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Reagent‐Based DOS: Developing a Diastereoselective Methodology to Access Spirocyclic‐ and Fused Heterocyclic Ring Systems
Author(s) -
Damerla V. Surendra Babu,
Tulluri Chiranjeevi,
Gundla Rambabu,
Naviri Lava,
Adepally Uma,
Iyer Pravin S.,
Murthy Y. L. N.,
Prabhakar Nampally,
Sen Subhabrata
Publication year - 2012
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201200385
Subject(s) - combinatorial chemistry , in silico , ring (chemistry) , chemistry , stereoselectivity , reagent , cancer cell lines , bicyclic molecule , scaffold , stereochemistry , electrophile , organic chemistry , computer science , cancer cell , biology , catalysis , cancer , database , biochemistry , genetics , gene
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.