Dissertations / Theses on the topic '4-methoxyphenyl'

碩士
中國醫藥大學
藥物化學研究所碩士班
99
Inflammation is the protective response of the injury or microbialinvasion. Overexpression of the inflammatory response and continuous inflammation is closely related to many diseases.Cytokines, adhesion molecules,growth factors and inflammatory factors,and so a large number of enzymes expressed in many inflammatory reactions and the formation of inflammation-related diseases.Inflammatory hormone agonist is a role of inflammatory drug targets for inflammation and symptoms in addition to steroid drugs alsoNSAIDs. Shown in the literature of compounds with naphthyridinones moieties have a variety of pharmacological activities, including anti- inflammatory,and antimicrotubule polymerization. On the other hand amino-quinazolinone in cancer research have been found to inhibit Heat shock protein 90(HSP 90), Lck kinase and other effects, such derivatives have shown potential anticancer activity. To find the path through inhibition of Lck kinase, we also find the relevant aminopyrimidine and its derivativeshave the effect of blocking the MAPK pathway and also has antiinflammatory potential. We try to use the characteristics of these three compounds,synthesis of phenyldihydroquinazolinone the main frame of the compounds.For cell linessuch as A549,PC3,AGS,TW01, compounds can inhibit the activity of cell line proliferation.

碩士
中國醫藥大學
藥物化學研究所碩士班
99
6-(Methoxyphenyl)tetrahydroindazol-4-one derivatives were synthesized and evaluated for antiproliferative activity. Structure-activity relationship was elucidated with various substitutions on the N-1 aryl moiety of tetrahydroindazol-4-one. A novel N-2 aryl-substituted skeleton was established by microwave synthesis. The bioevaluative result was shown that the N-1 substituted tetrahysroindazol-4-one possessed more potential activity against human lung cancer cell (H226), leukemia (Jurkat cell), and nasopharyngeal carcinoma cell (NPC-TW01) than those of corresponding N-2 derivatives. The introduction of oxime moiety at 4-position of tetrahydroindazoles led to a loss of the cytotoxic activity.

碩士
國立中山大學
化學系研究所
93
Flash vacuum pyrolysis (FVP) of 2-azidocycloheptanone gave two products: 3,4,5,6-tetrahydro-1H-azocin-2-one and 1-hydroxy-2-oxo-4- azabicyclo[5.3.0]dec-4-ene-3-spiro-2’-cycloheptanone. Flash vacuum pyrolysis of 2-[2-(4-methoxyphenyl)vinyl]benzofuran gave two products: 4-(2-benzofuran-2-ylvinyl)phenol and 1H-6-oxacyclopenta[c]fluorine.

碩士
中國醫藥大學
藥物化學研究所碩士班
102
Cancer is the leading cause of death in worldwide, and the process of metastasis formation leads to the majority of deaths associated with cancer. Alpha-enolase (ENO-1) has a significant role in cancer metastasis, and ENO-1 linked with glycolysis and energy metabolism in both normal and cancer cells. Therefore, we hoped that inhibited ENO-1 expression could decrease cell migration and invasion. A series of 2-aminobenzofuran derivatives has been successfully synthesized previously and subject to bioevaluation for ENO-1 activity in vitro. That result was shown that the compound BL-082 could inhibit 75% activity of ENO-1 at the value of 10 μM and had cytotoxicity for high metastatic lung adenocarcinoma cells (CL1-5). The thesis was following the previous result to deeply investigate the structure-activity relationship of 2-aminobenzofuran at the substitution of NH2 moiety for ENO-1 activity. The results were shown that the substitution of withdrawing group or donating group on 2-aminobenzofuran could attenuate the ENO-1 inhibitive activity. The compound 11p possessed 2-furonyl substitution on 2-amino moiety was illustrated the good inhibitive activity for ENO-1.

