No description available.

本文描述了碳環核苷的發展過程，同時也描述了將不同環融合在五元碳環上的方法來對碳環核苷的構象進行鎖定。 / 以D-核糖為起始原料，經過12 步反應並以分子內的Diels-Alder 反應 (IMDA)為關鍵步驟合成出了關鍵的中間體192，它的總產率為27%。通過對中間體192中的環己烯的結構進行修飾，經過3-4 步反應成功合成出了7 個具有雙環[4.3.0]壬烷結構的碳環核苷（185-191），它們的構型也通過其X 光單晶結構圖來進行確定。[附圖] / 以一價銅催化端炔和疊氮化物的Huisgen 環加成反應為關鍵步驟，成功地合成出了12 個具有雙環[4.3.0]壬烷結構的碳環三唑核苷。[附圖] / 同時，我們也合成12 個具有雙環[4.3.0]壬烷結構的碳環三唑核苷羧酸。[附圖] / 另外，我們也合成出了两個在三唑環上含有羧酸的碳環三唑核苷（298 和 299）。[附圖] / 最後，我們還合成出了16 個含有大基團叔丁基羧酸酯的碳環三唑核苷(260-263, 273-276, 286-289 和294-297)。[附圖] / In this thesis, a review regarding the development of carbobicyclic nucleosides and conformationally locked carbobicyclic nucleosides by fusing different rings onto the five-member ring was presented. / The key intermediate 192 was synthesized from D-ribose in 12 steps with 27% overall yield, using an Intramolecular Diels-Alder reaction (IMDA) as the key step. By modification of the cyclohexene ring, seven carbobicyclic adenosine analogues 185-191 with a bicyclo[4.3.0]nonane framework were prepared successfully from intermediate 192 in 3 to 4 steps and their conformations were examined by X-ray crystallography [with diagram]. / Twelve carbobicyclic ribavirin analogues 232-239 and 250-253 with a bicyclo[4.3.0]nonane framework were synthesized successfully by using a copper catalyzed azide-alkyne cycloaddition (Huigsen reaction) as the key step [with diagram]. / Another twelve ribavirin analogues bearing a carboxylate group (264-267, 277-280 and 290-293) with a bicyclo[4.3.0]nonane framework were also obtained [with diagram]. / Furthermore, two more ribavirin analogues bearing a carboxylic acid in triazole (298 and 299) with a bicyclo[4.3.0]nonane framework were obtained. [with diagram] / Finally, twelve ribavirin analogues bearing a tert-butyl carboxylate ester (260-263, 273-276, 286-289 and 290-293) with a bicyclo[4.3.0]nonane framework were also obtained [with diagram]. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Li, Fanglin. / Thesis (Ph.D.) Chinese University of Hong Kong, 2015. / Includes bibliographical references (leaves 175-187). / Abstracts also in Chinese.

Thesis (Ph. D.)--University of Alabama at Birmingham, 2007. / Title from first page of PDF file (viewed Nov. 17, 2008). Includes bibliographical references.

A facile method for the synthesis of highly enriched ¹⁸O labeled pyrimidine ribonucleosides is described. The ribonucleoside may be labelled specifically in the base, the sugar, or both moieties with one or two oxygen-18 atoms. The isotopic purity of the products as well as the location of the oxygen-18 labels have been unambiguously determined by mass spectrometry. Stable isotope labeled analogs have been employed to determine the composition of several clinically significant nucleoside dialdehydes by mass spectrometry. Formation of the trimethylsilyl derivatives permits the gas chromatographic separation of the major components present in the equilibrium mixture. In addition to the expected hemiacetals and hydrates, a substantial amount of the dialdehydes exist in polymeric form. Fast atom bombardment mass spectrometry enabled observation of dimeric and trimeric species from the polymeric material present in the mixture.

