天然存在的或合成的亞氨基糖被認為可以模擬碳水化合物或其水解過渡態，從而可能有效地抑制特定酵素，在結構上這些含有吡咯烷或哌啶基序骨架的材料表現出廣泛的生物學特性，例如多羥基化吡咯烷和哌啶及其衍生物對各種糖加工酶具有有效和選擇性的抑制效果，這些醣加工酶與糖尿病、癌症、病毒感染和溶酶體貯積症等疾病有關，由於它們具有廣泛的生物活性，這些結構被認為是藥物設計的特殊骨架。
　　在本論文中具有兩個化學合成重點:（I）利用天然產物啟發的組合式化學（NPICC）作為關鍵策略去合成結構多樣化分子群和（II）使用非對映選擇性中間體2-1（環硝酮）合成兩個主要骨架2-13和2-14。對於結構多樣性，這兩種骨架通過組合化學與一系列取代的異氰酸酯分子進行平行合成反應，然後快速純化以方便地生成兩吡咯烷衍生物之分子群。
　　這一系列分子被應用於對(α-hGMII)高基氏體甘露糖苷酶的抑制研究，抑制此酵素被認為是一個有前途的N-聚醣調節靶點，篩選出幾個小分子如2-15用於對 Hemagglutinin 的N-糖蛋白進行 N-聚醣調節研究，通過 LC-MS/MS 分析發現2-15可以更好地減少複雜型聚醣並增加雜化型聚醣，此分子被認定為一種潛在的N-聚醣調節劑。
　　另一方面，這兩個分子群也被應用於細胞毒性研究，我們發現2-52 和 2-53 對 MCF7 等幾種癌細胞表現出一定的細胞毒性(EC50 ≈ 10 μM) ，與現行藥物Doxorubicin的特性相比，兩者都顯示出相對好的抗癌效果且對於正常細胞（如 MCF10A）的毒性更小。
　　這些結果致使我們對亞氨基糖應用產生新的思考，在建立了結構活性關係（SAR）分析後，我們計劃合成化學探針去找出它們對應的細胞結合劑，如酶或受體，以確定它們在抗癌效果作用的標靶。

Naturally occurring or synthetic iminosugars have been thought to mimic carbohydrates or their hydrolysis transition states, which allow to inhibit the targeting enzymes effectively. Structurally, these molecules containing the skeleton of a pyrrolidine or piperidine motif exhibit a wide range of biological properties. For example, polyhydroxylated pyrrolidines and piperidines and their derivatives have potent and selective inhibitory activities against various glycoprocessing enzymes that are involved in diseases such as diabetes and cancer, viral infections, and lysosomal storage disorders. Because of their broad-spectrum biological activities, these cores are considered privileged scaffolds for drug design.
　　In this thesis, two synthetic features are (I) Natural product-inspired combinatorial chemistry (NPICC) as a key strategy to generate structurally diverse libraries and (II) using the diastereoselective intermediate 2-1 (cyclic nitrone) to synthesize two main scaffolds 2-13 and 2-14. For the structural diversity, these two scaffolds are applied to parallelly react with a series of substituted isocyanate molecules via a combinatorial chemistry approach, followed by rapid purification to conveniently generate two pyrrolidine-based libraries (Library I and Library II).
These libraries were applied for the inhibition study against mannosidases. Among them, Golgi mannosidase II is thought as a promising N-glycan modulation target. Hit 2-15 was sieved out, followed by the N-glycan modulation study toward the N-glycoproteins of Hemagglutinin. Based on our results, 2-15 is qualified as a new N-glycan modulator to perform the better activity to reduce the complex typed glycans and increase hybrid typed glycans by LC-MS/MS analysis.
On the other hand, these two libraries were also applied for cytotoxicity studies. 2-52 and 2-53 exhibited certain cytotoxicity activity (EC50 ≈ 10 μM) against several cancer cell lines such as MCF7. Both showed better anticancer profiling, and less toxicity toward normal cells such as MCF10A, compared to the property of the first-line drug Doxorubicin.
These results guide us to a new thinking for iminosugar applications. Upon the structure activity relationship (SAR) analysis is established, we plan to synthesize chemical probes to fish out their corresponding cell binders such as enzymes or receptors toward anticancer cell lines to identify their primary targets in the future.

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