合成7-Hydroxymethyl-3,4,5-trihydroxyazepanes、Polyhydroxyperhydroazaazulene醣水解酵素抑制劑

Synthesis of 7-Hydroxymethyl-3,4,5-trihydroxyazepanes and Polyhydroxyperhydroazaazulenes for glycosidase inhibitors

蔣呈凡(Cheng-Fang Chiang)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2007年)

https://doi.org/10.6846/TKU.2007.00786

摘要

根據許多文獻報導，azasugars具有抑制醣水解酵素之生物活性，可作為抗癌、抗糖尿病藥以及抗AIDS之藥物。

近年來研究發現，七圓環之azasugars (或稱為azepanes)，在結構上較五或六圓環之azasugars更具可變性(flexibility)，且更容易進入DNA的較小凹槽(DNA minor grove)，達到抑制效果。不具C2對稱之azepanes之合成在文獻上少有探討，於是我們以D-(-)-quinic acid為起始物，經過10個合成步驟，得到兩個新的7-Hydroxymethyl-3,4,5-trihydroxyazepanes標的物。並探討其立體化學對其抑制性的影響。

除此之外，最近有文獻報導，五七圓環bicyclic系統的azasugars (或稱為azaazulenes)，可能成為有潛力之醣水解酵素抑制劑。我們以trans-4-hydroxy-L-proline作為起始物，經過9個合成步驟，得到兩個新的polyhydroxyperhydroazaazulenes，並探討其抑制活性。

關鍵字

醣水解酵素 ； 醣水解酵素抑制劑

並列摘要

Azasugars are considered as glycosidase inhibitors and possess potential in treatment of diabetes, cancers, and AIDS.

Seven-membered azasugars were reported to be more conformationally flexible than the corresponding six- and five-membered counterparts, but little attention has been paid. We describe herein a new approach to the synthesis of diastereomeric 7-hydroxymethyl-3,4,5-trihydroxyazepanes in ten steps from D-(-)-quinic acid. We also compare the biological activities with C2-symmetrical tetrahydroxy
-azepanes.

In addition, 5,7-heterocyclic ring system of azasugars (called azaazulenes) are also considered to be potential glycosidase inhibitors. We have established an expeditious synthesis of newpolyhydroxyperhydroazaazulenes from trans-4-hydroxy-L-proline.

並列關鍵字

Azasugars ； Azepanes ； Azaazulenes ； Glycosidase inhibitors ； Polyhydroxyperhydroazaazulenes ； Tetrahydroxyazepanes

參考文獻

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