臺灣博碩士論文加值系統

(I) 計畫一

四級立體中心是在天然物重要的結構，Meyers’ 內醯胺是建構立體中心有效的模板，在以前的研究中，此方法是透過一系列烷基化所建構立體中心，而本篇論文我們主要是透過鈀金屬催化的雙環內酰胺的α-芳基化以提供具有芳基的立體中心，進而經由轉換得到具有芳香基取代之立體中心。在本章節中，我們亦研究了通過氫化物轉移產生的雜環產物之新反應性，在對反應條件進行廣泛篩選後，我們發現使用共鹼系統可以改善反應。此外，檢查單烷基化雙環內酰胺和起始內酰胺皆能得到相應的芳基開環產物。

(II)計畫二

Schulzeines是Fusetani團隊於2004年從海綿中分離出的天然產物，這些生物鹼被發現可抑制alpha-葡萄糖苷酶和病毒神經氨酸酶。值得注意的是，脫硫的schulzeines也可以抑制酶。我們的合成設計的關鍵步驟是形成1,2-哌啶酮核的正式[3 + 3]氮雜環。 經過一系列反應優化後，我們發現正式[3 + 3]氮雜環化的最佳條件是使用丙烯酸作為三碳供體和對二甲苯作為溶劑，從而建立三環骨架。通過包含烯烴還原和alpha-胺化反應的兩步序列，我們完成了schulzeine C的正式全合成。我們還將討論合成脫硫化的schulzeine C和相關合成衍生物的努力。

(I) project 1:
Quaternary carbon stereocenter is an important trait in natural products. Meyers’ lactam is a useful template to construct a quaternary carbon stereocenter. In previous works, quaternary carbon stereocenter was settled by sequential alkylation. Herein, we focused on palladium-catalyzed -arylation of bicyclic lactam to furnish a stereocenter with aryl group. In this chapter, we also describe a new reactivity to generate heterocyclic ring product through hydride shift. After extensive screening of the condition, we found that reaction conversion was improved by using co-base system. Furthermore, the mono-alkylated bicyclic lactam and starting lactam were examined, providing the corresponding arylative ring opening product.

(II) Project 2

Schulzeines were natural products isolated from the marine sponge by Fusetani and co-workers in 2004. These alkaloids were found to inhibit α-glucosidase and viral neuraminidase. It should be noted that desulfated schulzeines could also inhibit the enzyme. The key step in our synthesis design is the formal [3+3] aza-annulation to construct the 1,2-piperidinone nucleus. After a series of reaction optimizations, we found that the best conditions for the formal [3+3] aza-annulation is using acrylic acid as the three-carbon donor and p-xylene as the solvent, thus establishing the tricyclic framework in a highly convergent manner. Through a two-step sequence comprising an alkene reduction and -amination reaction, we completed a formal total synthesis of schulzeine C. Our efforts toward the synthesis of desulfated schulzeine C and related synthetic derivative will also be discussed.

摘要 I
Abstract II
謝誌 III
Abbreviation IV
Contents VI
List of scheme VIII
List of table IX
List of figure X
Project 1 I
1.1 Introduction 1
1.1.1 General Information of Bicyclic Lactam 1
1.1.2 Preparation of Bicyclic Lactams 2
1.1.3 Stereoselectivity of Alkylation 2
1.1.4 Application of Bicyclic Lactams 3
1.1.5 Application of Natural Products 6
1.1.6 Motivation 9
1.2 Results and Discussions 10
1.2.1 Optimization of Reaction Conditions 10
1.2.2 New Reactivity of Meyers’ Lactam 14
1.2.3 Test of Monoalkylated Lactam and Non-Substituted Lactam 19
1.3 Conclusion 21
1.4 Experimental 22
1.5 Reference 30
Project 2 31
2.1 Introduction 32
2.1.1 Background of Schulzeine 32
2.1.2 Previous Research 32
2.1.3 Background of formal [3+3] cycloaddition 35
2.1.4 Motivation 37
2.2 Results and Discussions 38
2.2.1 Preparation of Dihydroquinoline 38
2.3 Conclusion 43
2.4 Experimental 44
Appendix 52

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11.周主恩，碩士論文，國立交通大學，2017