Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan.
Org Biomol Chem. 2018 Dec 12;16(48):9305-9313. doi: 10.1039/c8ob02287a.
Alkaloids are a cornerstone in the development of medicinal and synthetic compounds due to their capability of specific recognition of targeted biomacromolecules, and uses in optical resolution and asymmetric reactions. To explore the untapped potential of the rigid and densely functionalized structures of alkaloids with precisely regulated configurations as optically active core scaffolds of self-assembling molecules, here we report the design, syntheses, chiroptical properties and self-assemblies of C2-symmetric alkaloidal amphiphiles with anti/syn stereochemical variations. Bispyrrolidinoindoline (BPI) was chosen as the optically active core scaffold. It was synthetically modified with hydrophobic alkyl chains and hydrophilic tetraethylene glycol tails to provide amphiphilicity. The anti/syn configurational differences in the amphiphiles significantly influenced the chiroptical, dynamic and supramolecular properties. Amphiphiles with anti-configurations responded to a solvent polarity change by altering their conformations, while the conformational changes of the syn-type amphiphiles were largely restricted. Furthermore, the anti-type amphiphile having the highest structural flexibility showed a characteristic split Cotton effect in an organic medium and formed the largest aggregates upon addition of water with a significant change in the circular dichroism (CD) profile, while amphiphiles having conformational restriction by the syn-configuration or a macrocyclic structure showed monomodal CD signals and afforded significantly smaller aggregates upon addition of water. Hence, the C2-symmetric alkaloidal BPI structure is demonstrated to be a useful core scaffold for supramolecular chemistry to design amphiphiles with controllable configurational diversity, which allows for the customization of chiroptical properties, conformational flexibility and self-assembly.
生物碱是药用和合成化合物发展的基石，因为它们能够特异性识别靶向生物大分子，并用于光学拆分和不对称反应。为了探索生物碱刚性和高密度功能化结构的未开发潜力，这些结构具有精确调节的构型，可用作自组装分子的手性核心支架，本文报道了具有反式/顺式立体化学变化的 C2 对称生物碱两亲物的设计、合成、手性光学性质和自组装。双吡咯烷吲哚啉（BPI）被选为手性活性核心支架。它通过疏水烷基链和亲水四乙二醇尾巴进行了合成修饰，以提供两亲性。两亲物的反式/顺式构型差异显著影响手性光学、动态和超分子性质。反式构型的两亲物通过改变构象来响应溶剂极性变化，而顺式构型的构象变化则受到很大限制。此外，具有最高结构灵活性的反式两亲物在有机溶剂中表现出特征性的分裂 Cotton 效应，并在加入水时形成最大的聚集体，圆二色（CD）谱发生显著变化，而顺式构型或大环结构限制构象变化的两亲物表现出单模态 CD 信号，并在加入水时形成明显较小的聚集体。因此，C2 对称生物碱 BPI 结构被证明是超分子化学设计具有可控构型多样性的两亲物的有用核心支架，可定制手性光学性质、构象灵活性和自组装。
