Département de chimie, 1045 av. De la Médecine, Université Laval PROTEO, RQRM, Québec City, QC, G1V 0A6, Canada.
Nat Commun. 2018 Nov 9;9(1):4721. doi: 10.1038/s41467-018-06901-y.
The replacement of hydroxyl groups by fluorine atoms on hexopyranose scaffolds may allow access to the discovery of new chemical entities possessing unique physical, chemical and ultimately even biological properties. The prospect of significant effects generated by such multiple and controlled substitutions encouraged us to develop diverse synthetic routes towards the stereoselective synthesis of polyfluorinated hexopyranoses, six of which are unprecedented. Hence, we report the synthesis of heavily fluorinated galactose, glucose, mannose, talose, allose, fucose, and galacturonic acid methyl ester using a Chiron approach from inexpensive levoglucosan. Structural analysis of single-crystal X-ray diffractions and NMR studies confirm the conservation of favored C conformation for fluorinated carbohydrate analogs, while a slightly distorted conformation due to repulsive 1,3-diaxial F···F interaction is observed for the trifluorinated talose derivative. Finally, the relative stereochemistry of multi-vicinal fluorine atoms has a strong effect on the lipophilicities (logP).
在己糖骨架上的羟基被氟原子取代可能会发现具有独特物理、化学甚至生物性质的新化学实体。这种多取代和控制取代所产生的显著效果的前景鼓励我们开发了多种合成途径，以立体选择性合成多氟化己糖，其中有六种是前所未有的。因此，我们报告了使用廉价的左旋葡聚糖通过 Chiron 方法合成了 heavily fluorinated galactose、glucose、mannose、talose、allose、fucose 和 galacturonic acid methyl ester。单晶 X 射线衍射和 NMR 研究的结构分析证实了氟化碳水化合物类似物的有利 C 构象的保留，而对于三氟化 talose 衍生物，则观察到由于排斥 1,3-双轴向 F···F 相互作用而略微扭曲的构象。最后，多相邻氟原子的相对立体化学对亲脂性（logP）有强烈影响。