碩士
中國醫藥大學
藥物化學研究所碩士班
94
In our previous studies of 2-phenyl-1,8-naphthyridine-4-one (2-PN) derivatives, compounds with a methyl group at the 5- or 6- position, were potent inhibitors of tubulin polymerization and showed remarkable cytoxicity in vitro against leukemia (HL-60), prostate cancer (PC-3), ovarian cancer (OVCAR-3), CNS cancer (SF-295) and melanoma (SF-MEL-5). 2-phenyl-1,8-naphthyridine-4-ones were synthesized according to following steps: condensation of substituted 2-aminopyridines (4,5) with substituted ethyl benzoylacetates (3) in the presence of polyphosphoric acid formed the corresponding pyridopyrimidinones (6,7). These kinetically favored products were then thermally converted at 350℃ in liquid paraffin to 2-PN (8,9). However, the low water-solubility of 2-PN limits its efficacy in vivo. In order to improve bioavailability by increasing solubility, we introduced hydrophilic group into the 4-position of 2-PN to form 5-methyl-2-(3-methoxyphenyl)-4-O-(β-D-glucopyranosyl)-1,8-naphthyridine (12) and substituted 2-phenyl-1,8-naphthyridin-4-oxyalkylcarboxylic acid (17-24) as target compounds. Further pharmacokinetic investigation is underway to determine if hydrophilic substitution of the 4-position of 2-PNs will result in compounds with increased bioavailability.

碩士
國立中山大學
化學系研究所
94
Flash vacuum pyrolysis of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by dehydrogenation will give 2-(2-naphthalen-2-yl)furan analogues, on the other hand, FVP of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by [1,5]-H shift will give 3-(2-furyl)-1,2-dihydronaphthalene analogues. FVP of 2-[2-(4-methoxyphenyl)vinyl]benzo[b]thiophene gave three products: trans-4-(2-benzo[b]thiophen-2-ylvinyl)phenol, benzo[b]naphtha[1,2-d]thiophen-2-ol and 1H-6-thiacyclopenta[c]fluorene.

碩士
國立彰化師範大學
化學系
101
(7''R)-8-[1-(4'-Hydroxy-3'-methoxyphenyl)prop-2-en-1-yl]galangin, a new flavonoid isolated from Mexican propolis in 2010, displays preferential cytotoxicity against PANC-1 cells of human pancreatic cell line. First, the preparation of 8-bromo galangin was begun from the commercially available phloroglucinol. The phloroglucinol was converted by methylation and acetylation reactions to give dimethoxyphenyl acetate in two steps overall 49% yield. The dimethoxyphenyl acetate was transformed by Fries rearrangement in presence of AlCl3 to give acetophenone in 58% yield. Continually, to couple acetophenone and benzaldehyde with aldol condensation was performed to afford chalcone. The chalcone was converted to galangin by Algar-Flynn-Oyamada reactiont in existence of 20% NaOH and H2O2 in MeOH. However, it’s failed to get the desired galangin. Alternatively, the chrysin was employed by hydroxylation and bromination reactions to obtain the 8-bromo galangin in four steps overall 32% yield. On the other hand, the propiophenone was provided by Friedel-Crafts reaction of 2-methoxyphenol and propionic acid under BF3．OEt2 in 69% yield. In addition, propiophenone was converted to bromopropene under the presence of PBr3/ DMF in 70% yield, and then followed by SeO2 oxidation to give alcohol compound. The corresponding α-vinylstannane was successfully prepared in existence of t-BuLi/SnBu3Cl in moderate 59% yield. Finally, 8-bromo galangin and α-vinylstannane were transformed by Stille coupling reaction to afford the precursor (7''R)-8-[1-(4'-Hydroxy-3'-methoxyphenyl)prop-2-en-1-yl]galangin in 36% yield.

