School of Chemical Sciences , University of Auckland , Auckland 1010 , New Zealand.
J Org Chem. 2019 May 3;84(9):5747-5756. doi: 10.1021/acs.joc.9b00653. Epub 2019 Apr 18.
Aristolactams are an important subgroup of aporphinoids, which all share a common phenanthrene chromophore motif that is thought to be responsible for the range of interesting physicochemical and biological properties exhibited by these compounds. Among all of the aristolactams discovered, (+)-aristolactam GI displays a unique structural feature of having the aristolactam scaffold linked via a benzodioxane ring to a phenyl propanoid unit, resulting in the compound being an aporphinoid-lignan hybrid. The synthesis of (+)-aristolactam GI was achieved first by synthesis of an orthogonally protected aristolactam, which was prepared using a Suzuki/aldol cascade to convert a differentially protected isoindolin-1-one to the required phenanthrene. The required enantiopure phenyl propanoid unit was prepared from readily available ( R)-methyl lactate. A selective Mitsunobu reaction was used to combine these two key fragments, prior to the formation of the linking benzodioxane in the final step. The absolute stereochemistry of the natural product was confirmed to be 7' S, 8' S.
阿朴啡类生物碱是一个重要的生物碱亚组，它们都具有一个共同的菲核发色团，这被认为是这些化合物表现出的一系列有趣的物理化学和生物性质的原因。在所有已发现的阿朴啡类生物碱中，（+）-阿朴啡类生物碱 GI 具有独特的结构特征，即阿朴啡骨架通过苯并二氧杂环戊烷环与苯丙素单元相连，导致该化合物成为阿朴啡类-木脂素的杂种。（+）-阿朴啡类生物碱 GI 的合成首先通过合成正交保护的阿朴啡类生物碱来实现，该化合物是通过铃木/羟醛缩合反应将差异保护的异吲哚-1-酮转化为所需的菲来制备的。所需的对映体纯苯丙素单元是由易得的（R）-乳酸甲酯制备的。在最后一步形成连接苯并二氧杂环戊烷之前，使用选择性 Mitsunobu 反应将这两个关键片段结合在一起。天然产物的绝对立体化学被确认为 7'S，8'S。
