Synthesis of 3,5-Disubstituted Isoxazoles Containing Privileged Substructures with a Diverse Display of Polar Surface Area.
We designed and synthesized the molecular framework of 3,5-disubstituted isoxazoles containing privileged substructures with various substituents which uniquely display polar surface area in a diverse manner. A library of 3,5-disubstituted isoxazoles were systematically prepared via 1,3-dipolar cycloaddition of alkynes with nitrile oxides prepared by two complementary synthetic routes; method A utilized a halogenating agent with a base and method B utilized a hypervalent iodine reagent. Through the biological evaluation of corresponding isoxazoles via three independent phenotypic assays, the different pattern of biological activities was shown according to the type of privileged substructure and substituent. These results demonstrated the significance of molecular design via introducing privileged substructures and various substituents to make a diverse arrangement of polar surface area within a similar 3-dimensional molecular framework.
['Kim|Mingi|M|', 'Hwang|Yoon Soo|YS|', 'Cho|Wansang|W|0000-0002-5262-9543', 'Park|Seung Bum|SB|0000-0003-1753-1433']
D000480:Alkynes D020650:Combinatorial Chemistry Techniques D061565:Cycloaddition Reaction D054879:Halogenation D007555:Isoxazoles D009570:Nitriles D010087:Oxides D054852:Small Molecule Libraries
3,5-disubstituted isoxazoles privileged substructure polar surface area nitrile oxide 1,3-diopolar cycloaddition