Bringmann Gerhard, Manchala Narasimhulu, Büttner Tobias, Hertlein-Amslinger Barbara, Seupel Raina
Institut für Organische Chemie, Universität Würzburg, Am Hubland, 97074, Würzburg, Germany.
Chemistry. 2016 Jul 4;22(28):9792-6. doi: 10.1002/chem.201600701. Epub 2016 Jun 6.
The first regio- and stereoselective total synthesis of the axially chiral 7,3'-coupled naphthylisoquinoline alkaloids ancistrocladidine (1) and ancistrotectorine (2) has been described. Both possess a 7,3'-coupled axis, which before now, was difficult to attain synthetically. Moreover, target 2 has a sensitive relative cis-array of the two methyl groups at C1 and C3 in the tetrahydroisoquinoline part. The key step in the chosen strategy was the construction of the biaryl axis in accordance with the "lactone method": the two molecular halves, which were activated in an "inverse-halogenated" form, were prefixed by an ester bridge, followed by intramolecular coupling, and atroposelective cleavage of the lactone auxiliary bridge delivered the desired biaryl scaffold.
已报道了轴向手性7,3'-偶联萘基异喹啉生物碱钩枝藤碱（1）和钩枝藤保护碱（2）的首例区域和立体选择性全合成。二者均具有7,3'-偶联轴，在此之前，该轴很难通过合成得到。此外，目标化合物2在四氢异喹啉部分的C1和C3位有两个甲基的相对敏感的顺式排列。所选策略的关键步骤是根据“内酯法”构建联芳基轴：以“反卤代”形式活化的两个分子片段，先用酯桥连接，然后进行分子内偶联，内酯辅助桥的对映选择性裂解得到所需的联芳基骨架。
