Lennard-Jones Laboratory, School of Chemical and Physical Sciences, Keele University, Keele, Staffordshire ST5 5BG, UK.
Org Biomol Chem. 2019 Oct 30;17(42):9321-9335. doi: 10.1039/c9ob02053e.
Alginate, an anionic polysaccharide, is an important industrial biomaterial naturally harvested from seaweed. Many of its important physicochemical properties derive from the presence of charged carboxylate groups presented as uronic acids within the polysaccharide backbone. An ability to modify these carboxylates with alternate functional groups would enable the design and implementation of new alginate systems possessing different physicochemical properties. We present herein our approach to the chemical synthesis of alginate disaccharides, modified at the carboxylate C6 position with bioisosteric hydroxamate residues. The synthesis and utilisation of C6-hydroxamate donor and acceptor building blocks enables a first access to protected α- and β-linked hydroxamate-containing disaccharides, additionally equipped with a functional tether at the reducing terminus. The evaluation of these building blocks for chemical glycosylation demonstrates the incorporation of bioisosteric functional groups into an alginate disaccharide backbone and highlights the important contribution of both acceptor and donor reactivity underpinning uronate glycosylations.
藻酸盐是一种阴离子多糖，是一种从海藻中天然提取的重要工业生物材料。其许多重要的物理化学性质源于多糖主链中存在的带电荷的羧酸盐基团，表现为糖醛酸。能够用其他官能团修饰这些羧酸盐，将使设计和实施具有不同物理化学性质的新藻酸盐系统成为可能。本文介绍了我们在化学合成中对羧酸盐 C6 位置进行修饰的方法，即用生物等排体羟肟酸残基修饰藻酸盐二糖。C6-羟肟酸供体和受体砌块的合成和利用，使我们首次能够获得带有保护基的α-和β-连接的羟肟酸二糖，并且在还原末端还带有功能连接基团。对这些砌块进行化学糖基化的评估表明，生物等排体官能团已被引入藻酸盐二糖骨架中，并强调了糖基化中接受体和供体反应性的重要贡献。