碩士
中國醫藥大學
藥物化學研究所碩士班
98
Abstract In the previous study, 2-(3-methoxyphenyl)-6-methyl-1,8-naphthyridin-4-one（LYF-5）was synthesized and found to possess strong cytotoxicity. Because of its low hydrophilicity, an attempt was made to synthesize of its 4-phosphate. Whereas the poor stability proinhibited it from further development . In this study, two kinds of target compounds, including hydroxyl derivatives（IIa-IIc、IIIa、IVa、IVb） and 8-N-oxide（Va）were designed. Condensation of 2-amiopyridine with benzoyl acetates in PPA formed the corresponding pyrido-pyrimidines（5a-5g）. Thermal rearrangement in mineral oil yielded the corresponding naphthyridinones（6a-6g）. Finally, these naphthyridin-ones（6a-6e）were demethylated separately with HBr to give the corresponding hydroxyl derivatives（7a-7f）. On the other hand, LYF-5 was oxidated by reacting with m-CPBA to 2-(3-methoxyphenyl)-6-methyl-1,8-naphthyridin-4-one 8-N-oxide（Va）. The synthesized hydroxyl drivatives（IIa-IIc、7d、IIIa、IVa、IVb）and 8-N-oxide compound（Va）were evaluated for their cytotoxicity against three cancer cell lines and human normal cell line. Among these tested compounds, 2-(3-hydroxyphenyl) -6-methyl-1,8-naphthyridin-4-one（IIb）exhibited promising cell growth inhibitory activity against three cancer cell lines with low cytotoxicity against human normal cell line. Compound that is IIb will be used as a parent molecule for preparing itswater solube phosphate that could be used for animal study.

