Painter Gavin F, Eldridge Paul J, Falshaw Andrew
Carbohydrate Chemistry, Industrial Research Limited, PO Box 31-310, Lower Hutt, New Zealand.
Bioorg Med Chem. 2004 Jan 2;12(1):225-32. doi: 10.1016/j.bmc.2003.10.003.
Two pairs of C(2)-symmetric tetrahydroxyazepanes [(-), (+)-1 and (-), (+)-2] have been synthesized from the enantiomeric chiro-inositols and evaluated as glycosidase inhibitors. Alternative syntheses of ido-tetrahydroxyazepanes (-)- and (+)-2 from myo-inositol were also developed. The key synthetic transformations were glycol fission and cyclization of the derived dialdehydes by double reductive amination. The D-manno-tetrahydroxyazepane [(-)-1] showed selective inhibition of alpha-L-fucosidase and beta-D-galactosidase, while the enantiomer [(+)-1] was a selective inhibitor of an alpha-D-galactosidase. In contrast, the L-ido-tetrahydroxyazepane (+)-2 was a broad spectrum hexosidase inhibitor, but showed none of the reported hexosaminidase inhibition. Its enantiomer (-)-2 is a poor hexosidase inhibitor.
已从对映体手性肌醇合成了两对具有C(2)对称性的四羟基氮杂环庚烷[(-),(+)-1和(-),(+)-2]，并将其作为糖苷酶抑制剂进行了评估。还开发了从肌醇合成异-四羟基氮杂环庚烷(-)-和(+)-2的替代方法。关键的合成转化是二醇裂解以及通过双重还原胺化使衍生的二醛环化。D-甘露糖型四羟基氮杂环庚烷[(-)-1]对α-L-岩藻糖苷酶和β-D-半乳糖苷酶具有选择性抑制作用，而对映体[(+)-1]是α-D-半乳糖苷酶的选择性抑制剂。相比之下，L-异-四羟基氮杂环庚烷(+)-2是一种广谱己糖苷酶抑制剂，但未表现出已报道的对氨基己糖苷酶的抑制作用。其对映体(-)-2是一种较差的己糖苷酶抑制剂。
