title: Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors.
abstract: A versatile synthetic route to prepare all four stereoisomeric 4-fluoro-glutamines was developed by exploiting a Passerini three-component reaction. The skeleton of 4-substituted glutamine derivatives was efficiently constructed. Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination, provided the desired products with high yields and excellent optical purity. The optically pure fluorine-18 labeled 4-fluoroglutamines were also successfully prepared using either a 18-crown-6/KHCO(3) or K[222]/K(2)CO(3) catalysis system. Preliminary cell uptake and inhibition studies using the 9L tumor cells and SF188(Bcl-xL) tumor cells (a glutamine addicted tumor derived from glioblastoma) provided strong evidence for their potential application in conjunction with positron emission tomography (PET) for in vivo imaging of tumors, which use glutamine as an alternative energy source.
authors.affiliation: Department of Radiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States. wenchao@mail.med.upenn.edu
authors.forename: Wenchao
authors.initials: W
authors.lastname: Qu
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Zha
authors.forename: Karl
authors.initials: K
authors.lastname: Ploessl
authors.forename: Brian P
authors.initials: BP
authors.lastname: Lieberman
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: David R
authors.initials: DR
authors.lastname: Wise
authors.forename: Craig B
authors.initials: CB
authors.lastname: Thompson
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D005973:Glutamine / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D054879:Halogenation; D006801:Humans; D007553:Isotope Labeling; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D055620:Optical Phenomena; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D005973:Glutamine