As a first generation of compounds, the nucleosides adenosine 8, cytidine 11, guanosine 9, inosine 116 and uridine 12, as well as the sugar ᴅ-(-)-ribose 100, were transformed into the corresponding 5’-O-(tert-butyldiphenylsilyl)- and 5’-O-(4,4’-dimethoxytrityl)-derivatives. These were subsequently protected as acetyl, benzoyl and allyl derivatives at various positions on the molecules, to give a range of twenty five unique compounds for biological testing. The nucleoside and corresponding ᴅ-(-)-ribose derivatives were evaluated for their antibacterial activity against two Gram-positive (Staphylococcus aureus ATCC 25923 and Bacillus cereus DL5) and two Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853 and Escherichia coli ATCC 25922), for their anti-HIV activity against strain HLTVIIIB as well as for their anticancer properties, by evaluating inhibition of cell proliferation in two adherent (HT-29 and Caco-2) and three suspension (HL-60, Jurkat and K-562) cell lines. From these screens, and based on the 2,3,5-triphenyltetrazolium chloride (TTC) assay, it was found that 5’-O-(tert-butyldiphenylsilyl)uridine 107, 5’-O-(tert-butyldiphenylsilyl)-1'-O-methoxy-ᴅ-(-)-ribose 102 and tert-butyldiphenylsilyl alcohol 145 exhibited antimicrobial activity towards only the Gram-positive bacteria when compared to the ciprofloxacin 153 control. None of the compounds tested showed any antiviral activity when assayed against HIV; however, all compounds indicated some form of toxicity to the uninfected cells. Subsequent cell proliferation studies indicated pronounced activity against both the adherent and suspension cancer cell lines for 5’-O-(tert-butyldiphenylsilyl)uridine 107, 5’-O-(tert-butyldiphenylsilyl)cytidine 134, tert-butyldiphenylsilyl alcohol 145, 5’-O-(4,4’-dimethoxytrityl)uridine 126 and 4,4’-dimethoxytrityl alcohol 147. Our initial screen indicated that ᴅ-(-)-ribose derivatives do not show any significant general biological activity; whereas (tert-butyldiphenylsilyl)-protected nucleoside derivatives and the corresponding tert-butyldiphenylsilyl alcohol control are intrinsically more bio-active. From the data reported for the anti-bacterial and the cell proliferation studies, we concluded that the nucleoside showing the most promising results was uridine 12 and our mini structure- activity study on the uridine derivatives found that the best position for performing modifications to the nucleoside was at the 5'-OH position on the sugar ring. As such, this would become the initial focus for the synthesis of the second generation compounds. The second generation compounds included a series of ten uridine 12 and five 5-methyluridine 233 derivatives which were protected on the primary alcohol with a range of different silicon-containing protecting groups. At the same time, we used a general procedure to synthesize a series of fourteen silanols for use as control compounds. The uridine 12, 5-methyluridine 233 and corresponding silanol derivatives were screened for their antibacterial activity against the same two Gram-positive and two Gram-negative bacteria as above, as well as for their anticancer properties, by evaluating inhibition of cell proliferation in a series of six adherent cell lines (five human: Hs683, MCF-7, PC-3, SKMEL-28, U373, and one murine: B16F10) cell lines. The data obtained for our TTC assay showed that converting the base in 1-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,5,-2,4]trioxadisilocin-8-yl]-pyrimidine-2,4(1H,-3H)dione 234 to the 5-methyl derivative 254 caused a corresponding loss in antibacterial activity for the compound, whereas oxidising the secondary alcohol on the 2'-position of the sugar ring to give compound 239 caused a corresponding increase in antibacterial activity. As such, we concluded that 1-[(6aR,8R,9aR)-2,2,4,4-tetraisopropyl-9-oxotetrahydro-6H-furo[3,2-f][1,3,5,-2,4]trioxadisilo-cin-8-yl]pyrimidine-2,4(1H,3H)dione 239 was the compound with the best antibacterial activity out all of the first and second generations of nucleoside derivatives assayed. The results obtained in the TTC assay, were supported by our scanning electron (SEM) and confocal scanning electron (CSLM) microscopy studies. Interestingly, the CSLM study suggests that the synthetic compound 239 is bacteriocidal and is inactivating cells, not simply inhibiting their growth. From the inhibition of cell proliferation assay performed on the fifty combined first and second generation derivatives and their corresponding controls, we found that the six most active compounds (5'-O-(tert-butyldiphenylsilyl)adenosine 142, 5'-O-(tert-butyldiphenyl-silyl)cytidine 134, 5'-O-(tert-butyldiphenylsilyl)uridine 107, 2',3'-O-diacetyl-5'-O-(tert-butyl-diphenylsilyl)uridine 123, 2',3'-O-diacetyl-5'-O-(4,4'-dimethoxytrityl)uridine 127 and 3-benzoyl-1-[(6aR,8R,9R,9aS)-9-hydroxy-2,2,4,4-tetraisopropyltetrahydro-6H-furo[3,2-f][1,3,-5,2,4]trioxa-disilocin-8-yl]pyrimidine-2,4(1H,3H)-dione 235) had mean IC50 values of approximately 24-28 μM.

