Li Xiaona, Di Carluccio Cristina, Miao He, Zhang Lvfeng, Shang Jintao, Molinaro Antonio, Xu Peng, Silipo Alba, Yu Biao, Yang You
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Shanghai Key Laboratory of New Drug Design, Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, 80126, Napoli, Italy.
Angew Chem Int Ed Engl. 2023 Oct 23;62(43):e202307851. doi: 10.1002/anie.202307851. Epub 2023 Jul 20.
Cyclodextrins are widely used as carriers of small molecules for drug delivery owing to their remarkable host properties and excellent biocompatibility. However, cyclic oligosaccharides with different sizes and shapes are limited. Cycloglycosylation of ultra-large bifunctional saccharide precursors is challenging due to the constrained conformational spaces. Herein we report a promoter-controlled cycloglycosylation approach for the synthesis of cyclic α-(1→6)-linked mannosides up to a 32-mer. Cycloglycosylation of the bifunctional thioglycosides and (Z)-ynenoates was found to be highly dependent on the promoters. In particular, a sufficient amount of a gold(I) complex played a key role in the proper preorganization of the ultra-large cyclic transition state, providing a cyclic 32-mer polymannoside, which represents the largest synthetic cyclic polysaccharide to date. NMR experiments and a computational study revealed that the cyclic 2-mer, 4-mer, 8-mer, 16-mer, and 32-mer mannosides adopted different conformational states and shapes.
由于具有卓越的主体性质和出色的生物相容性，环糊精被广泛用作小分子药物递送的载体。然而，不同尺寸和形状的环状寡糖种类有限。由于构象空间受限，超大双功能糖前体的环化糖基化具有挑战性。在此，我们报道了一种由启动子控制的环化糖基化方法，用于合成高达32聚体的环状α-(1→6)-连接甘露糖苷。发现双功能硫代糖苷和(Z)-烯炔酸酯的环化糖基化高度依赖于启动子。特别是，足量的金(I)配合物在超大环状过渡态的适当预组织中起关键作用，从而得到环状32聚体聚甘露糖苷，这是迄今为止最大的合成环状多糖。核磁共振实验和计算研究表明，环状2聚体、4聚体、8聚体、16聚体和32聚体甘露糖苷具有不同的构象状态和形状。
