METHOD OF SYNTHESIS OF [2-F]-2-DEOXYGLUCOSE Russian patent published in 2001 - IPC

FIELD: medicine, pharmacy. SUBSTANCE: invention relates to radiolabeled pharmaceutical preparations for diagnostic aims and can be used in positron emission tomography. D-Mannose is added to acetic anhydride in the presence of 70% solution of perchloric acid, mixture is kept at the room temperature to yield D-mannose 1,2,3,4,6-pentaacetate. Then phosphorus tribromide is added at temperature 25 C, not above, followed by addition of water at cooling. Mixture is kept at the room temperature up to yield of alpha-acetobromo-D-mannose. To the latter acetate sodium solution is added at temperature 5 C, not above, and kept at the room temperature to yield mixture of 2,3,4,6- and 1,3,4,6-tetraacetates of D-mannopyranose. Reaction mass is poured on ice and extracted with organic solvent some times. Extract is dried, evaporated and residue is crystallized from diethyl ether. Obtained 1,3,4,6-tetra-O-acetyl-beta-D-manno-pyranose is dissolved in dry methylene chloride followed by addition of anhydrous pyridine and then trifluoromethanesulfo-acid anhydride is added at -20 C. Reaction mass is kept at the room temperature, solvent is removed and obtained 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-beta-D-manno- pyranose is crystallized. Then the latter is dissolved in acetonitrile, fluoride-18 and interphase catalysts are added at 85 C for 5 min and solvent is distilled off. To residue 1-2 M solution of hydrochloric acid is added and mixture is kept for 6-10 min at 120-130 C; or 0.2-0.5 M solution of sodium hydroxide is added and mixture is kept for 1-2 min at 20-30 C. Then water is added and obtained mass is purified by chromatography on anion-exchange, cation-exchange and reversed-phase resins to yield the end product. In the process of synthesis of D-mannose 1,2,3,4,6-pentaacetate temperature of reaction mass is maintained in the range 35-40 C and kept at 0-4 C for night. Phosphorus tribromide and water are added in the mole ratio D-mannose 1,2,3,4,6-pentaacetate : PBr₃:H₂O = 1: 2.5:13.6, respectively. At water addition temperature of reaction mass is maintained 10 C, not above. Methylene chloride is used as an organic solvent for extraction of mixture of D-mannopyranose 2,3,4,6- and 1,3,4,6-tetraacetates. Obtained extracts are evaporated to volume 125 ml. Before crystallization from diethyl ether extract is applied on chromatography column filled with neutral aluminium oxide and eluted with mixture hexane-methylene chloride by gradient elution at concentration of methylene chloride from 10% to 50%. The second fraction containing 1,3,4,6-tetra-O-acetyl-beta-D-mannopyranose is taken and solvents are evaporated under vacuum. Syrup-like residue is kept at 5-10 mm of mercury column at 35-40 C for 1.5-2 h and crystallized then from diethyl ether. After yield of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-beta-D-mannopyranose reaction mixture is subjected for flash-chromatography on silica gel. Then solvent is removed and residue is crystallized from diethyl ether. The first fraction after column chromatography and mother liquid after crystallization of D-mannopyranose tetraacetates are evaporated, combined, dissolved in methylene chloride and solvent is removed. Residue is subjected for the complete cycle of the above described chemical reactions and procedure is repeated three times, not less. 1,3,4,6-Tetra-O- -acetyl-beta-D-mannopyranose obtained in three cycles is combined and purified by crystallization from absolute ethyl alcohol. Resin AB-17 is used at the stage of purification of the end product as anion-exchange resin. EFFECT: improved quality, increased yield of product. 1 dwg, 1 ex