Research Projects

Sp3-Rich polycyclic scaffolds are omnipresent in biologically active alkaloids, natural products, and drugs and thus, synthetic strategies toward construction of these scaffolds are of particular importance. In addition, there is growing belief in the medicinal and biochemical communities that higher sp3 character in the molecule enhances selectivity and potency toward a bio-macromolecular target. Thus, in the current trend, synthetic and medicinal chemists tend to pay their much attention to create such sp3– rich collections of molecules and as a result, a number of efficient synthetic methods emerged for the stereo –and enantioselective synthesis of complex scaffolds. Desymmetrization of prochiral symmetric molecule is one of the powerful tool for the synthesis of novel chiral scaffolds and natural products. In the last decades, suitably substituted prochiral cyclohexa-2,5-dinones, attracted much attention to access structurally diverse sp3-rich molecules through desymmetrization strategy. Cyclohexa-2,5-dienones has multifaceted reactivity centres, which can utilized later or in the same pot after desymmetrization-step to build complexity in the product through domino process. Complexity in the products can be envisioned from the design of suitable starting materials by introducing multiple reactive points and functionalities. Various suitably substituted (alkenyl and alkynyl) symmetrical cyclohexa-2,5-dinones have been well explored through C-C bond formation reactions, whereas remarkably less reports with asymmetric desymmetrization through C-X bond formation (moreover limited to bicyclic scaffolds). In this proposal, direct asymmetric desymmetrization strategy is being proposed for the selective formation of ring-fused aminals and polycyclic amines through enantioselective C-N bonds formation. Synthesis of chiral hemi-aminal and its exploration as multitalented chiral scaffold are also proposed. As silanes are useful class of molecules, used in materials and synthetic organic chemistry, stereoselective synthesis of tetracyclic silanes is being proposed using desymmetrization strategy. Synthesis of sp3-rich polycyclic heterocycles and axially chiral pyrroles are also being proposed through desymmetrization strategy. Given the importance of exploration of sp3-rich molecules in the modern medicinal chemistry, here, we propose to explore first-in-class chemical series of polycyclic scaffolds against GPCRs, based on our initial results for selective TGR5 (EC50 366 nM) for CNS. As an expected outcome, these synthetic methods can be published in scientific publications or patented. The proposed work is important in fundamental aspects as well as in translational research in medicinal/drug discovery by creating novel chemical space and Intellectual Property (IP).