856433-12-0Relevant academic research and scientific papers
Discovery of novel FabF ligands inspired by platensimycin by integrating structure-based design with diversity-oriented synthetic accessibility
Fisher, Martin,Basak, Ramkrishna,Kalverda, Arnout P.,Fishwick, Colin W. G.,Bruce Turnbull,Nelson, Adam
, p. 486 - 494 (2014)
An approach for designing bioactive small molecules has been developed in which de novo structure-based ligand design (SBLD) was focused on regions of chemical space accessible using a diversity-oriented synthetic approach. The approach was exploited in the design and synthesis of a focused library of platensimycin analogues in which the complex bridged ring system was replaced with a series of alternative ring systems. The affinity of the resulting compounds for the C163Q mutant of FabF was determined using a WaterLOGSY competition binding assay. Several compounds had significantly improved affinity for the protein relative to a reference ligand. The integration of synthetic accessibility with ligand design enabled focus to be placed on synthetically-accessible regions of chemical space that were relevant to the target protein under investigation.
Synthetic studies on (-)-scabronine A
Watanabe, Hideaki,Nakada, Masahisa
, p. 1518 - 1522 (2008/09/19)
This Letter describes synthetic studies on (-)-scabronine A utilizing a new chiral building block successfully prepared via the catalytic asymmetric intramolecular cyclopropanation (IMCP) of an α-diazo-β-keto sulfone. The crucial transformations in this s
Stereoselective syntheses of 4-hydroxy 4-substituted glutamic acids
Tamura, Osamu,Shiro, Tomoya,Ogasawara, Mizuho,Toyao, Atsushi,Ishibashi, Hiroyuki
, p. 4569 - 4577 (2007/10/03)
The 4-hydroxy 4-substituted glutamic acid moiety is a common substructure of biologically important natural products such as monatin [(2S,4S)-2], lycoperdic acid (3), and dysiherbaine (4). To develop methodology for syntheses of these natural products, cycloadditions of nitrone 5 with 2-substituted 2-propen-1-ols 6 and 2-substituted acrylates 8 were investigated. Reactions of nitrone 5 with alcohols 6 in the presence of MgBr2OEt2 gave cycloadducts 7 in a highly stereoselective manner, whereas noncatalyzed reactions of 5 with acrylates 8 afforded adducts 9. Using the former reaction, syntheses of monatin [(2S,4S)-2], monatin derivative 18, and lycoperdic acid (3) were accomplished. The C4-epimer of monatin [(2S,4R)-2)] was also synthesized by employing the latter cycloaddition.
