Laboratoire de Chimie Organique et Bioorganique, FRE3253, Ecole Nationale Supérieure de Chimie de Mulhouse, Université de Haute-Alsace., Mulhouse, France.
Bioorg Med Chem Lett. 2010 Dec 15;20(24):7410-3. doi: 10.1016/j.bmcl.2010.10.043. Epub 2010 Oct 15.
We here describe a simple and efficient synthetic method for a non-hydrolysable precursor of a GDP-fucose analogue: The synthesis of the racemic aminofuranofucitol 3 from sorbic alcohol by nitroso-Diels-Alder reaction. This 'all-cis-pyrrolidine', with all substituents occupying a cis position, has been determined as a potent inhibitor of α-L-fucosidase and a moderate inhibitor of α- and β-D-galactosidase. The good recognition of this fucose moiety analogue by specific enzymes is thus confirmed. The C-anomeric bond in this particular structure is in the β-position and makes this compound an interesting candidate for further chemical modifications. Influence of the methyl and hydroxymethyl groups on the inhibition potency is discussed.
我们在这里描述了一种 GDP-岩藻糖类似物的非水解前体的简单高效合成方法：通过亚硝-Diels-Alder 反应从山梨糖醇合成非对映异构体氨基呋喃岩藻糖醇 3。这种“全顺式吡咯烷”，所有取代基均占据顺式位置，已被确定为α-L-岩藻糖苷酶的有效抑制剂和α-和β-D-半乳糖苷酶的适度抑制剂。因此，证实了这种岩藻糖类似物被特定酶的良好识别。在这种特殊结构中，C-端糖苷键处于β 位置，这使得该化合物成为进一步化学修饰的有趣候选物。讨论了甲基和羟甲基对抑制效力的影响。
