(1)合成β(1→4)雙葡萄醣胺醣胜肽 (2)合成全保護的半乳醣胺

The first part of the thesis describes the discovery of glycopeptide and its potential value of imaging probe for tumor angiogenesis. How to synthesize GP is the point of this thesis and this article provides a reaction path way to synthesize diglucosamine and tries to increase the length of the sugar link. We hope to develop a new type drug which can be a selective to tumor cells. The second part of this thesis descrips GD2, GT2, GM1 and Tn agent and provides a deferent way to make the bulding blocks of full protected galatosamine. Using glucosamine as starting material the price of synthesis can be lower.論文的第一部分在說明醣胜肽的發現以及其潛力價值，如何合成醣胜肽為本論文的重點。本篇提供了一種合成醣胜肽的反應路徑，並希望能夠增加醣的數目，以符合醣胜肽分子的特性，並找出對腫瘤細胞有著良好選擇性的醣胜肽產物。並期望能開發出一新型藥物，能作為藥物載體或能作為正電子發射計算機斷層掃描顯影所需的放射性注射藥物。 第二部分主要作為GD2、GT2、GM1和Tn抗原等藥物分子的建構基石，將較為便宜的葡萄糖胺轉換成價格昂貴的半乳糖胺，並為了合成上述生物分子設計了具有保護基的半乳糖胺。目次 摘要.......................................................................................................... ii Abstract..................................................................................................... iii 目次......................................................................................................... iv 表目次...................................................................................................... vii 圖目次..................................................................................................... viii 流程目次................................................................................................ ix 縮寫表....................................................................................................... x 第一部分：................................................................................................ 1 合成β(1→4)雙葡萄醣胺醣胜肽................................................................. 1 Synthesis of glycopeptide of β(1→4) diglucosamine............................. 1 一、 緒論.................................................................................................... 2 (一) 前言................................................................................................ 2 (二) 癌細胞的形成與治療.................................................................... 2 (三) 正電子發射計算機斷層掃描(Positron Emission Tomography, PET) ............................................................................................... 4 (四) 氟代脫氧葡萄糖(Fludeoxyglucose, 18F-FDG)............................. 4 (五) 葡萄糖胺(glucosamine)................................................................. 5 (六) 谷氨酸(glutamic acid) ....................................................................8 (七) 醣胜肽(glycopeptide, GP)的發現與活性.....................................9 (八) 醣苷鍵的立體位向選擇性…...................................................... 15 1. 變旋異構效應(Anomeric Effect) ...................................... 16 (1) 誘導效應(Inductive effect) .......................................... 17 (2) 偶極穩定能(Dipole Stabilization) ............................... 18 (3) 電子斥力(Electronic Repulsion) ............................... 19 2. 溶劑效應(Solvent Effect) ............................................... 19 3. 鄰基效應(Neighboring group Effect) .......................... 20 (九) 雙葡萄糖胺文獻回顧......................................................... 21 二、 結果與討論...................................................................................... 25 (一) 醣胜肽之逆合成分析.................................................................. 25 (二) 葡萄糖胺之醣受體合成.............................................................. 26 (三) 葡萄糖胺之醣予體合成.............................................................. 29 (四) 雙葡萄糖胺合成.......................................................................... 30 三、 結論............................................................................................... 32 第二部分：................................................................................................. 33 合成全保護的半乳醣胺............................................................................ 33 Synthesis of protected galactosamine...................................................... 33 四、 緒論.................................................................................................. 34 (一) 前言.............................................................................................. 34 (二) 藥物中的半乳醣胺...................................................................... 36 (三) Tn抗原介紹................................................................................. 38 (四) 神經節苷脂(Ganglioside)介紹.................................................... 38 (五) 研究目標...................................................................................... 40 (六) 半乳糖胺衍生物文獻回顧.......................................................... 40 1. 由N-乙醯葡萄醣胺合成一系列N-乙醯胺六碳醣衍生物...................................................................................... 40 2. 由N-乙醯葡萄醣胺有效的轉換為N-乙醯半乳醣胺...... 41 3. MECA-79中的半乳醣胺合成....................................... 42 五、 結果與討論.................................................................................. 44 (一)半乳糖胺衍生物的逆合成分析................................................... 44 六、 結論............................................................................................... 46 七、 實驗部分....................................................................................... 47 (一) 一般實驗敘述..................................................................... 47 (二) 實驗步驟與物理數據......................................................... 48 八、 參考文獻(一)................................................................................... 61 九、 參考文獻(二)................................................................................... 63 十、 化合物核磁共振光譜圖............................................................... 64 表目次 表一、68Ga-GP在乳癌小白鼠體內分布情形.............................................12 表二、FDG在乳癌小白鼠體內分布情形..................................................13 圖目次 圖一、腫瘤細胞示意圖...............................................................................3 圖二、PET裝置圖.......................................................................................4 圖三、殼聚糖(chitosan)結構.......................................................................6 圖四、谷氨酸(glutamic acid)結構...............................................................9 圖五、glycopeptide (GP)結構....................................................................10 圖六、以膠體滲透層析法(GPC)分析GP..................................................11 圖七、以99mTc-GP餵食乳癌細胞.............................................................11 圖八、68Ga-GP的PET顯影圖(圖中為乳癌的紐西蘭小白兔) ...............14 圖九、常見之醣苷.....................................................................................16 圖十、 誘導效應示意圖.............................................................................18 圖十一、偶極穩定能示意圖.....................................................................18 圖十二、電子斥力示意圖.........................................................................19 圖十三、膽固醇結構.................................................................................35 圖十四、核苷酸的基本結構.....................................................................36 圖十五、Tn antigen及其衍生物................................................................37 圖十六、ganglioside GM1、GD2、GT2結構..............................................37 圖十七、神經節苷脂(ganglioside)分類表................................................39 圖十八、MECA-79之結構........................................................................43 流程目次 流程一、18F-FDG合成方法..........................................................................5 流程二、EGA的合成....................................................................................7 流程三、以乙醯葡萄糖胺合成3A5AF.........................................................8 流程四、變旋異構效應示意圖...................................................................18 流程五、溶劑效應示意圖...........................................................................20 流程六、鄰基效應.......................................................................................20 流程七、葡萄糖胺醣予體合成...................................................................21 流程八、雙葡萄糖胺合成策略(一) ............................................................22 流程九、雙葡萄糖胺合成策略(二) ............................................................23 流程十、GP之逆合成分析.........................................................................25 流程十一、葡萄糖胺醣受體之合成(一) ....................................................27 流程十二、葡萄糖胺醣受體之合成(二) ....................................................29 流程十三、葡萄糖胺醣予體之合成...........................................................29 流程十四、雙葡萄糖胺長鏈合成...............................................................31 流程十五、N-乙醯半乳醣胺甲脂的製備...................................................41 流程十六、由N-乙醯葡萄醣胺有效的轉換為N-乙醯半乳醣胺..............42 流程十七、MECA-79中Tn抗原片段製備................................................43 流程十八、半乳糖胺衍生物的逆合成分析...............................................44 流程十九、半乳糖胺衍生物合成...............................................................45 流程二十、半乳糖胺衍生物的逆合成分析...............................................4

