設計與合成具有咪唑啉取代之新型雙環亞胺醣

自天然物分離的亞胺醣結構，具有多樣化的生物活性表現，包含癌症的治療、病毒的拮抗及細菌的抑制等…，是極具藥效潛力的分子結構。由於天然亞胺醣分子的種類以及數量有限；化學家受到天然的亞胺醣結構啟發，透過設計、合成及官能基的轉換，建立新型亞胺醣結構，豐富這個領域的研究。　　天然的亞胺醣結構存在眾多的生物活性表現，其中以抑制醣解酶生物活性的表現最為出色。而具有雙環結構的亞胺醣分子，被視為是最有潛力的一種類型。由於雙環結構亞胺醣存在剛性表現，分子不易產生扭轉，因此醣解酶在進行水解的過程中結構不容易改變，因而與醣解酶作用端之間的鍵結不易受到外力影響。　　本論文參考了實驗室過去所設計、合成新型亞胺醣結構的研究，包含以五環的亞胺醣 (Polyhydroxylated piperidine) 為骨架，合成具備雜環結構 (Triazole/-Isoxazole) 的研究，與合成新型五五環雙環亞胺醣結構 (Polyhydroxylated pyrrolizidine) 和其分子群的實驗。　　透過我們實驗室設計的合成途徑，將能讓不同種類的戊醣在相同的合成條件下，形成各種構型相同，但具備不同羥基立體位相的六環亞胺醣中間體 (Polyhydroxylated piperidine)。而後利用中間體具備的二胺基結構，與活化自氰類結構的亞胺酯鹽(Imidate salt)，進行雜環-咪唑啉 (Imidazoline) 的合成，成功得到同時具有雜環與雙環特徵的新型雙環亞胺醣結構。

關鍵字

亞胺醣；雙環亞胺醣；咪唑啉

並列摘要

Iminosugars possess diverse bioactivities which have significant therapeutic potential that includes treatment of cancers, bacterial suppression, antagonists of viruses, and treatments of metabolic diseases. Among these bioactivities of iminosugars, the inhibition of glycosidase in treatments of metabolic diseases is very noticeable. Protonated iminosugars are regarded as the transition state mimicing the oxocarbenium ion during the enzymatic hydrolysis of glycosidase. Inspired by these versatile bioactivities and structures of iminosugars, scientists have tried to design and transform the functional groups to build novel structure of iminosugars. In this project, our lab designed a practical synthetic approach of preparing a novel structure of an iminosugar. In this synthetic approach we can use different kinds of pentose to make diamine intermediates with different hydroxyl configurations. Hydroxyl chloride and methanol were used to activate the benzonitrile to methyl benzimidate hydrochloride. Imidate salt was then cyclized with diamine iminosugar intermediates to obtain a novel iminosugar that has heterocyclic and bicyclic structural properties.

並列關鍵字

iminosudar ； bicyclic imisugar ； azasugar ； imidazoline

參考文獻

9. (a) Tsou, E. L.; Yeh, Y. T.; Liang, P. H., Cheng, W. C., A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP. Tetrahedron 2009, 65, 93-100. (b). Chan, T. H.; Chang, Y. F.; Hsu, J. J.; Cheng, W. C., Straightforward Synthesis of Diverse 1-Deoxyazapyranosides via Stereocontrolled Nucleophilic Additions to Six-Membered Cyclic Nitrones. Tetrahedron 2010, 29, 5555-5559.

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國際替代計量

設計與合成具有咪唑啉取代之新型雙環亞胺醣

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