Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9038, United States.
Org Lett. 2020 Dec 4;22(23):9145-9150. doi: 10.1021/acs.orglett.0c02127. Epub 2020 Jul 30.
The rubellins are a family of stereochemically complex anthraquinoid heterodimers containing an unprecedented chemical scaffold. Although the rubellins have been known for over three decades, no total synthesis has been achieved since their discovery. Their topology is characterized by a 6-5-6 fused ring system, five neighboring stereocenters including a quaternary center all in a convoluted core, and an anthraquinone nucleus. The rubellin architecture has been shown to inhibit and reverse the aggregation of tau protein, a therapeutically relevant target for Alzheimer's disease. Herein, we describe the first stereoselective synthesis of a member of the family, (+)-rubellin C, in 16 steps. Strategic disconnections allow expedient construction of stereochemical and topological intricacy in a short sequence of borylative and transition metal-catalyzed steps.
Rubellins 是一类立体化学结构复杂的蒽醌杂二聚体，含有前所未有的化学支架。尽管 Rubellins 已经被发现了三十多年，但自发现以来，还没有实现它们的全合成。它们的拓扑结构的特点是具有 6-5-6 稠合环系统、包括一个季碳原子在内的五个相邻的立体中心都在一个复杂的核心中，以及一个蒽醌核。Rubellin 结构已被证明可以抑制和逆转 Tau 蛋白的聚集，Tau 蛋白是阿尔茨海默病的一个有治疗意义的靶点。在此，我们描述了该家族成员 (+)-Rubellin C 的首次立体选择性合成，共 16 步。通过战略切断，可以在硼化和过渡金属催化步骤的短序列中方便地构建立体化学和拓扑复杂性。
