title: Reagent-based DOS: developing a diastereoselective methodology to access spirocyclic- and fused heterocyclic ring systems.
abstract: Herein, we report a diversity-oriented-synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N-heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N-heterocycles. The two-step sequence starts with a chiral-bicyclic-lactam-directed enolate-addition/substitution step. This step is followed by a ring-closure onto the built-in scaffold electrophile, thereby leading to stereoselective carbocycle- and spirocycle-formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug-like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell-lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry.
authors.affiliation: GVK Biosciences Pvt Ltd., Department of Medicinal Chemistry, 28 A IDA Nacharam, Hyderabad, India.
authors.forename: V Surendra Babu
authors.initials: VS
authors.lastname: Damerla
authors.forename: Chiranjeevi
authors.initials: C
authors.lastname: Tulluri
authors.forename: Rambabu
authors.initials: R
authors.lastname: Gundla
authors.forename: Lava
authors.initials: L
authors.lastname: Naviri
authors.forename: Uma
authors.initials: U
authors.lastname: Adepally
authors.forename: Pravin S
authors.initials: PS
authors.lastname: Iyer
authors.forename: Y L N
authors.initials: YL
authors.lastname: Murthy
authors.forename: Nampally
authors.initials: N
authors.lastname: Prabhakar
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Sen
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry; D008968:Molecular Conformation; D013141:Spiro Compounds / Q000737:chemistry*; D055672:Static Electricity; D013237:Stereoisomerism
chemical_list: D001643:Bridged Bicyclo Compounds; D006571:Heterocyclic Compounds; D007769:Lactams; D013141:Spiro Compounds