Ligand-free Suzuki-Miyaura coupling with sulfur-modified gold-supported palladium in the synthesis of a conformationally-restricted cyclopropane compound library with three-dimensional diversity.
A conformationally restricted privileged structure library with stereochemical diversity for a "fragment growth" methodology comprising 90 compounds was designed and systematically and efficiently synthesized using sulfur-modified Au-supported Pd (SAPd)-catalyzed ligand-free Suzuki-Miyaura coupling of vinyl iodide promoted by microwave and subsequent amidation in liquid-phase combinatorial chemistry as key reactions. Evaluation of the compounds with a 20-kinase panel indicated the usefulness of this "fragment growth" methodology for finding hit library compounds for fragment-based drug discovery.
Faculty of Pharmaceutical Sciences, Hokkaido University , Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Mitsuhiro
M
Arisawa
Takatoshi
T
Sato
Naoyuki
N
Hoshiya
Mohammad
M
Al-Amin
Yuji
Y
Kogami
Satoshi
S
Shuto
D020650:Combinatorial Chemistry Techniques; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry*; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000737:chemistry
D003521:Cyclopropanes; D054852:Small Molecule Libraries; D014753:Vinyl Compounds; C569210:vinyl iodide; D010165:Palladium; D013455:Sulfur; D006046:Gold; C030797:cyclopropane
Suzuki−Miyaura coupling; privileged structure library; stereochemical diversity