Wang Wenbo, Wu Jiawei, Jiang Kaiyu, Zhou Maochao, He Gang
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University Tianjin 300071 China
Frontiers Science Center for New Organic Matter, Nankai University Tianjin 300071 China.
Chem Sci. 2024 Dec 2;16(1):410-417. doi: 10.1039/d4sc07410f. eCollection 2024 Dec 18.
1,2--Aryl furanosides are prevalent in nature and exhibit significant biological activities. The 1,2- configuration is less favorable in terms of stereoelectronic and steric effects, making the synthesis of this type of skeleton highly challenging. Traditional methods for the synthesis of 1,2--aryl furanosides usually require complicated protection manipulations, resulting in lengthy synthetic routes and low overall efficiency. Here, we report a simple and highly applicable procedure for the synthesis of 1,2--aryl furanosides from unprotected aldoses Petasis reaction and subsequent deaminative cyclization. Unprotected aldose mediated Petasis reactions yield linear 1,2- 1-aryl polyhydroxy amines. Halogenation of the amine motif activates the conventionally inert C-N bond and triggers the key stereoinvertive intramolecular substitution process, affording 1,2--aryl furanosides with excellent chemo- and diastereoselectivity. This procedure does not require the use of any sensitive reagents, and can be conducted in one-pot without precautions against oxygen or moisture, offering a streamlined approach to 1,2--aryl furanoside natural products and bioactive agents.
1,2-芳基呋喃糖苷在自然界中普遍存在，并表现出显著的生物活性。就立体电子效应和空间效应而言，1,2-构型不太有利，这使得这类骨架的合成极具挑战性。传统的1,2-芳基呋喃糖苷合成方法通常需要复杂的保护操作，导致合成路线冗长且整体效率低下。在此，我们报道了一种从未保护的醛糖通过Petasis反应及随后的脱氨基环化反应合成1,2-芳基呋喃糖苷的简单且高度适用的方法。未保护的醛糖介导的Petasis反应生成线性1,2-1-芳基多羟基胺。胺基序的卤化激活了传统上惰性的C-N键，并引发关键的立体反转分子内取代过程，以优异的化学和非对映选择性得到1,2-芳基呋喃糖苷。该方法无需使用任何敏感试剂，且可在无氧气或水分防护措施的情况下一锅法进行，为1,2-芳基呋喃糖苷天然产物和生物活性剂提供了一种简化的合成方法。