Synthese siliciumhaltiger Wirkstoffe und Synthese-Bausteine des 4-Silapiperidin-Typs: Im Rahmen der systematischen Untersuchungen unseres Arbeitskreises zur C/Si-Bioisosterie wurde für bereits bekannte σ-Rezeptor-Antagonisten eine neue verbesserte Syntheseroute entwickelt, wobei die Endprodukte jeweils in einer sechsstufigen Synthese dargestellt und als entsprechende Hydrochloride isoliert wurden. Ein weiteres Teilprojekt der vorliegenden Arbeit betraf die Entwicklung einer Syntheseroute zur Darstellung von Sila-L-741,626, dem Sila-Analogon des selektiven D2-Dopamin-Rezeptorantagonisten L-741,626. In einem weiteren Teilprojekt der vorliegenden Arbeit wurde ein neuer, säurefreier Weg zu 4 Silapiperidin-Bausteinen mit NH-Funktion entwickelt, der eine Staudinger-Reaktion als ringschließenden Syntheseschritt beinhaltet. Am Beispiel einer Modellverbindung, die in zwei alternativen jeweils fünfstufigen Synthesen ausgehend von Dichlordiphenylsilan dargestellt und als Hydrochlorid isoliert wurde, konnte die neue Syntheseroute erfolgreich ausgearbeitet werden. Die anhand der Modellverbindung erfolgreich getestete Syntheseroute konnte im Folgenden auf ein Zielmolekül angewendet werden, das anstatt einer inerten Phenyl-Gruppe die säurelabilere 4-Methoxyphenyl- (MOP-) Gruppe trägt. Synthese siliciumhaltiger Wirkstoffe und Synthese-Bausteine des 4-Silacyclohexan-1-on- und (4-Silacyclohexan-1-yl)amin-Typs: Im Zusammenhang mit unseren systematischen Untersuchungen zur C/Si-Bioisosterie wurde Sila-pramiverin dargestellt. Dies gelang in einer vierstufigen Synthese, ausgehend von Dichlordiphenylsilan. Im Zuge dieser Synthese fand Brown’s DCME-Prozess Anwendung, um in einer Eintopf-Reaktion das entsprechende 4-Silacyclohexan-1-on und daraus durch anschließende reduktive Aminierung mit Isopropylamin Sila-pramiverin erstmals darzustellen. Analog zur Synthese von Sila-pramiverin konnten ebenfalls Synthese-Bausteine des 4 Silacyclohexan-1-on-Typs sowie des (4-Silacyclohexan-1-yl)amin-Typs unter Verwendung der 4 Methoxyphenyl- (MOP ), 2,6-Dimethoxyphenyl- (DMOP-) bzw. 2,4,6-Trimethoxyphenyl- (TMOP-) Schutzgruppe dargestellt werden. In einer Machbarkeitsstudie wurde zudem unter selektiver Abspaltung der 4 Methoxyphenyl- (MOP ), 2,6-Dimethoxyphenyl- (DMOP-) bzw. 2,4,6-Trimethoxyphenyl- (TMOP-) Schutzgruppe der phenylierten 4 Silacyclohexan-1-one mittels Chlorwasserstoff das entsprechende Chlorsilan dargestellt. Synthese siliciumhaltiger Synthese-Bausteine des 4-Silatetrahydropyran-Typs: Eine fast gänzlich unerforschte Klasse siliciumhaltiger Heterocyclen stellen 4 Silatetrahydropyrane dar. Im Rahmen der vorliegenden Arbeit konnte zunächst anhand einer Modellstudie das 4,4-Diphenyl-4-silatetrahydropyran dargestellt werden. Die für die Modellverbindung ausgearbeitete Syntheseroute konnte schließlich auf die Synthese der 4 Methoxyphenyl- (MOP-) und 2,6-Dimethoxyphenyl- (DMOP-) substituierten 4 Silatetra¬hydropyrane übertragen werden. Diese konnten jeweils in einer vierstufigen Synthese dargestellt werden. Lediglich die Synthese der 2,4,6-Trimethoxyphenyl- (TMOP-) substituierten 4 Silatetra¬hyropyrane gelang aufgrund der Instabilität der mesylierten Zwischenstufen nicht
Synthesis of silicon containing drugs and building blocks of the 4-silapiperidine type: In context with the systematic studies of our research group on C/Si bioisosterism, a novel and improved synthetic route for already reported σ receptor antagonists were established in six-step syntheses, and the final products were isolated as hydrochlorides. Another goal of this work concerned the development of a synthetic route for sila L 741,626, a silicon analogue of the selective D2 dopamin receptor antagonist L 741,626. In another project of this work, a novel acid-free method for the synthesis of 4-silapiperidine building blocks containing a NH function has been developed, using the Staudinger reaction as the key step. As a proof of principle, a model compound, isolated as hydrochloride, could be prepared in two alternative five-step syntheses, starting from dichlorodiphenylsilane. The novel synthetic route for the preparation of the model compound could then be sucessfully applied to the synthesis of a novel target molecule containing the more acid-labile 4 methoxyphenyl (MOP) group instead of the relatively inert phenyl group. Synthesis of silicon containing drugs and building blocks of the 4-silacyclohexan-1-one and the (4-silacyclohexan-1-yl)amine type: In context with our systematic studies on C/Si bioisosterism, sila-pramiverin was synthesized in a four-step synthesis, starting from dichloro¬diphenylsilane. In the course of the synthesis of the 4 silacyclohexan-1-one intermediate, a one-pot synthesis by using Brown’s DCME process was applied. Subsequent reductive amination with isopropylamine led to sila-pramiverin. Analogously to the synthesis of sila-pramiverin, building blocks of the 4 silacyclo¬hexan-1-one type and the (4-silacyclohexan-1-yl)amine type were synthesized by using the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), or 2,4,6-trimethoxyphenyl (TMOP) protecting groups. As a proof of principle, the phenyl-substituted 4 silacyclo¬hexan-1-ones could then be transformed into the corresponding chlorosilane by selective cleavage of the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), or 2,4,6-trimethoxyphenyl (TMOP) protecting group by using hydrogen chloride. Synthesis of silicon containing building blocks of the 4-silatetrahydropyrane type: 4-Silatetrahydropyranes represent a nearly unexplored class of silicon containing heterocycles. Within the scope of this work, the model compound 4,4-diphenyl-4-silatetrahydropyrane could be synthesized in a three-step synthesis, starting from dichlorodiphenylsilane. This synthetic route to the model compound could then also be applied successfully to the 4-methoxyphenyl (MOP) and 2,6-dimethoxyphenyl (DMOP) substituted 4-silatetrahydropyranes. However, the syntheses of the 2,4,6-trimethoxyphenyl (TMOP) substituted 4 silatetrahydropyranes remained unsuccessful due to the instability of their mesylated precursors

