Dissertations / Theses on the topic 'Bicyclo[2.2.1]heptane'

Chemical modifications of oligonucleotides provide an important tool to understand how the natural substrate works as well as how to improve their biochemical and biological properties as potential therapeutics and diagnostics. Our carba-LNA (2',4'-carba-bridged Locked Nucleic Acid) modified oligo-DNA or -RNA have been found to be useful to modulate oligo-RNA and -DNA activity. This thesis is based on four papers: Paper I (J. Org. Chem. 2010, 75, 7112-7128) deals with the synthesis of 2',4'-propylene-bridged (Carba-ENA) thymidine and its analogues. These carba-ENA nucleosides have been subsequently incorporated into 15mer antisense oligodeoxynucleotides (AON), and their affinity toward complementary mRNA and DNA, as well as their nuclease resistance and RNase H recruitment capability have been investigated in comparison with those of the native and ENA counterparts. Paper II (J. Org. Chem. 2012, 77, 6855–6872) illustrates the synthesis of dimethylbicyclo[2.2.1]heptane and a diastereomeric mixture of oxabicyclo[2.2.1]heptanes by the free-radical ring-closure reaction approach. The role of steric factors for different chair- and the boat-like transition states was evaluated involving the 5-exo radical ring closure reaction to a tethered olefin. Paper III (J. Org. Chem. 2012, 77, 9747-9755) shows an unusual strain releasing reaction of 1-mesyloxy-8,7-dimethylbicyclo[2.2.1]heptane by a base-promoted substitution at the chiral C3 followed by spontaneous concerted ring opening involving the most strained C2-C3-C4 bonds (with bond angle 94°) and the C2 bridgehead leading to anti-endo elimination of the C1-mesyloxy group by the conjugate base of adenine or thymine to give two diastereomeric C3'(S) and C3'(R) derivatives of 1-thyminyl and 9-adeninyl cyclohexene, and a mechanistic rational has been formulated. Paper IV (J. Org. Chem. 2014, 79, 7266−7276) focuses on the diastereospecific synthesis of E/Z bicyclo[2.2.1]heptane-7- and oxabicyclo[2.2.1]heptane-8-oximes and their corresponding C-nitroso derivatives. The comparative kinetic and thermodynamic studies of the conversions of the C-nitroso side products to the required oximes have been delineated leading to the synthesis of desmethyl sugar derivatives.

Epibatidine (exo-2-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane) is an alkaloid isolated from the skin of the Ecuadorian poison frog. It has been known since 1992 and has high binding affinity for nicotinic acetylcholine receptors. Many studies have reported epibatidine to possess analgesic properties, but it is also toxic even in low doses, thus, it cannot be used therapeutically. A wide range of epibatidine analogues have been studied in the hope of reducing their toxicity, and hence exploiting their therapeutic potential A general method for the synthesis of anti-7-functionalised 2-benzyl-2-azabicyclo[2.2.1]heptane has been employed. Aza Diels-Alder reaction was used successfully to construct the rigid protected amine 2-benzyl-2-azabicyclo[2.2.1]hept-5-ene skeleton. Bromination of 2-benzyl-2-azabicyclo[2.2.1]hept-5-ene gives a reactive tricyclic salt, which in turn undergoes skeletal rearrangement with hydrid to obtain anti-7-bromo-2-benzyl-2-azabicyclo[2.2.1]heptane. Nucleophilic substitution reaction at C-7 of this compound found to be occur with retention of configuration, consistent with neighbouring group participation of the bicyclic nitrogen lone pair. An oxidation-reduction strategy facilitated the epimerisation at the C-7 of 2-azabicyclo[2.2.1]heptane, heterocycles have been introduced at this position to give the ether linkage nicotinic receptor ligands with general structure 7-(pyridyloxy)-2-benzyl-2-azabicyclo[2.2.1]heptane. Mitsunobu chemistry has been utilised to synthesis a range of pyridyl ether compounds. Methylisoxazole heterocycle has also been synthesised and incorporated to open the way to some analogues. The synthesis of fluorinated analogues of 2-azabicyclo[2.2.1]heptane has been investigated using nucleophilic fluorinating agent, diethylaminosulphur trifluoride, DAST. Moreover, fluorination of all alcohols is consistent with SN2 attack, whilst fluorination of ketones gave geminal difluorides with the 6-oxo isomer being assisted by neighbouring group participation. A range of different 5- and 6-chloropyridyl-substituted-2-azabicyclo[2.2.1]heptane derivatives have been constructed. The 5- and 6-chloropyridyl derivatives were synthesised via nucleophilic attack of lithiated-chloropyridine onto the appropriate azabicyclic ketone. Dehydration of the adduct gave an olefin. 1H, 13C and 19F NMR spectroscopy was used to characterise these compounds.

