Giguère Denis, Sato Sachiko, St-Pierre Christian, Sirois Suzanne, Roy René
Departement of Chemistry, Université du Québec à Montréal, PO Box 8888, Succ. Centre-Ville Montreal, Québec, Canada H3C 3P8.
Bioorg Med Chem Lett. 2006 Mar 15;16(6):1668-72. doi: 10.1016/j.bmcl.2005.12.010. Epub 2006 Jan 5.
Phase transfer catalyzed reaction was used for the high yielding synthesis of aryl 1-thio-beta-d-galacto- and lacto-pyranosides carrying a panel of substituents on the phenyl groups. Best galectin-1 inhibitors were simple p-nitrophenyl thiogalactoside 5a for the monosaccharide and o-nitrophenyl thiolactoside 6f or napthylsulfonyl lactoside 8c, both being 20 times better relative to natural ligands. Relative inhibitory properties as low as 2500 and 40 microM were observed, respectively. The electronic effects of the lactoside aglycons directly influenced the electrostatic potential at O-3, which was associated with the inhibitory potencies against galectin-1.
相转移催化反应被用于高产率合成在苯基上带有一系列取代基的芳基 1-硫代-β-D-半乳糖吡喃糖苷和乳糖吡喃糖苷。最佳的半乳糖凝集素-1 抑制剂对于单糖而言是简单的对硝基苯基硫代半乳糖苷 5a，对于乳糖而言是邻硝基苯基硫代乳糖苷 6f 或萘基磺酰基乳糖苷 8c，二者相对于天然配体的活性均高出 20 倍。分别观察到低至 2500 和 40 μM 的相对抑制特性。乳糖苷苷元的电子效应直接影响 O-3 处的静电势，这与对半乳糖凝集素-1 的抑制效力相关。
