应用价值。 第四部分综述了应用在质谱上的各类母离子的碎裂技术。这里包括了碰撞诱导裂解（CID）、光诱导碎裂（LID）、电子捕获裂解/电子转移裂解（ECD/ETD）、红外多光子解离（IRMPD）、黑体辐射解离（BIRD）和PQD 裂解技术。 This dissertation consists of four chapters. The first chapter reports the rapidanalysis of trace impurities from synthetical medicine and analysis of the chemicalconstitutents from Chinese herb medicines. The second chapter elaborates the studieson the discorvery and synthesis of new type of Pd Pincer catalyst by using MS andtandem MS together with the testing of its catalyst activity. The third chapter dwellson the designation and development of automatic tandem mass spectrometry analysissoftware. The last chapter presents a review on the dissociation technique of massspectrometry. The first chapter reports the rapid analysis of trace impurities from synthesismedicine and analysis of the chemical constitutents from Chinese herb medicines. The fission mechanism of 5-bromotetrandrine was obtained by analysis of the dissociationpathways of major product, by using which the possible structure of the two traceimpurties was assumed. There are lots of saponins in Sapindus mukurossi. Except forthe good spumescence and decontamination，it possesses the bioactivity of antigenand antitch. First of all, the high resolution mass information was obtained by ESI-QTOF. Hence the possible molecular formulars were acquired too. Then weconducted the further detection of the structures of its saponins by using ESI-ITtechnology. In the same manner, first the molecular formulars of every constituentfrom Dioscorea panthaica in total saponins were obtained by ESI-QTOF, and thenacquired the fission mechanism of this type of compounds by tandem massexperiment on a series of known and available saponins. In the same time, theanalysis flowchart was concluded. Here the relationship between the ion intensity andthe corresponding dissiociation activation energy was studied by computer chemistry.Then the four pairs of isomers were differentiated by APCI-MS/MS, as well as thecharacterization of known and unknown compounds. The assumption was confirmed by HPLC-MS/MS. Among them the possible structures of four unknown saponinswas presented. The second part was discovery and synthesis of a new type of Pd pincer catalystby MS and tandem MS. The coupling reaction catalyzed by Pd is the most effectivemethod in C-C formation in organic synthesis. Apart from that, thiourea is type ofcompounds that are stable to atmosphere and moisture. Hence we designed a series ofPd thiourea catalysts. Some of them show the excellent catalyst activity. The abnormalparent ion [M.H]+ was founded in positive ESI mode when we conduct some massspectrometry experiments on the bicyclical thiourea Pd complex. The structure wasproposed by mass and tandem mass spectrometry. Because it was a new type of pincer,we want to test its catalyst activity. So the Pd pincer was synthesized and the detailstructure was obtained by x-ray experiment. It shows the more fitness in catalysis ofSuzuki reaction by comparison with the analogue. The third chapter dwells on the design and development of automatic tandemmass spectrometry analysis software. Inspired by the former two chapters, theAuMass (version 1.0) was developed. Its algorithm is: first check the diagnostic ion,diagnostic neutral loss or diagnostic ions mass intervals in database to find out whatthe analyst’s skeleton belongs to, then identify the peripheral functional group by thecorresponding analysis flowchart. The chemical constituents of Paeonia lactiflorawere identified rapidly by using AuMass. To increase the analysis ability, the othertypes of compounds from Chinese herbs was concluded. Actually, the software isproven to have the much valuable application. The last chapter presented the review on the some kinds of fission technique ofmass spectrometry. It involves the collision induced dissociation (CID), laser induceddissociation (LID), electron capture dissociation/electron transfer dissociation(ECD/ETD), infrared multiple photons dissiociation, black body irraditiondissociation and PQD fission technique from Finnigan.

Ring-Enlargement of Dimethylaminopropenoyl Cyclopropanes: An Efficient Route to Substituted 2,3-Dihydrofurans

A convenient and efficient synthesis of substituted dihydrofurans is developed via ring-enlargement of 1-dimethylaminopropenoyl-1-carbamoyl/benzoyl cycloproparres catalyzed by ammonium acetate in acetic acid with high regio- and stereoselectivity. Some of the newly synthesized substituted dihydrofurans are subjected to further synthetic transformation in the presence of NaOH (aq) in ethanol to afford the corresponding 5-aryl-2,3-dihydrofuro[3,2-c]pyfidin-4(5H)-ones in high yields.

Bronsted guanidine acid-base ionic liquids: Novel reaction media for the palladium-catalyzed Heck reaction

Bronsted acid-base ionic liquids (GILs) based on guanidine and acetic acid are efficient reaction media for palladium-catalyzed Heck reactions. They offer the advantages of high activity and reusability. GIL2 plays multiple roles in the reaction: it could act as solvent, as a strong base to facilitate beta-hydride elimination, and as a ligand to stabilize activated Pd species.