Mandhapati Appi Reddy, Rajender Salla, Shaw Jonathan, Crich David
Department of Chemistry, Wayne State University, Detroit, MI 48202 (USA) http://chem.wayne.edu/crichgroup.
Angew Chem Int Ed Engl. 2015 Jan 19;54(4):1275-8. doi: 10.1002/anie.201409797. Epub 2014 Nov 28.
The preparation of a crystalline, peracetyl adamantanyl thiosialoside donor protected by an isothiocyanate group is described. On activation at -78 °C in the presence of typical carbohydrate acceptors, this donor gives high yields of the corresponding sialosides with exquisite α-selectivity. The high selectivity extends to the 4-O-benzyl-protected 3-OH acceptors, which are typically less reactive and selective than galactose 3,4-diols. Treatment of the α-sialosides with tris(trimethylsilyl)silane or allyltris(trimethylsilyl)silane results in replacement of the C5-N5 bond by a C-H or a C-C bond. The reaction of the isothiocyanate-protected sialosides with thioacids generates amides, while reaction with an amine gives a thiourea, which can be converted into a guanidine. The very high α-selectivities observed with the new donor and the rich chemistry of the isothiocyante function considerably extend the scope for optimization at the sialoside 5-position.
本文描述了一种由异硫氰酸酯基团保护的结晶性全乙酰化金刚烷硫代唾液酸苷供体的制备方法。在典型的碳水化合物受体存在下于-78°C活化时，该供体能以极高的α选择性高产率得到相应的唾液酸苷。这种高选择性也适用于4-O-苄基保护的3-OH受体，这类受体通常比半乳糖3,4-二醇的反应性和选择性更低。用三（三甲基硅基）硅烷或烯丙基三（三甲基硅基）硅烷处理α-唾液酸苷会导致C5-N5键被C-H键或C-C键取代。异硫氰酸酯保护的唾液酸苷与硫代酸反应生成酰胺，与胺反应则生成硫脲，硫脲可转化为胍。新供体所观察到的极高α选择性以及异硫氰酸酯官能团丰富的化学反应性极大地扩展了唾液酸苷5位的优化范围。
