Piperidine analogues of D-galactose as potent inhibitors of α-galactosidase:: Synthesis by stannane-mediated hydroxymethylation of 5-azido-1,4-lactones.: Structural relationships between D-galactosidase and L-rhamnosidase inhibitors
Piperidine analogues of D-galactose as potent inhibitors of α-galactosidase:: Synthesis by stannane-mediated hydroxymethylation of 5-azido-1,4-lactones.: Structural relationships between D-galactosidase and L-rhamnosidase inhibitors
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DOI：
10.1039/a904145a
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发表时间：
1999-10-07
期刊：
影响因子：
--
通讯作者：
Fleet, GWJ
中科院分区：
文献类型：
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作者：
Shilvock, JP;Nash, RJ;Fleet, GWJ
本文报道了多羟基哌啶脱氧半乳糖吉里霉素2、同型半乳糖吉里霉素7和9以及其他2,6-亚氨基庚醇衍生物的合成，包括l -丙酮糖的类似物。5-叠氮酮-1,4-内酯通过加入羟基甲基锂18进行链延伸，得到叠氮基内酯，这是由受保护的锡基甲醇衍生物17金属化生成的。氢化反应导致叠氮化物的还原，随后的分子内还原性胺化反应得到哌啶环体系。去保护的亚氨基半乳糖糖类似物是有效的和选择性的α -半乳糖苷酶抑制剂。对α -半乳糖苷酶对柚皮苷酶（l -鼠李糖苷酶）抑制选择性的结构特征的观察也有报道。
The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono-1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogenation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective alpha-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of alpha-galactosidases over naringinase (L-rhamnosidase) are also reported.