新型3-O-糖基-3-去甲基秋水仙碱作为甘氨酸和γ-氨基丁酸受体的配体

Novel 3-O-glycosyl-3-demethylthiocolchicines as ligands for glycine and gamma-aminobutyric acid receptors.

作者信息

Gelmi Maria Luisa, Fontana Gabriele, Pocar Donato, Pontremoli Guido, Pellegrino Sara, Bombardelli Ezio, Riva Antonella, Balduini Walter, Carloni Silvia, Cimino Mauro

机构信息

Istituto di Chimica Organica "A. Marchesini", Facoltà di Farmacia, Università di Milano, Via Venezian 21, 20133 Milano, Italy.

出版信息

J Med Chem. 2007 May 3;50(9):2245-8. doi: 10.1021/jm061056s. Epub 2007 Apr 6.

DOI:10.1021/jm061056s

PMID:17411024

Abstract

New 3-O-glycosyl-3-demethylthiocolchicines containing natural and unnatural sugar moieties were prepared and tested on gamma-aminobutyric acid (GABA) and strychnine-sensitive glycine receptors present in rat brain and spinal cord. Two different synthetic approaches were used with the readily available 3-O-demethylthiocolchicine (1b) and thiocolchicoside (2a). Glycosyl compounds 2a-g were obtained from 1b and 1-fluorosugars 4. 6'-Heterosubstituted glycosyl compounds 6-12 and the 6'-desoxy derivative 2h were prepared from 2a.

摘要

制备了含有天然和非天然糖部分的新型3 - O - 糖基 - 3 - 去甲基秋水仙碱，并在大鼠脑和脊髓中存在的γ - 氨基丁酸（GABA）和士的宁敏感甘氨酸受体上进行了测试。使用两种不同的合成方法，以易于获得的3 - O - 去甲基秋水仙碱（1b）和秋水仙糖苷（2a）为原料。糖基化合物2a - g由1b和1 - 氟糖4制得。6'- 杂取代糖基化合物6 - 12和6'- 脱氧衍生物2h由2a制备。