On examine deux approches synthetiques. La premiere voie met a profit le rearrangement en milieu acide de derives selenies obtenus au depart du geraniol. Les seleno-alcools obtenus sont transformes en bicycloethers cherche par deux voies distinctes. Cependant cette voie mene aux derives de type endo qui ne sont pas de type naturel. La seconde approche se rapporte au rearrangement des epoxydes terminaux par emploi des acides de lewis, tel sncl::(4) le plus adapte aux isomerisations souhaitees. Apres avoir mis au point cette sequence, le travail se divise en deux directions: recherche d'une voie d'homologation pour passer aux derives sesquiterpeniques par addition, d'une unite isoprenique (synthese convergente), preparation directe de l'epoxy-3'6' auraptene soit en serie racemique, soit en serie optiquement active par l'intermediaire d'un epoxyde de configuration 3r. Dans ce dernier cas on obtient le compose nature. Un diagramme ortep issu d'une etude par rayons x d'un monocristal de ce compose permet de definir la stereochimie sans ambiguite, ce qui n'avait jamais ete realise a ce jour dans cette serie dont la configuration absolue du centre d'asymetrie est 3r. Enfin par conversion enantiomerique et passage par la (+)-marmine, on accede a la serie de chiralite inverse. Les principaux objectifs ont donc ete atteints

Nous reportons dans ce manuscrit une etude de la substitution nucleophile (sn) des diastereoisomeres endo et exo du bicyclo-(1,2,2) heptane-2 ol et de ses derives acetates, benzoates et benzoates parasubstitues, induit sous ionisation chimique a l'ammoniac dans la source haute pression d'un spectrometre de masse triplequadrupolaire. Les mecanismes de substitution nucleophile sont determines en comparant les spectres cad des ions de substitution nucleophile m#sh#+ avec ceux des ions de protonation mh#+ des amines de stereochimie correspondantes obtenues par synthese. Nous avons ainsi pu definir que le borneol, l'isoborneol, l'endoborneol et l'exonorborneol conduisent a une retention de configuration lors de la substitution nucleophile suivant un mecanisme intramoleculaire de type s#ni. Les diastereoisomeres endo et exo des acetates, benzoates et benzoates parasubstitues du borneol et du norborneol conduisent lors de la substitution nucleophile a un ion m#sh#+ de structure commune correspondant a celle de l'amine de configuration exo. Les isomeres endo reagissent donc suivant un mecanisme s#ni. Differents intermediaires sont proposes pour expliquer ces orientations stereospecifiques. L'etude de collisions reactives avec nh#3 dans la cellule de collisions a permis de confirmer les mecanismes de s. N. Et mis en evidence le comportement particulier des ions m#sh#+ de l'acetate de l'endonorborneol et de l'acetate de l'isoborneol. Un mecanisme est propose

