Shi Liu, Xiong Qiang, Wu Shu-Yi, Li Yang, Shen Peng, Lu Ji, Ran Guang-Yao
Department of Medicinal Chemistry, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.
College of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Org Lett. 2023 Mar 31;25(12):2030-2035. doi: 10.1021/acs.orglett.3c00374. Epub 2023 Mar 20.
Ten-membered lactones are the core units of many biologically active natural products but with a great synthetic challenge. Based on the principle of vinylogy, novel types of cyclic vinylogous anhydrides have been designed as five-carbon carbonyl synthons, further applied in [5 + 5] annulation with vinylethylene carbonates under chiral palladium catalysis. This strategy features excellent regioselectivity, mild conditions, and broad substrate scope, affording a range of spiro ten-membered lactones bearing oxindole and pyrrolidinone motif in excellent yield (up to 99%) with moderate to high enantioselectivity (up to 89% ee).
十元内酯是许多生物活性天然产物的核心单元，但合成难度很大。基于插烯原理，设计了新型环状插烯酸酐作为五碳羰基合成子，并进一步将其应用于在手性钯催化下与碳酸乙烯酯的[5 + 5]环化反应。该策略具有区域选择性优异、条件温和、底物范围广的特点，能以优异的产率（高达99%）和中等至高对映选择性（高达89% ee）得到一系列带有氧化吲哚和吡咯烷酮基序的螺十元内酯。