MLB-PoL: A High Performance Hybrid Converter for Direct 48 V to Point-of-Load Applications

There is an increasing need for more efficient power conversion from 48 Vdc to point-of-load (PoL) applications in datacenters. This work presents a new hybrid converter with Multi-Level Binary (MLB) voltages on the flying capacitors that is well-suited for PoL applications with very high conversion ratios. The proposed MLB-PoL converter can be viewed as an 8-to-1 multi-phase doubler switched-capacitor (SC) converter merged with a two-phase interleaved buck converter. Compared to other two-phase hybrid SC topologies, multi-phase operation can help achieve higher conversion ratio in the SC stage with an equal or fewer number of components, and thus reduce the switch andinductor stress of the following buck stage. In addition, the output inductors in the proposed topology benefit from a frequency multiplication effect similar to that of the flying capacitor multilevel (FCML) converter. This can help further reduce the inductor size without increasing the switching frequency. A 48 V to 2.5-1.0 V converter prototype with 65 A output current was built and tested. At 48 V to 2 V, the prototype achieved 95.1% peak efficiency (94.3% including gate drive loss) and 395 W/in3 power density

Architecture and Control of An Interleaved 6-Level Bidirectional Converter With an Active Energy Buffer for Level-II Electric Vehicle Charging

On-board electric vehicle (EV) chargers convert grid ac voltage to dc voltage to charge a high-voltage battery pack. High efficiency and high power density single-phase ac-dc converters are desirable in such applications to reduce the heat loss, volume and weight of these chargers. Moreover, the capability of bidirectional conversion is preferred for potential vehicle-to-grid applications. This paper presents the system ar-chitecture and embedded digital control implementation of a 7 kW, universal ac (120-240 VAC) to 400 VDC single-phase ac-dc bidirectional converter. The converter features an interleaved 6-level flying capacitor multilevel (FCML) ac-dc stage and a series-stacked buffer for buffering twice-line frequency pulsating power to achieve high efficiency and power density. Test results that demonstrate both ac-dc power factor correction (PFC) and inverter operation at kilowatt levels are provided

Mild and Highly α‐Selective O‐Sialylation Method Based on Pre‐Activation: Access to Gangliosides Hp‐s1, DSG‐A, and Their Analogues

An efficient method for α‐selective sialylation, based on a pre‐activated 5‐N,4‐O‐carbamate thiosialoside donor using p‐TolSCl/AgOTf as reagents, is described. The strategy is further expanded to a range of sugars. A mechanism is proposed and validated using experimental evidence. The utility of the method is demonstrated by the total synthesis of gangliosides Hp‐s1 1, DSG‐A 2 and their analogues, 2 a–2 c. The neuritogenic activity of the final compounds is determined on SH‐SY5Y cells