Shih Tzenge-Lien, Yang Ru-Ying, Li Shiou-Ting, Chiang Cheng-Fan, Lin Chun-Hung
Department of Chemistry, Tamkang University, Tamsui, Taipei County 25137, Taiwan.
J Org Chem. 2007 May 25;72(11):4258-61. doi: 10.1021/jo070058x. Epub 2007 May 5.
Several new stereoisomers of 3,4,6-trihydroxyazepanes and 7-hydroxymethyl-3,4,5-trihydroxyazepanes as well as known 3,4,5-trihydroxyazepanes were synthesized as potent glycosidase inhibitors from D-(-)-quinic acid in an efficient manner. The key step employs dihydroxylation of protected chiral 1,4,5-cyclohex-2-enetriols under RuCl3/NaIO4/phosphate buffer (pH 7) condition, followed by reductive amino cyclization. We found the choice of an appropriate protecting group to C1-OH of chiral 1,4,5-cyclohex-2-enetriols would increase the yields of cyclization. The preliminary biological data indicate some of these azepanes possess potent inhibition against alpha-mannosidase and alpha-fucosidase.
以高效的方式从D-(-)-奎尼酸合成了几种新的3,4,6-三羟基氮杂环庚烷和7-羟甲基-3,4,5-三羟基氮杂环庚烷的立体异构体以及已知的3,4,5-三羟基氮杂环庚烷，作为有效的糖苷酶抑制剂。关键步骤是在RuCl3/NaIO4/磷酸盐缓冲液（pH 7）条件下对受保护的手性1,4,5-环己-2-烯三醇进行二羟基化，然后进行还原氨基环化。我们发现，对手性1,4,5-环己-2-烯三醇的C1-OH选择合适的保护基团会提高环化产率。初步生物学数据表明，其中一些氮杂环庚烷对α-甘露糖苷酶和α-岩藻糖苷酶具有强效抑制作用。