碩士
中國文化大學
應用化學研究所
94
The investigation of this research involves the synthesis and intermolecular [m+n] cycloadditions of the unsymmetrically electron-rich 6-(1,1-Diethylmethyl)fulvene and 6-(4-methoxyphenyl)fulvene with 8,8-dicyaoheptafulvene; designed to establish the experimental analyses of the reactivity, diastereoselectivity, periselectivity, and regioselectivity of these cycloadditions. The experiment uses 1H-NMR, COSY, NOESY, E.I.M.S., H.E.I.M.S.À is judged . The result shows, under the gentle response condition of the room temperature, 8,8-Dicyanoheptafulvene to be 6 - (1', 1' - Diethylmethyl)fulvene react , have [8+2 ] with [4+2 ] react. In [8+2] is it can demonstrate the a hundred per cent three-dimensional alternative and reverse (Anti) to react, and with to ( Syn ) in [4+2] is it can demonstrate the a hundred per cent three-dimensional alternative to react. [8+2] : [4+2] in a ratio of about 1:1. The cycloaddition reaction of 8,8-Dicyanoheptafulvene with 6-(4-Methoxyphenyl)fulvene at room temperature gave the [8+2] : [6+4] in a ratio of about 1:4.

碩士
國立臺北科技大學
化學工程研究所
103
An aromatic secondary amine N,N’-bis(4-methoxyphenyl)-1,4- phenylenediamine (1) was synthesized by condensation of p-anisidine with hydroquinone. Subsequent condensation of compound 1 with p-fluoronitrobenzene resulted in the dinitro compound N,N’-bis(4-nitrophenyl)-N,N’-bis(4-methoxy- phenyl)-1,4-phenylenediamine (2), which was then reduced to the target diamine monomer, N,N’-bis(4-aminophenyl)-N,N’-bis(4-methoxyphenyl)-1,4-phenylene- diamine (3). A new dicarboxylic acid monomer bearing two built-in imide rings, namely N,N’-bis(trimellitimidophenyl)-N,N’-bis(4-methoxyphenyl)-1,4-phenylene- diamine (4), was synthesized from condensation of diamine 3 with two equivalent amount of trimellitic anhydride. New poly(amide-imide)s (PAIs) containing N,N’-di(4-methoxyphenyl)-N,N’-diphenyl-p-phenylenediamine [TPPA(OMe)2] units were prepared by the phosphorylation polyamidation reaction from diamine 3 with four imide ring-preformed dicarboxylic acids or from diimide-diacid 4 with 4,4’-oxydianiline and diamine 3, respectively, via the phosphorylation amidation reaction. All the PAIs were readily soluble in many organic solvents and could be solution-cast into tough and flexible polymer films. These PAIs showed glass-transition temperatures (Tgs) in the range of 206-292 °C, and most of them did not show significant weight-loss before 450 oC. Cyclic voltammograms of the PAI films cast onto the indium-tin oxide (ITO)-coated glass substrate revealed reversible electrochemical oxidation processes accompanied with strong color changes from the pale yellow neutral state to yellowish green and deep blue oxidized forms at applied potentials ranging from 0 to 1.0 V. Incorporating the TPPA(OMe)2 unit on the amide side of PAIs led to lower oxidation potentials and higher redox reversibility and, thus, better electrochromic performance such as higher coloration efficiency, faster switching speed, and higher electrochromic stability.