Thesis (Ph. D.)--West Virginia University, 2004. / Title from document title page. Document formatted into pages; contains xi, 157 p. : ill. (some col.). Includes abstract. Includes bibliographical references.

No description available.

Syntheses of two series of 2'-sugar-modified pyrimido[4,5-b]indole nucleosides were developed. The synthetic strategy was based on functional group transformations of the 2'-hydroxy group of the 3',5'-protected ribonucleoside. The key intermediate was prepared via stereoselective nucleobase anion glycosylation of the known 4,6-dichloropyrimido[4,5-b]indole nucleobase with 2,3-O-isopropylidene- 5-O-TBS-protected halogenose, subsequent deprotection under acidic conditions and protection of 3'- and 5'-hydroxy groups with Markiewicz reagent. Pyrimidoindole arabinonucleoside was then synthesized using a sequence of oxidation-reduction reactions of the 2'-hydroxy stereocenter. The synthesis of pyrimidoindole 2'-deoxy- 2'-fluororibonucleoside was achieved by stereoselective SN2 fluorination of the THP-protected arabinoside followed by acidic deprotection. For the biological activity testing, two series of 4-substituted arabinonucleosides and 2'-deoxy- 2'-fluororibonucleosides were synthesized employing nucleophilic substitution or Pd-catalyzed cross-coupling reactions.

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2009 / N3-substituted pyrimidine nucleoside derivatives containing either an iodovinyl moiety or an allyl group, i.e. [121]-N3-(3-iodoprop-2-en- l -yl)thymidine, (1~-711 and e21]-N3-(prop-2-enl- yl)-5-iodo-Z'-deoxyuridine, (1~_10, were synthesised and preliminarily evaluated by determining their uptake into CHO-Kl cells. Compound e~-711 was designed to be a delivery vector of 121: into the DNA of the cells, while (1~_10 was designed to serve as a control. Compound (1231]-711 was also intended to have a higher metabolic radiochemical stability than 5-iodo-Z'-deoxyuridine ([123I]_IUdR) for the therapeutic use in cancer. The synthesis of the N3-substituted intermediate precursors 411, 5 and 9 was achieved by Nalkylation of suitably' protected thymidine and 5-iodo-Z'-deoxywidine analogues, respectively. The intmediate precursors for radiolabelling, 411 and 11, were obtained by incorporating a trialkylstannyl group at the respective labelling positions prior to radioidination. (1~1-711 was recovered from (1~_6G after acid-hydrolysis of the protecting groups and 10 was obtained from direct oxidative iodination of11. The radiochemical yields ranged from 73% to 91% at the end ofthe synthesis and radiochemical purities were in excess of99"10 after HPLC purification. The cell-uptakes ofthe radiotracers were carried out and assessed by a direct comparison with the gold standard e23I]-IUdR, which is known to bephosphorylated and incorporated into the DNA of cells during the cells S-phase. The cell-uptake results of (1~_711 and (1~-10 were roughly 4% and 3% relative to [123I]-IUdR, respectively. The poor cell-uptake of (1~_10 suggested thatthe uptake into the cells is not influenced by the position of the iodine atom in the molecule, but most probably by the availability of the N3-position in its non-substituted form. As a result of its poor incorporation into cells, it was concluded that the synthesised radiotracer (1231]_711 would be a poor candidate for use in the eradication ofmalignant cells.

by Maggie M. Shi. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1987. / Bibliography: leaves [147]-[173].