Synthesis and biological evaluation of a new sialyl Lewis X mimetic derived from lactose
Synthesis and biological evaluation of a new sialyl Lewis X mimetic derived from lactose
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DOI：
10.1021/jo025579t
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发表时间：
2002-08-09
影响因子：
3.6
通讯作者：
Koreeda, M
中科院分区：
文献类型：
--
作者：
Chervin, SM;Lowe, JB;Koreeda, M
以D-乳糖为原料，经14步反应合成了唾液酸化路易斯X(Sle(X))类化合物2-三甲基硅基乙基3-O-carboxymethyl-beta-D-galactopyranosyl-(1-->；4)-[alpha-L-fucosul-(1-->；6)]beta-D-glucopyranoside(2a)。这种合成的特点是在Koenigs-Knorr序列中使用活化的糖基化供体乳糖基碘，在半乳糖部分的C-3位进行区域选择性衍生化，以及立体选择性地构建岩藻糖-α(1->；6)-乳糖键。在剪应力条件下，测试了该模拟物抑制人多形核白细胞(HPMNL)与固定化重组人E-选择素的黏附能力。
A sialyl Lewis X (sLe(x)) mimetic compound, 2-(trimethylsilyl)ethyl 3-O-carboxymethyl-beta-D-galactopyranosyl-(1-->4)-[alpha-L-fucosul-(1-->6)]beta-D-glucopyranoside (2a), lids been synthesized in 14 steps from D-lactose. This synthesis features the use of the activated glycosylating donor, lactosyl iodide, in a Koenigs-Knorr sequence, the regioselective derivatization at the C-3 position of the galactose moiety, and the stereoselective construction of a fucose-alpha(1-->6)-lactose linkage. The mimetic was tested for its ability to inhibit human polymorphonuclear leukocyte (hPMNL) adhesion to immobilized recombinant human E-selectin under shear stress conditions.