Executive Summary : | Environmental pollution and global regulations on manufacturing have focused to use non-hazardous feedstock chemicals and more selective and efficient chemical processes for the healthcare and related products. Subsequently, the risk and the waste produced in the chemical process can be controlled. Recent decades, integration of flow chemistry for the chemical synthesis can afford not only more selective and efficient process, it is also increased the safety, faster production and energy efficiency. In this aspiration, borrowing alkylation strategy is promising concept towards sustainability and the green chemistry goal, since it is catalytic and atom economical reactions, in which many reactions occur in one pot with the liberation of water or molecular Hydrogen as byproduct. Although, in the last two decades borrowing hydrogen concept addressed from the fundamental level studies, environmentally benign, chemoselective and scalable method is always challenge in this field. Moreover, selective cross-coupling reaction in borrowing alkylation strategy is still to be studied and much explored in this area. For example, cross-coupling of two different amino alcohols to get selective asymmetrically substituted heterocycles such as pyrazine, piperazine, dipeptide and quinazolinone derivatives have not been studied. Moreover, application of this concept toward the synthesis biologically important natural products (alkaloids, terpenes, steroids, etc) and pharmaceutical drugs especially in the field of alkaloids were not studied globally. Besides, the scalability of the product in the borrowing alkylation is limited to mg scale and upraising the scale is another challenges in this field. Therefore, primary aim of this proposal is to develop continuous flow metal-catalyzed synthesis of the various biologically important heterocycles and alkaloids using inter and intramolecular dehydrogenative coupling of alcohols and amines. To this direction, we propose to study various homogeneous and heterogeneous catalytic system for the cross-coupling reactions of amino alcohols via N-alkylation under batch and continuous flow condition. Furthermore, this strategy is also proposed for the construction of various quinazoline and quinazolinone derivatives in one pot condition under batch and continuous flow mode. Further application will be extended for the total synthesis of quinazolinone alkaloids (Asperlicin C, Rutaecarpine and Hunanmycin A). This proposal is also plan to extend the scope for the Hunanamycin A and related derivatives that has the potential to treat major infectious diseases such as tuberculosis as well as diseases caused by gram negative bacteria. The antibiotic activities of synthesized quinazolinone and quinazoline derivatives will be studied in details with the help of external collaboration. |