Instituto de Química, Universidad Nacional Autónoma de México , Circuito Exterior s/n, Ciudad Universitaria, Coyoacán C.P. 04510, México City, México.
J Org Chem. 2017 Aug 18;82(16):8464-8475. doi: 10.1021/acs.joc.7b01211. Epub 2017 Aug 4.
A stereodivergent C-glycosidation of carbohydrate-derived lactones can be mediated by the protecting groups and applied to the total synthesis of (+)-varitriol and of two diastereoisomers thereof, which represent an unprecedent use of the protecting groups in the synthesis of a naturally occurring compound. In particular, the stereoselective nucleophile attack for 2,3-trans-substituted five-membered ring oxocarbenium ions is strongly influenced by the presence of aromatic rings in the protecting groups. According to quantum chemical calculations, the stereoselectvity depends on the π-π interactions between the aromatic ring of the C-2 protecting group with the exocyclic triple bond and the oxocarbenium ion. These interactions account for the stabilization of the conformer in which the C-2 and C-3 substituents adopt pseudoaxial orientations. When protecting groups do not contain an aromatic ring, the sterochemical outcome is dictated by stereoelectronic factors established by the Woerpel's model. Based on these findings, a concise total synthesis of the natural product (+)-varitriol and of two diastereoisomers was acomplished.
糖衍生内酯的立体发散 C-糖苷化可以通过保护基团介导，并应用于(+)-varitriol 及其两种非对映异构体的全合成，这代表了保护基团在天然产物合成中的一个前所未有的应用。特别是，对于 2,3-反式取代的五元环氧碳正离子的立体选择性亲核进攻强烈受到保护基团中芳环的存在的影响。根据量子化学计算，立体选择性取决于 C-2 保护基的芳环与环外三键和氧碳正离子之间的π-π 相互作用。这些相互作用解释了 C-2 和 C-3 取代基采用假轴向取向的构象的稳定性。当保护基团不包含芳环时，立体化学结果由 Woerpel 模型确定的立体电子因素决定。基于这些发现，完成了天然产物(+)-varitriol 及其两种非对映异构体的简洁全合成。