The focus of the research described in this section of the thesis is the synthesis of compounds expected to bind strongly to both the estrogen β and α receptors and act as estrogen agonists. Based on earlier results in our group and docking studies we prepared a series of A-CD analogs, compounds 1, in which the usual 13-methyl group was replaced by an ethyl group. Docking studies also indicated that substituents at C8 could lead to enhancement of binding to the estrogen receptor. With this in mind two such derivatives, compounds 2 were prepared. A major concern in the use of estradiol in hormone replacement therapy is its potential metabolism of dangerous ortho-quinones. The 1,2-naphthalenediol derivatives 3 avoid this possibility. They were predicted to be potent binders to the estrogen receptors with the naphthalene diol portion serving as rings A and B and the hydroxyl group taking the place of the 17-OH group of estradiol. The preparation of several derivatives of 2 is reported. The estrogen receptor binding [ERB] relative to estradiol as standard has been determined at the University of Illinois for a number of the compounds prepared in this thesis. Unfortunately, the results were not as encouraging as expected. Importantly, all of the 13-ethyl derivatives tested showed lower binding affinity compared to the 13-methyl analogs. Similarly, the derivatives with substituents at C8 do not show higher activity than those having only hydrogens at C8. Finally, the situation with the naphthalene derivatives is, at this stage, still not completely resolved. The binding for the compounds thus tested is quite low, but it must be admitted that the structures thus far synthesized have a much lower LogP than estradiol, a factor known to greatly decrease the binding constants to the estrogen receptors.