碩士
國立中山大學
化學系研究所
100
一、Pyrolysis of 2-azido-1-(4-methoxyphenyl)ethanone (69) and 2-(2-azidoethyl)furan (85) gave nitrene intermediate to study. There is 2-(4-methoxybenzoyl)-4-(4- methoxyphenyl)imidazole (81) 、2-(4-methoxybenzoyl)-5-(4-methoxyphenyl) imidazole] (81’)、2,3-di(4-methoxybenzoyl)-5-(4-methoxyphenyl) pyrazine] (82) and 3,5-di(2-furyl) pyridine (92) for pyrolysis products. 二、Pyrolysis of3-methyl-2-cyclohexen[b] furylmethyl benzoate) (50) gave carbene intermediate to study. There is 2,3-dimethylene cyclohexen[b]furan (59) for pyrolysis products.

博士
中國醫藥大學
藥物化學研究所
92
We previously reported that HMJ-38 was the most potent 2-phenyl-4-quinazolinone derivative in inhibiting tubulin polymerization and showed significant cytotoxicity against several human tumor cell lines. In this study, we studied its cytotoxic effect on HL-60 leukemia cells and underlying mechanisms and investigated the anticancer activity of HMJ-38 in syngeneic BALB/c mice bearing murine WEHI-3 leukemia cells. We first investigated the effects of HMJ-38 on viability, cell cycle and induction of apoptosis in leukemia cell lines (HL-60, U937 and K562) and normal human peripheral blood mononuclear cells. After 24 hours of treatment with HMJ-38, concentration- and time-dependent decreases in the viability of HL-60, U937 and K562 cells were observed and the IC50 value were estimated to be 4.48, 5.06 and 8.87 M. The cytotoxic effect of HMJ-38 on PBMC was less significant than that on HL-60 cells after 24 or 48 hours of treatment. Immunocytochemistry staining of -tubulin demonstrated that, which was also observed in colchicine-treated cells, HMJ-38 inhibited the polymerization of microtubules. Cell cycle analysis showed that HMJ-38 induced significant G2/M arrest and apoptosis in HL-60 cells. The HMJ-38 induced-G2/M arrest occurred before the onset of apoptosis. Within 24 hours of treatment, HMJ-38 affected the CDK/cyclin B activity by increasing Chk1, Wee1 and p21, and decreasing Cdc25c protein levels. The HMJ-38-induced apoptosis was further confirmed by morphological assessment and DNA fragmentation assay. Induction of apoptosis in HMJ-38-treated HL-60 cells was accompanied by an apparent increase of cytosolic cytochrome c, down-regulation of Bcl-2 and survivin, up-regulation of Bax and Bak, and cleavage of Bid, pro-caspase-9, -3, and poly(ADP)ribosylpolymerase (PARP). Results of the significant reduction of caspase activities and apoptosis by caspase inhibitors indicated that the HMJ-38-induced apoptosis was mainly mediated by activation of caspases-9 and -3. HMJ-38 also activated ERK in HL-60 cells. Pre-incubating cells with ERK inhibitors (U0126 and PD98059) attenuated the HMJ-38 induced ERK activation and apoptosis. Nevertheless, cells remained arrested in G2/M. Before performing animal studies, we confirmed that HMJ-38 concentration-dependently decreased viability of WEHI-3 cells with an IC50 of 5.0 M. HMJ-38-induced G2/M arrest companioned by apoptosis was further confirmed by morphological assessment, cell cycle analysis and DNA fragmentation assay. Intravenous injection of WEHI-3 cells in a high number (1X106) into Balb/c mice successfully induced leukemia in these mice 28 days later. HMJ-38 treatment (i.v. of 2.5 mg/kg/2 days for 14 days) started at 14 days after WEHI-3 cell injection. Taxol at a dose of 5 mg/kg/day was used as the positive control for comparison. In animal study, HMJ-38 enhanced survival rate and prevent the body weight loss in leukemia mice within one month of experiment. The enlargement of spleen and lymph nodes and liver metastasis were significantly reduced in HMJ-38 treated groups. H-E stain of spleen sections revealed that infiltration of immature myeloblastic cells into splenic red pulp was reduced in HMJ-38 treated groups. Flow cytometric analysis of leukocyte subtypes in PBMC showed that CD19+ cell population was significantly increased to normal range in HMJ-38- or taxol-treated leukemia mice than that in untreated leukemia mice. In contrast, the CD14+ and Mac-3+ cell populations in the HMJ-38 treated leukemia Balb/c mice were significantly reduced to normal range than those in untreated group. These results suggest that HMJ-38 is a potent anticancer drug. It shows a remarkable action on cell cycle before commitment for apoptosis is reached. In addition, HMJ-38 demonstrates prominent anti-cancer activity in WEHI-3/Balb/c leukemia model.

