New glucuronic acid donors for the modular synthesis of heparan sulfate oligosaccharides.
New glucuronic acid donors for the modular synthesis of heparan sulfate oligosaccharides.
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DOI：
10.1039/c3ob42312c
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发表时间：
2014-04-07
影响因子：
3.2
通讯作者：
Boons GJ
中科院分区：
文献类型：
--
作者：
Dhamale OP;Zong C;Al-Mafraji K;Boons GJ
尽管数百种硫酸肝素（HS）结合蛋白参与了无数的生理和病理过程，但关于这些蛋白结合和介导生物活性所需配体的信息知之甚少。我们在这里报告了一种简化的方法来制备模块化双糖构建块，这将有利于HS低聚糖文库的组装，用于结构-活性关系的研究。特别是，我们发现葡萄糖醛酸供体通常在糖基化中表现不佳，当C-2羟基被永久的4-乙酰氧基-2,2-二甲基丁醇基- (PivOAc)或临时乙酰丙烯基（Lev）酯保护，C-4羟基被选择性可去除的2-甲基萘基（Nap）醚修饰时，可以得到高收率的偶联产物。研究表明，PivOAc酯可以在不影响硫酸盐酯的情况下被去除，使其成为HS低聚糖组装的理想保护基团。伊杜醛酸供体具有更有利的糖基供体特性，在C-2上有Lev酯保护的化合物和在C-4羟基上有Fmoc功能的化合物产生了高收率的偶联产物。新的供体避免糖基化后氧化，因此可以方便地制备模块化双糖构建块。
Although hundreds of heparan sulfate (HS) binding proteins have been implicated in a myriad of physiological and pathological processes, very little information is known about ligand requirements for binding and mediating biological activities by these proteins. We report here a streamlined approach for the preparation of modular disaccharide building blocks that will facilitate the assembly of libraries of HS oligosaccharides for structure-activity relationship studies. In particular, we have found that glucuronic acid donors, which usually perform poorly in glycosylations, can give high yields of coupling product when the C-2 hydroxyl is protected with a permanent 4-acetoxy-2,2-dimethyl butanoyl- (PivOAc) or temporary levulinoyl (Lev) ester and the C-4 hydroxyl modified with a selectively removable 2-methylnaphthyl (Nap) ether. It has been shown that the PivOAc ester can be removed without affecting sulfate esters making it an ideal protecting group for HS oligosaccharide assembly. Iduronic acid donors exhibit more favorable glycosyl donating properties and a compound protected with a Lev ester at C-2 and an Fmoc function at the C-4 hydroxyl gave coupling products in high yield. The new donors avoid post-glycosylation oxidation and therefore allow the facile preparation of modular disaccharide building blocks.
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DOI：
10.1016/b978-0-12-396527-1.00003-6
发表时间：
2012
影响因子：
--
作者：
Dulaney, Steven B.;Huang, Xuefei
通讯作者：
Huang, Xuefei
影响因子：
1.8
作者：
DAVIS, NJ;FLITSCH, SL
通讯作者：
FLITSCH, SL
影响因子：
15
作者：
Arungundram, Sailaja;Al-Mafraji, Kanar;Asong, Jinkeng;Leach, Franklin E., III;Amster, I. Jonathan;Venot, Andre;Turnbull, Jeremy E.;Boons, Geert-Jan
通讯作者：
Boons, Geert-Jan
影响因子：
15
作者：
Polat, Tuelay;Wong, Chi-Huey
通讯作者：
Wong, Chi-Huey
影响因子：
1.8
作者：
Dilhas, A;Bonnaffé, D
通讯作者：
Bonnaffé, D