Formal synthesis of (−)-morphine from d-glucal based on the cascade Claisen rearrangement

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• 作者：Hiroki Tanimoto ; Ryosuke Saito ; Noritaka Chida
• 关键词：Morphine ; Dihydroisocodeine ; Total synthesis ; Cascade Claisen rearrangement ; Friedel– ; Crafts type cyclization
• 刊名：Tetrahedron Letters
• 出版年：2008
• 期刊代码：109_00404039
• 类别：ch
• 出版时间：7 January 2008
• 卷：49
• 期：2
• 页码：358-362
• 文件大小：166 K

摘要

The formal synthesis of (−)-morphine is described. The C-ring in morphine was prepared in an optically pure form from d-glucal using Ferrier’s carbocyclization reaction, and the vicinal tertiary and quaternary stereocenters in the C-ring were stereoselectively generated in a one-step reaction based on the cascade sequential Claisen rearrangement of an allylic vicinal diol derivative. After the one-step formation of the dibenzofuran structure, the intramolecular Friedel–Crafts type reaction effectively constructed the ABCE-phenanthrofuran skeleton. Introduction of a tosylamide function, followed by reductive cyclization furnished (−)-dihydroisocodeine, the known synthetic intermediate for (−)-morphine.