En les darreres dècades, l’ús d’anàlegs de nucleòsids (ANs) ha despertat un gran interès de recerca per a la teràpia antiviral i anticancerigen. La conformació i el plegament de la unitat de sucre dels nucleòsids tenen un paper crític en la modulació de la seva activitat biològica. En aquest context, s’han dissenyat i sintetitzat nous anàlegs de carbanucleòsids (ACNs) restringits conformacionalment per imitar el comportament conformacional de l’anell de furanosa natural. Els nucleòsids ciclohexenílics són un tipus prometedor de compostos antivirals, en què la substitució de l’àtom d’oxigen de l’anell de furanosa per un doble enllaç indueix una flexibilitat anular, similar a la dels nucleòsids naturals. Recentment, s’ha descrit que ambdós enantiòmers del ciclohexenil G (DCG i LCG) mostren una potent i selectiva activitat antivirus. Tenint en compte la interessant activitat anti-HSV del ciclohexenil G, es va proposar una nova sèrie d’ANs biciclo[4.1.0]heptà al nostre grup de recerca, en què el doble enllaç va ser substituït per un ciclopropà fusionat. La present tesi doctoral està enfocada a la síntesi enantioselectiva d’una nova sèrie d’ANs carbocíclis de sis membres basats en l’esquelet del ciclohexenil G que conté la unitat de biciclo[4.1.0]heptà. Concretament, es descriu l’assoliment dels objectius següents: - En primer lloc, s’han optimitzat dues estratègies sintètiques desenvolupades en el nostre grup de recerca per preparar la cetona clau 36, que és l’intermedi comú per a la preparació dels ANs biciclo[4.1.0]heptà. La cetona 36 s’ha obtingut en una seqüencia de 6 passos robusta, reproduïble i eficaç a escala de multi-gram amb un rendiment total del 49% a partir de l’1-ciclohexadiona. -En segon lloc, ja que els ANs 5-hidroximetilbiciclo[4.1.0]heptà, BCH-(A, G, T i U), prèviament obtinguts al grup de recerca, no mostraven activitat antiviral significativa, es va decidir de completar la família de 5-hidroximetilbiciclo[4.1.0]heptà, on es va sintetitzar l’anàleg de citosina que es va obtenir amb un rendiment total del 4% en 17 etapes. Tot i això, no va presentar activitat antiviral ni citotoxicitat. Tota aquesta família de ANs han estat avaluades en assajos enzimàtics per determinar l’afinitat amb la timidina quinasa (TK) vírica. El compost basat en timidina BCH-T té una interessantíssima afinitat cap a HSV-TK (EC50 = 1.6 ± 0.1 µg / ml), que coincideix amb el nostre model computacional realitzat per a la primera etapa de fosforilació per aquests productes. -En tercer lloc, s’ha preparat una nova família d’ANs 5-hidroximetil-4-hidroxibiciclo[4.1.0]heptan-2-il. En particular, els ANs de timina i guanina s’han obtingut en 17 i 18 passos i amb un rendiment global del 18% i 10%, respectivament. L’epímer-C4 de la timina i l’alquè de la timina 4,5-é s’han sintetitzat en 19 etapes i un rendiment total del 6% i del 3%, respectivament. Aquests quatre ANs han estat avaluats per determinar la seva activitat antiviral, encara que cap d’ells mostra cap activitat significativa. -Finalment, també s’ha obtingut una nova família d’ACNs 1,2,3-triazole-biciclo[4.1.0]heptà. Aquest enfocament ha permès la preparació de quatre compostos 1,2,3-triazol-ACNs (4-substituït) via CuAAc amb un rendiment global del 19-16% en 15 etapes. A més, es va obtenir un compost 4,5-substituït mitjançant una reacció de cicloaddició i un 12% de rendiment en 14 etapes. S’ha avaluat l’activitat biològica d’aquests anàlegs contra diversos virus, tot i que només el propilbenzen-1,2,3-triazolo-ACNs 151 mostra una activitat considerable contra el virus Coxsackie B4 (EC50 = 13.5-9.4 µg / mL).
En las últimas décadas, el uso de análogos de nucleósidos (ANs) ha generado un amplio interés de investigación para la terapia antiviral y anticancerígena. La conformación y el plegamiento de la unidad de azúcar de los nucleósidos juegan un papel crítico en la modulación de su actividad biológica. En este contexto, se han diseñado y sintetizado nuevos análogos de carbanucleósidos (ACNs) restringidos conformacionalmente para imitar el comportamiento conformacional del anillo de furanosa. Los nucleósidos de ciclohexenilo son un tipo prometedor de compuestos antivirales, donde el reemplazo del átomo de oxígeno del anillo de furanosa por un doble enlace induce flexibilidad anular, similar a la de los nucleósidos regulares. Recientemente, se ha descrito que ambos enantiómeros de ciclohexenilo G (DCG y LCG) muestran una actividad potente y selectiva contra el virus del herpes (HSV). Teniendo en cuenta la interesante actividad anti-HSV del ciclohexenilo G, en nuestro grupo de investigación se propuso una nueva serie de ANs biciclo[4.1.0]heptano en el que el doble enlace fue reemplazado por un ciclopropano fusionado. La presente Tesis doctoral se centra en la síntesis enantioselectiva de una nueva serie de ANs carbocíclicos de seis miembros basados en el esqueleto del ciclohexenilo G conteniendo la estructura de biciclo[4.1.0]heptano a partir de un intermedio clave común. Específicamente, se describe el logro de los siguientes objetivos: - En primer lugar, se han optimizado dos estrategias sintéticas desarrolladas en nuestro grupo de investigación para preparar la cetona clave 36, que es el intermedio común para la preparación de los ANs biciclo[4.1.0]heptano. La cetona 36 se ha obtenido en un secuencia robusta, reproducible y eficiente de 6 pasos en una escala de multi-gramo con un rendimiento general del 49% a