A spiroisoxazolinoproline-based amino acid scaffold for solid phase and one-bead-one-compound library synthesis.
An efficient, multigram synthesis of a spiroisoxazolinoproline-based amino acid, 7, requiring minimal purification, delivering good cis:trans diastereoselectivity (approximately 1:4), and providing good yields is reported. Surface-bound studies of the reduction of an arylnitro group in the presence of an isoxazoline ring with tin(II) dichloride dihydrate were undertaken to confirm the stability of the isoxazoline ring. Full derivitization of this spiroisoxazolinoproline-based amino acid scaffold was performed during the synthesis of a sample library with high yields and high purity that validated the efficiency of the chemistry that was employed in resin-bound library synthesis. A 129,600 member one-bead-one-compound (OBOC) library based on the scaffold 7 was synthesized utilizing a dual amino acid encoding method and bifunctionalization of TentaGel resin.
Dixon
Seth M
SM
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, USA.
Milinkevich
Kristin A
KA
Fujii
Jeffrey
J
Liu
Ruiwu
R
Yao
Nianhuan
N
Lam
Kit S
KS
Kurth
Mark J
MJ
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis*; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013141:Spiro Compounds / Q000138:chemical synthesis*
D010080:Oxazoles; D013141:Spiro Compounds; D011392:Proline