Abstract
A symmetrical difluorinated bilirubin analog, 8,12-bis(2-carboxy-2-fluoroethyl)-3,17-diethyl-2,7,13,18-tetramethyl-10H,21H,23H,24H-biline-1,19-dione (9), was synthesized from methyl 3-[2,4-dimethyl-5-(methoxycarbonyl)-1H-pyrrol-3-yl] propionate (1) in nine steps. Fluorine was introduced by reaction of an intermediate methyl 3-[1-(tert-butoxycarbonyl)-2,4-dimethyl-5-(methoxycarbonyl)-1H-pyrrol-3-yl]-2-hydroxypropionate (5), with (diethylamino)sulfur trifluoride (DAST). The fluorinated rubin exhibited the expected IR, UV-vis, and NMR spectroscopic properties, similar to those of the unfluorinated parent, mesobilirubin XIIIalpha. However, the solubility properties unexpectedly differed, with the fluorinated rubin being less soluble in organic solvents than its parent. While this phenomenon may be attributed to the much increased acidity of the carboxylic acid hydrogens in 9, it probably also arises from less effective intramolecular hydrogen bonding due to a decreased basicity of the propionic acid carbonyl groups.
Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
