Li Xiaoning, Huang Lijun, Hu Xiche, Huang Xuefei
Department of Chemistry, The University of Toledo, 2801 W. Bancroft Street, MS 602, Toledo, OH 43606.
Org Biomol Chem. 2009 Jan 7;7(1):117-27. doi: 10.1039/b813048e. Epub 2008 Oct 20.
Three series of thioglycosyl donors differing only in their respective aglycon substituents within each series have been prepared as representatives of typical glycosyl donors. The relative anomeric reactivities of these donors were quantified under competitive glycosylation conditions with various reaction time, promoters, solvents and acceptors. Over three orders of magnitude reactivity difference were generated by simple transformation of the para-substituent on the aglycon with methanol as the acceptor, while chemoselectivities became lower with carbohydrate acceptors. Excellent linear correlations were attained between relative reactivity values of donors and sigma(p) values of the substituents in the Hammett plots. This indicates that the glycosylation mechanism remains the same over a wide range of reactivities and glycosylation conditions. The negative slopes of the Hammett plots suggested that electron donating substituents expedite the reactions and the magnitudes of slopes can be rationalized by neighboring group participation as well as electronic properties of the glycon protective groups. Within the same series of donors, less nucleophilic acceptors gave smaller slopes in their Hammett plots. This is consistent with the notion that acceptor nucleophilic attack onto the reactive intermediate is part of the rate limiting step of the glycosylation reaction.
已制备了三组硫代糖基供体，每组内仅其各自的苷元取代基不同，作为典型糖基供体的代表。在不同反应时间、促进剂、溶剂和受体的竞争性糖基化条件下，对这些供体的相对端基异构反应活性进行了定量。以甲醇为受体，通过简单改变苷元上的对取代基，产生了超过三个数量级的反应活性差异，而对于糖类受体，化学选择性则较低。在哈米特图中，供体的相对反应活性值与取代基的σ(p)值之间获得了良好的线性相关性。这表明在广泛的反应活性和糖基化条件下，糖基化机制保持不变。哈米特图的负斜率表明供电子取代基加速了反应，并且斜率的大小可以通过邻基参与以及糖苷保护基的电子性质来解释。在同一组供体中，亲核性较低的受体在其哈米特图中的斜率较小。这与受体对反应中间体的亲核攻击是糖基化反应限速步骤的一部分这一观点一致。
