Research Projects

Indole is a common aromatic ring found in natural products, drugs, and medicinal compounds. Many indole-based alkaloids possess fascinating biological activities, and their direct synthesis from functionalized indoles is scarce. This proposal aims to address this issue by designing indole functional strategies to access several alkaloids, such as seven numbers of leuconolam-leuconoxine-mersicarpine triad, mucronatin A, mucronatin B, fluevirines E, norbalasubramide, balasubramide, and tryptophan derived reverse prenylated alkaloids. The reaction is designed to exploit the key feature of indole's pyrrole nucleus, which can readily undergo dearomatization and restore its aromaticity. This produces a key imine-like structure that reacts with a highly reactive yet selective nucleophile allyl boronic acid (3). The reaction occurs through a Zimmerman-Traxler-type transition state, leading to branch selective reverse allylation to produce desired products. The addition of intermediates 7 will be studied in detail to understand the reaction pathway, using experiments and DFT studies. The generation of this key quaternary center 7 in an asymmetric fashion is highly challenging and will be achieved by asymmetric catalysis using BINOL derivatives and chiral Brønsted acid catalyst. The allyl boronic acids (3) are known for their excellent functional group tolerance, allowing ample freedom to choose the allyl alcohol for total synthesis of proposed alkaloids. Selective reactions with bis-electrophiles will be used to synthesize optically pure key building blocks such as 2-amino-ketone, 2-amino alcohols, and 1,2-diamines. Successful execution of this work will lead to several key synthetic method developments, providing a novel retrosynthetic route for indole-based alkaloids.