partir de 1,4-ciclohexadiona. -En segundo lugar, dado que los análogos 5’-hidroximetilbiciclo[4.1.0]heptano BCH-(A, G, T y U), obtenidos previamente en el grupo de investigación, no mostraron actividad antiviral significativa, se decidió completar la familia 5’-hidroximetilbiciclo [4.1.0]heptanilo sintetizando el análogo de citosina que ha sido obtenido con un rendimiento global del 4% en 17 pasos. Sin embargo, no mostró actividad antiviral o citotoxicidad. Toda esta familia de AN se ha evaluado en ensayos enzimáticos para determinar la afinidad de la timidina quinasa (TK) vírica. El compuesto a base de timidina BCH-T tiene una gran afinidad interesante hacia HSV-TK (EC50 = 1.6 ± 0.1 µg/mL) que es consistente con nuestro modelo computacional realizado para la primera etapa de fosforilación para estos compuestos. -En tercer lugar, se ha preparado una nueva familia de ANs 5’-hidroximetil-4’-hidroxibiciclo[4.1.0]heptan-2’-ilo. En particular, se obtuvieron los ANs de timina y guanina en 17 y 18 pasos y un rendimiento general de 18% y 10%, respectivamente. El epimero-C4 de timina y el alqueno de timina 4’,5’-eno se han sintetizado en 19 pasos y con un rendimiento general de 6% y 3%, respectivamente. Estos cuatro AN han sido seleccionados para evaluar su actividad antiviral, aunque ninguno de ellos muestra actividad significativa. -Finalmente, también se ha obtenido una nueva familia de ACNs 1,2,3-triazol-biciclo[4.1.0]heptanilo. Este enfoque ha permitido la preparación de cuatro 1,2,3-triazolo-ACNs (4-sustituido) a través de CuAAc con un rendimiento global del 19-16% en 15 pasos. Además, también se ha sintetizado un compuesto de triazol (4,5-sustituido) mediante una reacción de cicloadición y 12% de rendimiento en 14 etapas. Se ha evaluado la actividad biológica de estos análogos contra varios virus, aunque solo el propilbenceno-1,2,3-triazolo-ACN 151 muestra una actividad considerable contra el virus Coxsackie B4 (EC50 = 13.5-9.4 µg/mL).
In the last decades, the use of nucleoside analogues (NAs) has garnered extensive research interest for antiviral and anticancer therapy. The conformation and puckering of the sugar moiety of nucleosides play a critical role in modulating their biological activity. In this context, new conformationally restricted carbanucleosides analogues (CNAs) have been designed and synthesised in order to mimic the conformational behaviour of the natural furanose ring. Cyclohexenyl nucleosides are a promising type of antiviral compounds, wherein replacement of the oxygen atom of the furanose ring by a double bond induces annular flexibility, similar to that of regular nucleosides. Recently, it has been described that both enantiomers of cyclohexenyl G (DCG and LCG) display potent and selective anti-herpes virus activity. Considering the interesting anti-HSV activity of cyclohexenyl G, new series of enantiopure bicyclo[4.1.0]heptanyl NAs were proposed in our research group, in which the double bond was replaced by a fused cyclopropane. The present Ph.D Thesis is focused on the enantioselective synthesis of a novel series of six-membered carbocyclic NAs based on the skeleton of cyclohexenyl G containing bicyclo[4.1.0]heptane structure from a common key intermediate. Specifically, it is described the achievement of the following objectives: - Firstly, two synthetic strategies developed in our research group have been optimized in order to prepare the key ketone 36, which is the common intermediate for the preparation of bicyclo[4.1.0]heptane NAs. Ketone 36 has been obtained in a robust, reproducible, and efficient 6-steps approach on a multigram scale in 49% overall yield from commercially available 1,4-cyclohexadione. -Secondly, since the 5’-hydroxymethylbicyclo[4.1.0]heptane analogues BCH-(A, G, T and U) NAs, previously obtained in the research group, did not show significant antiviral activity, in order to complete the 5’-hydroxymethylbicyclo[4.1.0]heptanyl family, the cytosine analogue has been synthesised in 4% overall yield in 17 steps. However, it does not show antiviral activity or cytotoxicity. All of this family of NAs have been evaluated in enzymatic assays in order to determine the virus-TK affinity. The thymidine-based compound BCH-T has an interesting great affinity towards HSV-TK (EC50 = 1.6 ± 0.1 µg/mL) which is consistent with our computational model performed for the first stage of phosphorylation. -Thirdly, a novel family of 5’-hydroxymethyl-4’-hydroxybicyclo[4.1.0]heptan-2’-yl NAs has been prepared. In particular, thymine and guanine NAs have been obtained in 17 and 18 steps and 18% and 10% overall yield, respectively. The thymine C4-epimer and the thymine alk-4,5-ene have been synthesised in 19 steps and 6% and 3% overall yield, respectively. These four NAs have been screened for antiviral activity, although none of them show significant activity. -Finally, a new family of 1,2,3-triazolo-bicyclo[4.1.0]heptanyl CNAs has also been obtained. This approach has allowed the preparation of the four 4-substituted-1,2,3-triazolo-CNAS via CuAAc in 19-16% overall yield in 15 steps. Furthermore, the 4,5-substituted-1,2,3-triazolo-CNAS has been synthesised via cycloaddition and 12% yield in 14 steps. The biological activity of these analogues against several viruses has been evaluated, although only the propylbenzene-1,2,3-triazolo-CNAs 151 shows a considerable activity against Coxsackie B4 virus (EC50 = 13.5-9.4 µg/mL).