碩士
中國文化大學
應用化學研究所
93
The investigation of this research involves the synthesis and intermolecular [m+n] cycloadditions of the unsymmetrically electron-rich 6-monosubstituted 6-phenylfulvene (1n) 6-(4-Methoxyphenyl)fulvene, 6-(4-Nitrophenyl)fulvene with 8,8-dicyaoheptafulvene (8a); designed to establish the experimental analyses of the reactivity, diastereoselectivity, periselectivity, and regioselectivity of these cycloadditions. The cycloaddition reaction of 8,8-dicyanoheptafulvene (8a) with 6-phenylfulvene (1n) at room temperature gave the anti-endo-[6+4] cycloadducts 21n/21n’(1:1 ratio) and the anti-endo-[8+2] cycloadduct 17n in a ratio of about 1:1. The present results show that these [8+2] and [6+4] cycloaddition reactions took place with exclusive endo diastereoselectivity and anti regioselectivity. Good periselectivity was also observed. The cycloaddition reaction of 8,8-dicyanoheptafulvene (8a) with 6-(4-Methoxyphenyl)fulvene (2n) at room temperature gave the anti-endo-[6+4] cycloadducts 24n/24n’(1:1 ratio) and the anti-endo-[8+2] cycloadduct 22n/22n’ in a ratio of about 1:1. The present results show that these [8+2] and [6+4] cycloaddition reactions took place with exclusive endo diastereoselectivity and anti regioselectivity. Good periselectivity was also observed.

碩士
中國文化大學
應用化學研究所
94
The investigation of this research involves the synthesis and intermolecular [m+n] cycloadditions of the unsymmetrically electron-rich 6-monosubstituted 6-(4-methoxyphenyl)fulvene with 8,8-dicyaoheptafulvene ; designed to establish the experimental analyses of the reactivity, diastereoselectivity, periselectivity, and regioselectivity of these cycloadditions. The cycloaddition reaction of 8,8-dicyanoheptafulvene with 6-(4-methoxyphenyl)fulvene at room temperature gave the anti-endo-[6+4] cycloadducts 23n/23n’(1:1 ratio) and. The present results show that these [6+4] cycloaddition reactions took place with exclusive endo diastereoselectivity and anti regioselectivity. Good periselectivity was also observed.

