Institute of Organic Chemistry, University of Würzburg, Am Hubland, D-97074 Würzburg, Germany.
J Am Chem Soc. 2010 Jan 27;132(3):1151-8. doi: 10.1021/ja9097687.
The N,C-coupled naphthyldihydroisoquinoline alkaloids ancistrocladinium A (3) and B (4), which possess an unprecedented iminium-aryl axis and show high in vitro antileishmanial activities, have been synthesized via a short sequence of eight linear steps, without the need of protecting groups. Key steps were a Buchwald-Hartwig amination and a Bischler-Napieralski cyclization, preferentially leading to the naturally predominant M-atropo-diastereomer in the case of 3, while the N,C-axis is configurationally semistable in 4. The highly convergent first access to this type of alkaloids will now facilitate the preparation of structural analogues for structure-activity relationship studies. Its general applicability was shown by the preparation of the sterically even more congested, as yet unnatural N,3'- and N,1'-coupled analogues, ancistrocladinium C (5) and D (6).
具有前所未有的亚胺-芳基轴且表现出高体外抗利什曼原虫活性的 N,C-偶联萘并二氢异喹啉生物碱Ancistrocladinium A（3）和 B（4）已通过没有保护基的八个线性步骤的短序列合成。关键步骤是 Buchwald-Hartwig 胺化和 Bischler-Napieralski 环化，在 3 的情况下优先导致天然占主导地位的 M-高对映体，而 N,C-轴在 4 中构型半稳定。这种类型的生物碱的高度收敛的首次进入现在将促进结构类似物的制备，以进行构效关系研究。通过制备结构上甚至更拥挤的、迄今非天然的 N,3'-和 N,1'-偶联类似物 Ancistrocladinium C（5）和 D（6），证明了其普遍适用性。
