A solid phase library synthesis of hydroxyindoline-derived tricyclic derivatives by Mitsunobu approach.
Hydroxyindoline-derived scaffold, 9, was synthesized with the goal of generating a library of indoline-based natural product-like tricyclic derivatives to be utilized as small-molecule chemical probes. The tricyclic ring was obtained by a Mitsunobu reaction of the N-nosyl amino acid conjugate with the primary hydroxyl group. The solid-phase synthesis was achieved by immobilizing scaffold 9 onto the solid support giving a compound, 15. This was then subjected to a series of reactions on solid phase, including the Mitsunobu reaction, leading to the desired indoline-derived tricyclic derivative. The final product has two diversity sites: (i) amino acid as the first diversity and (ii) amidation of the secondary amine for the second diversity. These two diversity sites were utilized in the library generation by IRORI split-and-mix approach.
Arya
Prabhat
P
Chemical Biology Program, Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Drive, Ottawa, Ontario, Canada, K1A 0R6.
Wei
Chang-Qing
CQ
Barnes
Michael L
ML
Daroszewska
Malgosia
M
D017665:Hydroxyl Radical; D007202:Indicators and Reagents; D007211:Indoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000138:chemical synthesis*; D012996:Solutions; D012997:Solvents; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007211:Indoles; D010879:Piperazines; D011083:Polycyclic Compounds; D012996:Solutions; D012997:Solvents; D017665:Hydroxyl Radical