ABSTRACT

Phenols are ubiquitous in our surroundings including biological molecules such as L-Dopa metabolites, food components, such as whiskey and liquid smoke, etc. This dissertation describes a new method for detecting phenols, by reaction with Gibbs reagent to form indophenols, followed by mass spectrometric detection. Unlike the standard Gibbs reaction which uses a colorimetric approach, the use of mass spectrometry allows for simultaneous detection of differently substituted phenols. The procedure is demonstrated to work for a large variety of phenols without para‐substitution. With para‐substituted phenols, Gibbs products are still often observed, but the specific product depends on the substituent. For para groups with high electronegativity, such as methoxy or halogens, the reaction proceeds by displacement of the substituent. For groups with lower electronegativity, such as amino or alkyl groups, Gibbs products are observed that retain the substituent, indicating that the reaction occurs at the ortho or meta position. In mixtures of phenols, the relative intensities of the Gibbs products are proportional to the relative concentrations, and concentrations as low as 1 μmol/L can be detected. The method is applied to the qualitative analysis of commercial liquid smoke, and it is found that hickory and mesquite flavors have significantly different phenolic composition.

In the course of this study, we used this technique to quantify major phenol derivatives in commercial products such as liquid smoke (catechol, guaiacol and syringol) and whiskey (o-cresol, guaiacol and syringol) as the phenol derivatives are a significant part of the aroma of foodstuffs and alcoholic beverages. For instance, phenolic compounds are partly responsible for the taste, aroma and the smokiness in Liquid Smokes and Scotch whiskies.

In the analysis of Liquid Smokes, we have carried out an analysis of phenols in commercial liquid smoke by using the reaction with Gibbs reagent followed by analysis using electrospray ionization mass spectrometry (ESI-MS). This analysis technique allows us to avoid any separation and/or solvent extraction steps before MS analysis. With this analysis, we are able to determine and compare the phenolic compositions of hickory, mesquite, pecan and apple wood flavors of liquid smoke.

In the analysis of phenols in whiskey, we describe the detection of the Gibbs products from the phenols in four different commercial Scotch whiskies by using simple ESI-MS. In addition, by addition of an internal standard, 5,6,7,8-tetrahydro-1-napthol (THN), concentrations of the major phenols in the whiskies are readily obtained. With this analysis we are able to determine and compare the composition of phenols in them and their contribution in the taste, smokey, and aroma to the whiskies.

Another important class of phenols are found in biological samples, such as L-Dopa and its metabolites, which are neurotransmitters and play important roles in living systems. In this work, we describe the detection of Gibbs products formed from these neurotransmitters after reaction with Gibbs reagent and analysis by using simple ESI‐MS. This technique would be an alternative method for the detection and simultaneous quantification of these neurotransmitters.

Finally, in the course of this work, we found that the positive Gibbs tests are obtained for a wide range of para-substituted phenols, and that, in most cases, substitution occurs by displacement of the para-substituent. In addition, there is generally an additional unique second-phenol-addition product, which conveniently can be used from an analytical perspective to distinguish para-substituted phenols from the unsubstituted versions. In addition to using the methodology for phenol analysis, we are examining the mechanism of indophenol formation, particularly with the para-substituted phenols.

The importance of peptides to the scientific world is enormous and, therefore, their structures, properties, and reactivity are exceptionally well-characterized by mass spectrometry and electrospray ionization. In the dipeptide work, we have used mass spectrometry to examine the dissociation of dipeptides of phenylalanine (Phe), containing sulfonated tag as a charge carrier (Phe*), proline (Pro) to investigate their gas phase dissociation. The presence of sulfonated tag (SO₃^-) on the Phe amino acid serves as the charge carrier such that the dipeptide backbone has a canonical structure and is not protonated. Phe-Pro dipeptide and their derivatives were synthesized and analyzed by LCQ-Deca mass spectroscopy to get the fragmentation mechanism. To confirm that fragmentation path, we also synthesized dikitopeparazines and oxazolines from all combinations of the dipeptides. All these analyses were confirmed by isotopic labeling experiments and determination and optimization of structures were carried out using theoretical calculation. We have found that the fragmentation of Phe*Pro and ProPhe* dipeptides form sequence specific b₂ ions. In addition, not only is the ‘mobile proton’ involved in the dissociation process, but also is the ‘backbone hydrogen’ is involved in forming b₂ ions.