Two-step regio- and stereoselective syntheses of [19F]- and [18F]-2-deoxy-2-(R)-fluoro-β-D-allose

Replacement of specific hydroxyl groups by fluorine in carbohydrates is an ongoing challenge from chemical, biological, and pharmaceutical points of view. A rapid and efficient two-step, regio- and stereoselective synthesis of 2-deoxy-2-(R)-fluoro-beta-(D)-allose (2-(R)-fluoro-2-deoxy-beta-(D)-allose; 2-FD beta A), a fluorinated analogue of the rare sugar, D-allose, is described. TAG (3,4,6-tri-O-acetyl-1,5-anhydro-2-deoxy-(D)-arabino-hex-1-enitol or 3,4,6-tri-O-acetyl-(D)-glucal), was fluorinated in anhydrous HF with dilute F-2 in a Ne/He mixture or with CH3COOF at -60 degrees C. The fluorinated intermediate was hydrolyzed in 1 N HCl and the hydrolysis product was purified by liquid chromatography and characterized by 1D H-1, C-13, and F-19 NMR spectroscopy as well as 2D NMR spectroscopy and mass spectrometry. In addition, F-18-labeled 2-deoxy-2-(R)-fluoro-beta-(D)-allose (2-[F-18]FD beta A) was synthesized for the first time, with an overall decay-corrected radiochemical yield of 33 +/- 3% with respect to [F-18]F-2, the highest radiochemical yield achieved to date for electrophilic fluorination of TAG. The rapid and high radiochemical yield synthesis of 2-[F-18]FD beta A has potential as a probe for the bioactivity Of (D)-allose. (c) 2005 Elsevier Ltd. All rights reserved.