SYNTHESIS OF 5-AMINO-5-DEOXY-D-GALACTOPYRANOSE AND 1,5-DIDEOXY-1,5-IMINO-D-GALACTITOL, AND THEIR INHIBITION OF ALPHA-AND BETA-D-GALACTOSIDASES
SYNTHESIS OF 5-AMINO-5-DEOXY-D-GALACTOPYRANOSE AND 1,5-DIDEOXY-1,5-IMINO-D-GALACTITOL, AND THEIR INHIBITION OF ALPHA-AND BETA-D-GALACTOSIDASES
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DOI：
10.1016/s0008-6215(00)90138-1
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发表时间：
1986-11-01
影响因子：
3.1
通讯作者：
POHL, S
中科院分区：
文献类型：
--
作者：
LEGLER, G;POHL, S
提出了从1,2:5,6-二-O-异亚丙基-α-D-呋喃葡萄糖开始制备标题化合物及其L-altro类似物的12步路线。它们的合成基于用雷尼镍还原L-阿拉伯-呋喃己糖-5-乌糖的受保护的5-羟基亚氨基衍生物，并对D-呋喃半乳糖衍生物的制备进行了以下改进：用重铬酸吡啶鎓-乙酸酐在C-3处氧化，将3-O-乙酰基-己-3-烯呋喃糖中间体立体定向还原为D-gulo衍生物，并在其C-3处反转3-甲苯磺酸酯与乙酸四丁基铵在氯苯中反应。来自咖啡豆和大肠杆菌的α-D-半乳糖苷酶以及来自大肠杆菌和温氏曲霉的β-D-半乳糖苷酶被抑制，Ki值范围为0.0007至8.2μM。与D-半乳糖类似物形成酶-抑制剂复合物的时间尺度为分钟，而D-半乳糖醇类似物显示仅用来自咖啡豆的α-D-半乳糖苷酶和来自A.gentii的β-D-半乳糖苷酶缓慢达到抑制作用。除了来自大肠杆菌的β-D-半乳糖苷酶和来自杏仁的β-D-葡萄糖苷酶外，D-半乳糖醇类似物的N-烷基化对抑制是有害的，但是，即使使用这些酶，观察到的亲和力增强也比N-烷基化的D-半乳糖胺和D-葡萄糖胺的亲和力增强小102至103倍。
A 12-step route is presented starting from 1,2:5,6-di-O-isopropylidene-.alpha.-D-glucofuranose for the preparation of the title compounds and their L-altro analogues. Their synthesis is based on the reduction with Raney nickel of a protected 5-hydroxyimino derivative of L-arabino-hexofuranose-5-ulose, with the following improvements for the preparation of a D-galactofuranose derivative: oxidation at C-3 with pyridinium dichromate-acetic anhydride, stereospecific reduction of a 3-O-acetyl-hex-3-enofuranose intermediate to the D-gulo derivative, and inversion at C-3 of its 3-tosylate with tetrabutylammonium acetate in chlorobenzene. .alpha.-D-Galactosidase from coffee beans and from Escherichia coli and .beta.-D-galactosidase from E. coli and Aspergillus wentii were inhibited with Ki values that ranged from 0.0007 to 8.2 .mu.M. Formation of the enzyme-inhibitor complexes with the D-galactose analogue was on the time-scale of minutes, whereas the D-galactitol analogue showed a slow approach to the inhibition only with .alpha.-D-galactosidase from coffee beans and .beta.-D-galactosidase from A. wentii. N-Alkylation of the D-galactitol analogue was detrimental to the inhibition except for .beta.-D-galactosidase from E. coli and .beta.-D-glucosidase from almonds, but, even with these enzymes, the observed affinity enhancements were 102 to 103-times smaller than those of N-alkylated D-galactosylamine and D-glucosylamine.