利用D-(-)-Quinic acid合成7-(Hydroxymethyl)thiepane-3,4,5-triols

The First and Facile Synthesis of 7-(Hydroxymethyl)thiepane-3,4,5-triols from D-(-)-Quinic acid.

高維麟(Wei-Lin Gao)

指導教授 ： 施增廉

淡江大學/理學院/化學學系碩士班/碩士(2012年)

https://doi.org/10.6846/TKU.2012.00646

摘要

醣水解酵素是生物體代謝循環中不可缺少的一環，它與許多疾病都有密切的關係，如: 癌症，糖尿病和HIV等等。科學家以醣水解酵素活性區為目標，設計出一系列醣水解酵素抑制劑。
自從1961年，含硫醣類化合物的合成以五員環與六員環含硫醣類化合物為主流，後來發現七員環的結構更具靈活性，陸續的也被合成。自從植物 Salacia reticulate分離出 salacinol後，發現是一兩性離子化合物，與醣水解酵素過渡態oxonium ion 結構有些相似，對於特定酵素也有不錯的抑制活性，所以此類 thiosugars之合成也被科學家所注意。
我們已合成出一系列7-(hydroxymethyl)-3,4,5-trihydroxyazepane，基於相同概念，本篇全合成主要以 D-(-)-Quinic acid為起始物，合成一系列不同立體位向之七員環 7-(hydroxymethyl)thiepane-3,4,5-triols。在研究過程中發現，化合物9 (tetrahydrothiepanes)可經自身重排得到六圓環化合物10 (tetrahydroxyhiopyrane)。

關鍵字

醣水解酵素抑制劑 ； 含硫醣類化合物 ； 七員硫環

並列摘要

Glycosidases play an important role in metabolism. Many diseases related to glycosidase, such as cancer, diabetes , HIV, etc.
In this article, the seven-memberd ring thiosugars, so-called thiepanes, were synthesized in order to evalute them as inhibitors. Their structures are more flexible than the other thiosugars such as thiopenes and thiopyranes. Salacinol isolated from Salacia reticulate, possessed zwitterionic structure which is similar to the oxonium ion. Many salacinol analogues were synthesized as glycosidase inhibitors and they showed great biological activities.
We have synthesized 7-(hydroxymethyl)-3,4,5-trihydroxyazepanes as potential glycosidase inhibiors. Based on the similar strategy, we synthesized a series of thiosugars, 7-(hydroxymethyl)thiepane-3,4,5-triols from D-(-)-quinic acid.

並列關鍵字

quinic acid ； glycosidase inhibitor ； thiosugar ； thiepanes

參考文獻

1.Davies, G. J.; Gloster, T. M.; Henrissant, B. Curr. Opin. Structure. Biol. 2005, 15, 637-645.

2.(a) Johnson, C. R.; Johns, B. A. J. Org. Chem. 1997, 62, 6046-6050. (b) Horii, S.; Fukase, H.; Matsuo, T.; Kameda, Y.; Asano, N.; Matsui, K. J. Med. Chem. 1986, 29, 1038-1046. (c) Humphries, M. J.; Matsumoto, K.; White, S. L.; Olden, K. Cancer Res. 1986, 46, 5215-5222. (d) Chery, F.; Cronin, L.; O’Brien, J. L.; Murphy, P. V. Tetrahedron, 2004, 60, 6597-6608.

3.Zechel, D. L.; Withers, S. G. Acc. Chem. Res. 2000, 33, 11-18.

5.Horii, S.; Kameda, Y. J. Chem. Soc., Chem. Commun. 1972, 747-748.

6.Mehta, G.; Lakshminath, S. Tetrahedron Lett. 2002, 43, 331-334.