Shih Tzenge-Lien, Liang Ming-Tsung, Wu Kuen-Da, Lin Chun-Hung
Department of Chemistry, Tamkang University, Tamsui 25137, Taipei County, Taiwan.
Carbohydr Res. 2011 Feb 1;346(2):183-90. doi: 10.1016/j.carres.2010.11.014. Epub 2010 Nov 19.
An effective synthetic method for polyhydroxylated azepanes that contain an alkyl group (Me or Bu) at either the 7- or N-positions is developed. The synthetic routes are accomplished in eight to ten steps from d-(-)-quinic acid. Among the compounds synthesized, the polyhydroxy 7-butyl azepane (compound 3), which possessed the R-configuration at C-7 position, is shown to give potent inhibition against β-galactosidase (IC(50)= 3 microM). Preliminary biological data indicate that the length of alkyl groups along with the proper stereochemistry at the C-7 position is essential for acquiring extra binding affinity. Using similar synthetic routes, the polyhydroxy N-methyl and N-butyl azepanes are synthesized for the comparison of their biological activities.
开发了一种有效的合成方法，用于制备在7位或N位含有烷基（甲基或丁基）的多羟基氮杂环庚烷。合成路线从d-(-)-奎尼酸开始，经过八到十个步骤完成。在合成的化合物中，在C-7位具有R构型的多羟基7-丁基氮杂环庚烷（化合物3）对β-半乳糖苷酶表现出强效抑制作用（IC(50)= 3 microM）。初步生物学数据表明，C-7位烷基链的长度以及适当的立体化学结构对于获得额外的结合亲和力至关重要。使用类似的合成路线，合成了多羟基N-甲基和N-丁基氮杂环庚烷以比较它们的生物活性。
