134653-77-3Relevant academic research and scientific papers
Systematic Diversity-Oriented Synthesis of Reduced Flavones from γ-Pyrones to Probe Biological Performance Diversity
Gerlach, Erica M.,Korkmaz, Melissa A.,Pavlinov, Ivan,Gao, Qiwen,Aldrich, Leslie N.
, p. 1536 - 1545 (2019/07/04)
Diversity-oriented synthesis (DOS) has historically focused on the development of small-molecule collections with considerable chemical diversity with the hypothesis that chemical diversity will lead to diverse biological activities. We took a systematic approach to DOS to develop a focused library of reduced flavones from ?-pyrones with diversity of appendage, stereochemistry, and chemical properties to determine which features of small molecules are most predictive of biological performance diversity. The effects of these systematic modifications on biodiversity were determined using Cell Painting and cytotoxicity assays to compare the results of multiple methods of assessment. We observed that a greater fraction of sp3 hybridized atoms (fsp3) does not always lead to enhanced biodiversity, that stereochemistry and appendage diversity both contribute to biodiversity, and that lipophilicity of the pyrone class of compounds correlates with biodiversity. These results will contribute to the development of a general algorithm to predict which chemical features should be considered during the synthesis of DOS libraries to create biological performance-diverse collections of small molecules for probe and drug discovery.
Generation and in Situ Acylation of Enaminone Anions: A Convenient Synthesis of 3-Carbethoxy-4(1H)-pyridinones and -4-pyrones and Related Compounds
McCombie, Stuart W.,Metz, William A.,Nazareno, Dennis,Shankar, Bandarpalle B.,Tagat, Jayaram
, p. 4963 - 4967 (2007/10/02)
Treatment of 2--3-oxobutanoates 9 or 10 with LiN(SiMe3)2 in the presence of RCOCl results in C-acylation.The resulting intermediate, without isolation, may be converted to 6-R 3-Carbethoxy-4-pyrones (e.g., 12) by H3O+ or to the corresponding pyridinones (e.g., 13) by NH4OAc.Typically, yields are 55-75percent for R groups lacking acidic α or γ protons and ca. 30percent for R = Me2CH or MeCH=CH.Replacing 9 with MeCOC(=CHNMe2)SCH2Ph (from MeCOCH2SCH2Ph and Me2NCH(OMe)2 similarly affords 3-(PhCH2S)-substituted products such as 29.Alkylation of the pyridinone anions produces mixtures of N- and O-substituted compounds, with the latter predominating; aminolysis of the isolated pyrones (R'NH2-HOAc, where R' = alkyl, Ar, HO, etc.) is the preferred route to the 1-R'-substituted pyridinones.
