Executive Summary : | Designing cascade sequences for target-oriented synthesis of complex natural products and their analogues is a significant challenge in total synthesis. C-H activation and hydroamination are crucial strategies for eco-friendly chemical synthesis, with high atom economy and reduced waste production. Understanding the cascade sequence of C(sp3)-H activation, especially C-H activation of methyl group without catalyst, followed by hydroamination reaction, can help synthesize various nitrogen-containing natural, unnatural, and complex molecules efficiently. Bisquinolines are important in medicine as they are active against TB-Drug resistant bacterial strains and Chloroquine-resistant malarial parasites. This project proposes a novel catalyst-free methodology involving a cascade sequence of C(sp3)-H activation and hydroamination for synthesizing a new class of bisquinolines and its derivatives. Preliminary studies have successfully synthesized and characterized the parent compound, but optimization and substrate scope are yet to be performed. Ultra sonication will be applied for time and energy efficiency. The target complex class of bisquinolines is analogous to the first-in-class di-aryl Quinoline compound TMC207, a potent drug for tuberculosis. They are expected to be excellent drugs against TB-Drug resistant bacterial strains and Chloroquine-resistant malarial parasites. Molecular-based nonlinear optical (NLO) materials are important for upcoming photonic and optoelectronic technologies. Bisquinolines are expected to have better NLO properties due to lower HOMO-LUMO gap energy and higher hyperpolarizability value. The success of this project will enable the application of the same principle to many other reactions, benefiting not only the research community but also the nation and humanity. |