Carbohydrate Chemistry Team, Industrial Research Limited, PO Box 31-310, 5040 Lower Hutt, New Zealand.
Carbohydr Res. 2010 Jul 2;345(10):1371-6. doi: 10.1016/j.carres.2010.04.015. Epub 2010 Apr 24.
Cyclization by double reductive amination of d-xylo-hexos-5-ulose with methyl 6-aminohexanoate gave (methoxycarbonyl)pentyl-1-deoxynojirimycin. Reaction of the terminal carboxylic acid with N-dansyl-1,6-diaminohexane provided the corresponding chain-extended fluorescent derivative. By reaction with bis(6-dansylaminohexyl)amine, the corresponding branched di-N-dansyl compound was obtained. Both compounds are strong inhibitors of d-glucosidases and could also be shown to distinctly improve, at sub-inhibitory concentrations, the activity of beta-glucocerebrosidase in a Gaucher fibroblast (N370S) cell-line through chaperoning of the enzyme to the lysosome.
用甲基 6-氨基己酸对 d-木糖-5-戊酮进行双还原胺化环化，得到（甲氧基羰基）戊基-1-去氧野尻霉素。末端羧酸与 N-丹磺酰基-1,6-二氨基己烷反应，提供相应的链延伸荧光衍生物。通过与双（6-丹磺酰氨基己基）胺反应，得到相应的支化双 N-丹磺酰基化合物。这两种化合物都是 d-葡萄糖苷酶的强抑制剂，并且还可以通过将酶伴侣到溶酶体中，在亚抑制浓度下明显提高 Gaucher 成纤维细胞（N370S）细胞系中β-葡糖脑苷脂酶的活性。
