Small molecules have always been the interest in chemistry and biology because of their ability to exert significant effects on the functions of macromolecules that comprise living systems. The unique structural features of spiro-oxindoles with wide range of biological activities have made them privileged structures in drug discovery. The key structural characteristics of these compounds is the spiro ring fused at the C-3 position of the oxindole. Development of suitable methodology to access structurally diverse spiro-oxindoles is formidable challenge. Till date only fewer efficient reports are known in the literature to synthesize structurally diverse spiro-oxindoles. Existing literature methodologies have limitations such as the use of metal catalysts, harsh reaction conditions and involvement of multiple steps. A general way to improve synthetic efficiency and also to access diversified molecules is through annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favourable way. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance to improve the efficiency and efficacy of the drugs. Design and development of efficient synthetic strategies to access C-3 fused carbocyclic as well as heterocyclic spiro-oxindoles has been established. An efficient methodology for the construction of highly functionalized carbocyclic spiro-oxindoles through Hauser annulation has been demonstrated. Metal free 1,6 conjugate addition induced annulation of para quinone methide to furnish pyrazolone fused spiro-oxindole derivatives and Michael addition of Morita Baylis Hillman alcohols followed by cascade cyclization to access bis spiro pyrano-pyrazolone bearing spirocyclic oxindoles have been established in our laboratory. Demonstrated green approach towards the synthesis of spirooxindole4-pyran motif with excellent yields in water as reaction medium. Therapeutic applications of the synthesized spiro-oxindole derivatives are currently in progress.

Publications:
1. Kanduru Lokesh.; Kesavan Venkitasamy., Efficient synthesis of highly functionalized Spirocarbocyclic Oxindoles via Hauser Annulation. Eur. J. Org. Chem, 2017, 37 5689-5695.

2. Pratap Reddy Gajulapalli, V.; Kanduru Lokesh.; Vishwanath, Manjunatha; Kesavan Venkitasamy; Organocatalytic construction of spirooxindole naphthoquinones through Michael/hemiketalization using L-proline derived bifunctional thiourea RSC. Adv, 2016, 6 (15), 12180-12184.

3. Nandarapu Kumarswamyreddy.; Kanduru Lokesh.; Kesavan Venkitasamy; Efficient synthesis of highly functionalized indole and phenol containing 3,3-disubstituted oxindoles and chromene fused spirooxindoles. Tetrahedron Letters 2018, 59 4344-4348.

4. V. Pratap Reddy Gajulapalli, Nandarapu Kumarswamyreddy, Kanduru Lokesh, Prof. Venkitasamy Kesavan, Enantioselective synthesis of 3-acetyl coumarin substituted 3-hydroxy oxindoles and pyranocoumarin fused spiro-oxindoles, Chemistry select 2021, 6 7855-7859.