172102-39-5Relevant articles and documents
Arabinofuranose-derived positron-emission tomography radiotracers for detection of pathogenic microorganisms
Kalita, Mausam,Parker, Matthew F.L.,Luu, Justin M.,Stewart, Megan N.,Blecha, Joseph E.,VanBrocklin, Henry F.,Evans, Michael J.,Flavell, Robert R.,Rosenberg, Oren S.,Ohliger, Michael A.,Wilson, David M.
, p. 231 - 239 (2020/04/15)
PURPOSE: Detection of bacteria-specific metabolism via positron emission tomography (PET) is an emerging strategy to image human pathogens, with dramatic implications for clinical practice. In silico and in vitro screening tools have recently been applied to this problem, with several monosaccharides including l-arabinose showing rapid accumulation in Escherichia coli and other organisms. Our goal for this study was to evaluate several synthetically viable arabinofuranose-derived 18F analogs for their incorporation into pathogenic bacteria. PROCEDURES: We synthesized four radiolabeled arabinofuranose-derived sugars: 2-deoxy-2-[18F]fluoro-arabinofuranoses (d-2-18F-AF and l-2-18F-AF) and 5-deoxy-5-[18F]fluoro-arabinofuranoses (d-5-18F-AF and l-5-18F-AF). The arabinofuranoses were synthesized from 18F- via triflated, peracetylated precursors analogous to the most common radiosynthesis of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). These radiotracers were screened for their uptake into E. coli and Staphylococcus aureus. Subsequently, the sensitivity of d-2-18F-AF and l-2-18F-AF to key human pathogens was investigated in vitro. RESULTS: All 18F radiotracer targets were synthesized in high radiochemical purity. In the screening study, d-2-18F-AF and l-2-18F-AF showed greater accumulation in E. coli than in S. aureus. When evaluated in a panel of pathologic microorganisms, both d-2-18F-AF and l-2-18F-AF demonstrated sensitivity to most gram-positive and gram-negative bacteria. CONCLUSIONS: Arabinofuranose-derived 18F PET radiotracers can be synthesized with high radiochemical purity. Our study showed absence of bacterial accumulation for 5-substitued analogs, a finding that may have mechanistic implications for related tracers. Both d-2-18F-AF and l-2-18F-AF showed sensitivity to most gram-negative and gram-positive organisms. Future in vivo studies will evaluate the diagnostic accuracy of these radiotracers in animal models of infection.
Chemoenzymatic Platform for Synthesis of Chiral Organofluorines Based on Type II Aldolases
Fang, Jason,Hait, Diptarka,Head-Gordon, Martin,Chang, Michelle C. Y.
supporting information, p. 11841 - 11845 (2019/07/31)
Aldolases are C?C bond forming enzymes that have become prominent tools for sustainable synthesis of complex synthons. However, enzymatic methods of fluorine incorporation into such compounds are lacking due to the rarity of fluorine in nature. Recently, the use of fluoropyruvate as a non-native aldolase substrate has arisen as a solution. Here, we report that the type II HpcH aldolases efficiently catalyze fluoropyruvate addition to diverse aldehydes, with exclusive (3S)-selectivity at fluorine that is rationalized by DFT calculations on a mechanistic model. We also measure the kinetic parameters of aldol addition and demonstrate engineering of the hydroxyl group stereoselectivity. Our aldolase collection is then employed in the chemoenzymatic synthesis of novel fluoroacids and ester derivatives in high stereopurity (d.r. 80–98 %). The compounds made available by this method serve as precursors to fluorinated analogs of sugars, amino acids, and other valuable chiral building blocks.
Process for the preparation of 2'-halo-beta-L-arabinofuranosyl nucleosides
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, (2008/06/13)
The present invention is directed to the process for the preparation of 2′-deoxy-2′-halo-β-L-arabinofuranosyl nucleosides, and in particular, 2′-deoxy-2′-fluoro-β-L-arabinofuranosyl thymine (L-FMAU), from L-arabinose, which is commercially available and less expensive than L-ribose or L-xylose, in ten steps. All of the reagents and starting materials are inexpensive and no special equipment is required to carry out the reactions.
PROCESSES FOR PREPARING 2'-DEOXY-2'-FLUOROCOFORMYCIN AND STEREOISOMERS THEREOF
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, (2008/06/13)
2'-Deoxy-2'-fluorocoformycin and 2'-deoxy-8-epi-2'-fluorocoformycin are synthesized in this invention through a multi-stage process via 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha- and -beta-D-ribofuranosyl bromides. Further, according to this invention, 2'-deoxy-2'-epi-2'-fluorocoformycin and 2'-deoxy-8,2'-diepi-2'-fluorocoformycin are synthesized by a multi-stage process starting from 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide. These four 2'-fluoro derivatives of coformycin are novel compounds and have high enzyme-inhibitory activities against adenosine deaminase. In particular, these novel compounds are useful substances which exhibit therapeutic effects on acute lymphocytic leukemias due to their high enzyme-inhibitory activities above-mentioned. In addition, a variety of intermediates are obtained as novel compounds which are useful for the synthesis of the aforesaid novel 2'-fluoro derivatives of coformycin.