碩士
國立中正大學
化學所
96
The anhydrides 28, 29 used as starting materials were made from 2,3-dicyanohydroquinone via a series of treatments, such as oxidation, Diels-Alder cycloaddition, enolization, methylation, hexylation, basic hydrolysis, and acidic dehydration. Then, we used diamino -bipyridine 4,4’-diamino-2,2’-bipyridine (39) and 5,5’-diamino-2,2’-bipyridine (35) which were syntheses by ourself to react with the anhydrides 28, 29 and to give imide products 42, 43, 44, 45. In the X-ray diffraction characterization of compound 45, we observed the methylenes on the bridges were trans to one another, and the bipyridine planes of the imide compound 45 were coplanar with one another. Between these molecules exist the π-π interaction, and we may estimate that the observed conformations of compound 45 correspond to most steady energetic requirements for crystalline packings. The photophysical and metal ion-sensing properties of these products were examined in acetonitrile. The changes in fluorescence and ion selectivity of each product were found to be similar to one another. 42 and 43 were capable of detecting copper ion by showing dramatic quench of fluorescence. From the experiments, we can found that the bipyridyl imides can be complexing well with copper ion and detecting the changes by using the fluorescence. The bipyridyl compounds can be a good chemosensor for copper ion.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1987.
Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

The Norrish/Yang photochemistry of two series of norbornane derivatives, 7-methyl-7- benzoylnorbornanes and 7-benzoylbenzonorbornenes, has been studied in both the solid state and solution. In the 7-benzoylbenzonorbornene system, photolysis in the solid state leads to a significant alteration in the ratio of photoproducts, from a complex mixture of two Yang cyclobutanols and a Norrish type II cleavage product in solution, to a single product, an endo-aryl cyclobutanol, in the solid state due to the confining effects of the crystal lattice. Photolysis of the 7-methyl-7-benzoylnorbornanes in the solid state or solution led to formation of an endo-aryl cyclobutanol as the sole photoproduct. By utilizing ionic chiral auxiliaries it was possible to form chiral ammonium carboxylate salts between optically pure amines and the achiral norbornane derivatives containing a carboxylic acid functional group. Photolysis of the chiral salts in the solid state gave variable results, but through the use of a number of auxiliaries it was possible to achieve a high degree of enantioselectivity in the photoproducts (up to 98% ee at 100% conversion of the starting ketone). Photolysis of the same salts in solution gave only a racemic mixture of photoproducts, highlighting the critical role that the chiral crystal lattice plays in the asymmetric induction. Through the use of X-ray crystallography, solid state reactivity-crystal structure relationships were developed to explain the observed reactivity in 11 of the ketone substrates. Fortuitously, two of the molecules studied underwent single crystal-to-single crystal reactions, allowing for a detailed study of the reaction through a series of X-ray crystal structures. In this case, because the molecules studied were chiral ammonium carboxylate salts used in the asymmetric induction studies, it was possible to predict and confirm the absolute configuration of the photoproduct, as well as validate the crystal structure-reactivity relationships. Comparison of the results obtained in the studies presented have also been compared to previous work in order to develop a greater understanding of how conformational changes in the geometry of a ketone can affect the outcome of Norrish/Yang reactions.

