利用D-(-)-quinic acid合成3,4,6-trihydroxyazepanes及含有N-benzyl之衍生物作為具有潛力之醣水解酵素抑制劑

Transformation of D-(-)-quinic acid into 3,4,6-trihydroxyazepanes and their N-benzyl derivatives for potential glycosidase inhibitors.

楊如盈(Ju-Ying Yang)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2005年)

https://doi.org/10.6846/TKU.2005.00518

摘要

在天然物中，具五或六圓環之azasugars多為glycosidase之抑制劑。然而，近年來發現具七圓環結構的azasugars，即所謂的azepanes(polyhydroxyazepanes)，較前二類分子更有潛力發展成為糖尿病、抗HIV、抗病毒的藥物，因為其構形較五或六圓環之azasugars更易嵌入DNA之minor grove。
類似trihydroxyazepanes的分子在文獻上出現的次數並不多，本實驗以既便宜且易取得的D-(-)-quinic acid為起始物，共經10個反應步驟，得到一系列具有立體化學特異性的3,4,6-trihydroxyaze-panes標的物。藉由和tetrahydroxyazepanes之生物活性作比較，進而了解azasugars中官能基的位置、數目及立體化學對醣水解酵素抑制性的影響。

關鍵字

醣水解酵素抑制劑

並列摘要

The naturally occurring five- and six-membered azasugars are considered as glycosidase inhibitors. Most recently, the seven-membered azasugars(poly-hydroxyazepanes) were reported to have potential in treatment of diabetes, cancers and AIDS. These heterocycles are more flexible in conformation than the corresponding six- and five-membered counterparts and may bind in the minor groove of DNA.

Little attention has been given to trihydroxyazepanes. We wish to describe herein a new approach to the synthesis of diastereomeric azasugars (3,4,6-trihydroxyazepanes) in ten steps each from the commercially available D-(-)-quinic acid. The biological test of this series of 3,4,6-trihydroxyazepanes and their derivatives allows us to compare with their corresponding tetrahydroazepanes. Especially, we can further learn the structure relationship regarding to the stereochemistry of hydroxy groups.

並列關鍵字

Azasugars ； Azepanes ； Glycosidase inhibitors ； D-(-)-Quinic acid ； Polyhydroxyazepanes ； Trihydroxyazepanes.

參考文獻

1.Fuentes, J.; Olano, D.; Pradera, M. A. Tetrahedron Lett. 1999, 40, 4063-4066.

7.Withers, S. G.; Street, I. P. J. Am. Chem. Soc. 1988, 110, 8551-8553.

8.Johnson, C. R.; Johns, B. A. J. Org. Chem. 1997, 62, 6046-6050.

12.Painter, G. F.; Eldridge, P. J.; Falshaw, A. Bioorg. Med. Chem. 2004, 12, 225-232.

17.Paulsen, H.; Todt, K. Chem. Ber. 1967, 100, 512-520.