[5+2]环加成:秋水仙碱的8步全合成（英文）
作者单位：Department of Chemistry South University of Science and Technology of China
会议名称：《中国化学会第30届学术年会》
会议日期：2016年
学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学]
关 键 词：Colchicine Gram-scale synthesis [5+2]Cycloaddition Highly enantioselective
摘 要：Colchicine, which is one of the most prominent tubulin-destabilizing agents ever discovered, is well known for its remarkable antimitotic activity. Although numerous strategies have been developed for the construction of the synthetically challenging ring system of colchicine, these processes are largely inefficient, making it difficult to access large enough quantities of these compounds for drug discovery. Here we describe the first highly enantioselective(≥99% ee) and highly concise gram-scale synthesis of(–)-colchicine from commercially available and inexpensive 2,3,4-trimethoxybenzaldehyde in eight steps and an overall yield of 9.0% without any protecting groups. Moreover, the first total synthesis of(+)-demecolcinone, metacolchicine and b-lumicolchicine has also been achieved. Notably, the challenging tricyclic 6-7-7 core of colchicine was efficiently introduced using an intramolecular oxidopyrylium-mediated [5+2] cycloaddition reaction. This work represents the most efficient synthesis of colchicine reported to date with the highest enantioselectivity.