Part I. Several azoalkane-triplet sensitizer bichromophoric systems are synthesized and the energy transfer properties are studied. Intramolecular energy transfer to azoalkanes is found to be much slower than literature cases with aromatic hydrocarbon acceptors. This is the first study of intramolecular energy transfer to a small chromophore. Energy transfer efficiencies are studied by measurement of phosphoresence intensities and lifetimes in low temperature glasses. Polymethylmethacrylate is used as a rigid matrix for some emission studies. Competitive intra and intermolecular quenching experiments and the corresponding Stern-Volmer plots are used to determine energy transfer rates in solution. Eventually a bichromophoric system (AP-DBO) is synthesized that has both the desired rapid intramolecular energy transfer and a quenchable azo triplet lifetime of (TURN)7 ns. Attempts to observe the azo triplet by transient techniques are unsuccessful. The triplet energies of several azos are estimated by kinetic spectroscopy using a graded series of sensitizers and the singlet-triplet energy gap is found to be constant at about 20 kcal/mol. Part II. The photochemical isomerization of azo-1-bicyclo 2.2.1 heptane is studied on long and short wavelength irradiation. Long wavelength irradiation yields (PHI)(,c(--->)t) = (PHI)(,t(--->)c) = 0.5. Isomerization quantum yields on 193 nm irradiation from an ArF laser are much lower than 0.5 and some deazatization occurs. An energy level diagram is presented to account for the observed results. Attempts are made to determine the triplet energy of cis-axo-1-bicyclo 2.2.1 heptane utilizing kinetic spectroscopy. The large triplet sensitized (PHI)(,c(--->)t) combined with the lability of the compound thwarted this investigation.

碩士
朝陽科技大學
應用化學系碩士班
90
Abstract Thromboxane A2 is involved in many physiological functions. It is also the cause of many pathological conditions. For example, the increase in thromboxane A2 causes vascular contraction to produce atherosclerosis, thrombosis and asthma. The abnormal secretion of thromboxane A2 and platelet receptor activation may be one of the causes of thrombosis and atherosclerosis. Thromboxane antagonist may be a good approach to these diseases. According to past experience, potent thromboxane antagonist may contain the following pharmacophores, that is, a sulfonamide, an interphenylene ring and a carboxylic acid. The relative position of these three groups decided the potency of these antagonists. Synthesis of all these thromboxane antagonists, starting from exo- 7-oxabicyclo[2.2.1]hept-5-ene-2,3-dicarboxylic anhydride 12, were achieved in 20 steps, leading to enantiopure compounds.

碩士
國立成功大學
藥理學研究所
86
Thromboxane A2 is involved in thrombi formation. It is related to many cardiovascular diseases. Activation of the platelet thromboxane receptor leads to platelet aggregation and secretion of more thromboxane A2. Increase in thromboxane A2 causes vascular contraction. Abnormal platelet receptor activation may be related to thrombosis and atherosclerosis. On the contrary, activation of endothelial thromboxane receptor leads to an increase in production of prostacyclin that opposes thromboxane action. Therefore, selective inhibition of the platelet type receptor may be beneficial in the prevention of thrombosis and atherosclerosis. The objective of our study is to design and synthesize potent thromboxane antagonists with prolonged biological half-lives. According to our previous data, potent thromboxane antagonists may contain the following pharmacophores: a sulfonamide, an inter-phenylene ring and a carboxylic acid. These three groups may be concerned with the potency and activity of the antagonists on thromboxane receptors. Antagonist (±)IPA (2-[(3-phenyl- sulfonylaminobicyclo[2.2.1]hept-2-yl)methyl]-phenylpropanoic acid) was synthesized with biological activity. Preliminary studies also show IPA has potent inhibitory action on platelet aggregation.

碩士
國立中正大學
化學所
97
The syntheses of a series of imide products, such as mono-substituted 36a-c and bis-substituted 37a-c, were successfully achieved by condensations of 34, a multi-functional anhydride, with aryl amines under control of the reagent equivalents. According to our synthetic strategy, the main starting material 34 was prepared by subjecting dicyano compound 33 with basic hydrolysis and acid dehydration. The synthesis of 33 was accomplished by combining building blocks 18 and 30 through enolization and Williamson ether synthesis. Compound 30 was constructed from 4-iodotoluene 27 and 4-methoxy phenol 28 by means of Ullmann reaction and bromination. The conformational isomers of imides 36c and 37c were detected in our characterization. In dynamic NMR studies, the significant interconversions of the conformational isomers were observed, because the increasing temperature technique can overcome the steric hindrance of single bond rotations. The phenomena shown in dynamic NMR spectra provided us reasonable evidence for the isomers we found. So far, the enantiomer of compound 36c was the only isomers characterized with the X-ray diffraction in our research. Furthermore, the enantiomer was also found to self-assemble a dimer which the two methylenes on the bridges were trans to each other by intermolecular π interaction. The phtophsical properties of compounds 36b and 36c were studied by UV-Vis and fluorescence spectrometry. The spectra of 36c showed red-shifted emission, in comparison of the result of 23f.

