Enantioselective Total Synthesis of (-)-Alstoscholarisine A
Enantioselective Total Synthesis of (-)-Alstoscholarisine A
复制标题
(-)-Alstoscholarisine A 的对映选择性全合成
DOI：
10.1021/jacs.6b00625
复制
发表时间：
2016-03-02
影响因子：
15
通讯作者：
Yang, Yu-Rong
中科院分区：
文献类型：
--
作者：
Liang, Xiao;Jiang, Shi-Zhi;Yang, Yu-Rong
我们报道了（-）-alstoparisine A（1）的一个简明的和高对映选择性的全合成，（-）-alstoparisine A（1）是一个最近分离的单萜吲哚生物碱，具有显著的促进成体神经干细胞增殖的生物活性。一个高度对映体选择性（99%ee），分子内Ir催化的傅-克烷基化吲哚9与仲烯丙醇被用来建立第一个立体中心后，其他三个连续的手性中心很容易设置一个高度立体选择性串联1，4-加成和羟醛缩合反应。关键的四氢吡喃是通过半缩醛还原得到的，最终的缩醛胺桥是通过一锅还原胺化/环化得到的。这种方法的简洁性是通过在每一步中用最低限度的保护基团策略建立核心键来突出的。
We report a concise and highly enantioselective total synthesis of (-)-alstoscholarisine A (1), a recently isolated monoterpenoid indole alkaloid that has significant bioactivity in promoting adult neuronal stem cells proliferation. A highly enantioselective (99% ee), intramolecular Ir-catalyzed Friedel-Crafts alkylation of indole 9 with a secondary allylic alcohol was utilized to establish the first stereogenic center upon which the other three contiguous chiral centers were readily set by a highly stereoselective tandem 1,4-addition and aldol reaction. The key tetrahydropyran was constructed through a hemiacetal reduction, and the final aminal bridge was forged by a one-pot reductive amination/cyclization. The conciseness of this approach was highlighted by building core bonds in each step with a minimalist protecting group strategy.