Bioorganic Synthesis Department, Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
Angew Chem Int Ed Engl. 2018 Jul 2;57(27):8240-8244. doi: 10.1002/anie.201802899. Epub 2018 Apr 26.
The reactivity of both coupling partners-the glycosyl donor and acceptor-is decisive for the outcome of a glycosylation reaction, in terms of both yield and stereoselectivity. Where the reactivity of glycosyl donors is well understood and can be controlled through manipulation of the functional/protecting-group pattern, the reactivity of glycosyl acceptor alcohols is poorly understood. We here present an operationally simple system to gauge glycosyl acceptor reactivity, which employs two conformationally locked donors with stereoselectivity that critically depends on the reactivity of the nucleophile. A wide array of acceptors was screened and their structure-reactivity/stereoselectivity relationships established. By systematically varying the protecting groups, the reactivity of glycosyl acceptors can be adjusted to attain stereoselective cis-glucosylations.
两种偶联伙伴（糖基供体和受体）的反应性对于糖基化反应的结果（包括产率和立体选择性）具有决定性意义。尽管糖基供体的反应性已经得到很好的理解，并且可以通过对功能/保护基模式的操作来控制，但糖基受体醇的反应性却了解甚少。在这里，我们提出了一种操作简单的系统来评估糖基受体的反应性，该系统使用了两种具有立体选择性的构象锁定供体，而立体选择性则取决于亲核试剂的反应性。对大量的受体进行了筛选，并确定了它们的结构-反应性/立体选择性关系。通过系统地改变保护基，可以调节糖基受体的反应性，从而实现立体选择性的顺式葡萄糖基化。