碩士
國立臺灣師範大學
化學系
105
In this thesis, we focused on development new methodology to synthesize various enantioenriched α-tertiary homoallylic amines by Rhodium(I) catalyst which prepared in situ from Rh(I) catalyst precursor and chiral bicyclic [2.2.1] diene ligand L12j. Rhodium(I) complex catalyzed enantioselective 1,2-addition reactions of potassium allyltrifluo-roborates 31 with cyclic ketimines 30 was found to be highly efficient to afford the desired products with up to 99% yield, 99% ee and 5.5:1.0 dr.

碩士
朝陽科技大學
應用化學系碩士班
93
Ring expansion reactions of bicyclo[2.2.1]carbinol analogues have been widely applied in the preparation for the precursors of natural products and their derivatives. Therefore, they are very important reactions in certain organic synthesis. Herein, we are interested in converting camphene into a formyl bicyclo[2.2.1]carbinol and then into a bicyclo[3.2.1]octanediol . The crucial step of the conversion is the ring expansion reaction that occurs on a formyl bicyclo- [2.2.1]carbinol , which was prepared from camphene. Treatment of formyl bicyclo[2.2.1]carbinol with various alkyl magnesium bromides resulted in ring expansion and alkylation reactions simultaneously to give a bicyclo[3.2.1]- octanediol . The alkyl group of bicyclo[3.2.1]octanediol can be methyl, ethyl, vinyl, allyl or other hydrocarbon groups.

碩士
國立臺灣師範大學
化學系
105
In this thesis, a highly enantioselective rhodium-catalyzed 1,2-addition of aryl boronic acids to aliphatic α-ketoesters and aliphatic ketoamides using Rh-catalyst comprising of a chiral bicyclic [2.2.1] diene ligand L1d is described. This transformation provides chiral tertiary alcohol products with up to 93% yield and 95% ee, product 84 is used for the concise synthesis of the VLA-4 antagonists intermediate.

碩士
國立中山大學
化學系研究所
103
Poly(4-(bicycle[2.2.1]hept-1-en-4-yl)-anthraquinone), PBHEAQ, has been polymerized by ring opening metathesis polymerization, and the electrochemical properties of the polymer are studied. The 4-(bicycle[2.2.1]hept-1-en-4-yl)- anthraquinone (BHEAQ) monomer is synthesized by Heck reaction. Various carbon materials were mixed with the PBHEAQ polymer to fabricate PBHEAQ/carbon composite electrodes using slurry coating. The carbon materials are graphene, Super P, and carbon nanotubes. The electrochemical properties of the Li|PBHEAQ cell are investigated by cyclic voltammetry (CV), charge-discharge measurements, and cycle-life tests. The CV results show a redox couple at 2.0-2.5 V vs. Li/Li+. The charge-discharge result show that the energy capacity of the PBHEAQ is 110 mAh/g. Furthermore, the cycle-life results show that the cells having promising cyclability.

碩士
中原大學
化學研究所
100
This thesis is concerned with asymmetric nitroso-Diels-Alder (ANDA) reactions of masked-o-benzoquinones (MOBs) with nitroso dienophiles deriver from (+)-camphorsulfonic acid. The studied reactions gave 75%-89% yield and 83%-99% disastereoselsetivities and the relationship between specific rotation and absolute configuration of the ANDA products were determined by HPLC and X-ray crystallography.

碩士
國立清華大學
化學系
94
The asymmetric addition of alkynylizinc to benzaldehyde were catalized by the chiral β-amino alcohol 3 derived from ketopinic acid in few stepts. When the addition of alkynylizinc to benzaldehyde was conducted at -20oC in the presence of 10 mol% catalyst, the alkynyl alcohol was obtained in 83% yield and 45% e.e.