UPMC Univ Paris 06, Institut Parisien de Chimie Moléculaire, UMR CNRS 7201, C-181, 4 place Jussieu F-75005 Paris, France.
Bioorg Med Chem. 2012 Jan 15;20(2):641-9. doi: 10.1016/j.bmc.2010.09.053. Epub 2010 Oct 1.
Noeuromycin is a highly potent albeit unstable glycosidase inhibitor due to its hemiaminal function. While stable D-gluco-like analogs have been reported, no data are available for D-manno-like structures. A series of tri- and tetrahydroxylated seven-membered iminosugars displaying either a D-manno-or a L-gulo-like configuration, were synthesized from methyl α-D-mannopyranoside using a reductive amination-mediated ring expansion as the key step. Screening towards a range of commercial glycosidases demonstrated their potency as competitive glycosidase inhibitors while cellular assay showed selective albeit weak glycoprotein processing mannosidase inactivation.
诺厄霉素是一种高效但不稳定的糖苷酶抑制剂，因为它具有半缩醛胺功能。虽然已经报道了稳定的 D-葡萄糖类似物，但没有关于 D-甘露糖类似物结构的数据。一系列三羟基和四羟基的七元亚氨基糖，具有 D-甘露糖或 L-古洛糖样构象，是从甲基 α-D-甘露吡喃糖苷出发，通过还原胺介导的环扩张作为关键步骤合成的。对一系列商业糖苷酶的筛选表明，它们是有效的竞争性糖苷酶抑制剂，而细胞测定表明它们选择性地但较弱地抑制糖蛋白加工甘露糖苷酶失活。
