Uridine Diphosphate → 4-Oxoretinoic acid

Reaktionsgleichung

[Si](C)(C)(C)C.[CH3:6][C:7]1[CH:12]([OH:13])[CH2:11][CH2:10][C:9]([CH3:15])([CH3:14])[C:8]=1/[CH:16]=[CH:17]/[C:18](/[CH3:28])=[CH:19]/[CH:20]=[CH:21]/[C:22](/[CH3:27])=[CH:23]/[C:24]([OH:26])=[O:25].C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1>>[CH3:6][C:7]1[C:12](=[O:13])[CH2:11][CH2:10][C:9]([CH3:14])([CH3:15])[C:8]=1/[CH:16]=[CH:17]/[C:18](/[CH3:28])=[CH:19]/[CH:20]=[CH:21]/[C:22](/[CH3:27])=[CH:23]/[C:24]([OH:26])=[O:25]

Komponenten

Edukt 3

HCID 6031Uridine Diphosphate

HCID 6396Tetramethylsilane

HCID 64386294-Hydroxyretinoic acid

Produkt 1

HCID 64370634-Oxoretinoic acid

Versuchsvorschrift

Melting points (mp) are determined with a Fischer-Johns melting point apparatus and are uncorrected. Proton magnetic resonance spectra (1H NMR) are recorded in CDCl3 on a Mac NMR 5.3 300 MHz spectrometer (internal standard Me4Si, (δ=0), and high resolution mass spectra (HRMS) are determined on a Kratos Aspect Systems instrument, EI mode. Elemental analyses are performed by Chemisar Laboratories Inc., Guelph, Ontario, Canada. TLC is done on silica gel GHLF precoated plates (250 microns) purchased from Analtech, while flash column chromatography (FCC) is performed on silica gel (Merck grade 9385, 230-400 mesh, 60 Å) according to Still's method. (Still, W. C.; Kahn, M.; Mitra, A. Rapid Chromatographic Technique for Preparative Separation with Moderate Resolution. J. Org. Chem., 43, 2923-2925, 1978). “Pet. ether” refers to light petroleum, bp 40-60° C. [11,12-3H] All-trans-retinoic acid (ATRA, 51.8 (Ci/mmol) is purchased from New England Nuclear Life Science Products, Inc., while unlabeled ATRA is purchased from Sigma-Aldrich Chemical Co., St. Louis, Mo. Liarozole fumarate is obtained from Janssen Pharmaceutica, Beerse, Belgium. (±)-4-Hydroxy-ATRA and 4-oxo-ATRA are prepared using a well-known technique (Samokyszyn, V. M.; Gall, W. E.; Zawada, G.; Freyaldenhoven, M. A.; Chen, G.; Mackenzie, P. I.; Tephly, T. R.; Radominska-Pandya, A. 4-Hydroxyretinoic Acid, a Novel Substrate for Human Liver Mcrosomal UDP-glucuronosyltransferase(s) and Recombinant UGT2B7. J. Biol. Chem. 2000, 275, 6908-6914.)