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

Abstract

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-β- d-allose (2-( R)-fluoro-2-deoxy-β- d-allose; 2-FDβA), 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 CH 3COOF at −60 °C. The fluorinated intermediate was hydrolyzed in 1 N HCl and the hydrolysis product was purified by liquid chromatography and characterized by 1D 1H, 13C, and 19F NMR spectroscopy as well as 2D NMR spectroscopy and mass spectrometry. In addition, 18F-labeled 2-deoxy-2-( R)-fluoro-β- d-allose (2-[ 18F]FDβA) was synthesized for the first time, with an overall decay-corrected radiochemical yield of 33 ± 3% with respect to [ 18F]F 2, the highest radiochemical yield achieved to date for electrophilic fluorination of TAG. The rapid and high radiochemical yield synthesis of 2-[ 18F]FDβA has potential as a probe for the bioactivity of d-allose.