title: Practical and reliable synthesis of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-beta-D-mannopyranose, a precursor of 2-deoxy-2-[18F]fluoro-D-glucose (FDG).
abstract: OBJECTIVE
  To develop a practical and reliable synthesis of 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-beta-D-mannopyranose (mannose triflate), a precursor of 2-deoxy-2-[18F]fluoro-D-glucose (FDG).
  
  
  METHODS
  The key intermediate in the preparation of the triflate precursor, 1,3,4,6-tetra-O-acetyl-beta-D-mannopyranose, was synthesized starting from D-mannose via the following four steps: (1) per-O-acetylation with Ac2O-I2, (2) formation of acetobromomannose with 30% HBr in AcOH, (3) 1,2-orthoester formation with EtOH-2,4,6-collidine and (4) hydrolysis of the 1,2-orthoester with 1M aqueous HCl. Triflation of this key intermediate with Tf2O-pyridine then completed the synthesis of the mannose triflate.
  
  
  RESULTS
  Starting from 200 g of D-mannose, the triflate precursor was synthesized with an overall yield of 65 g to 85 g (12% to 16%) in approximately seven days. The inherent low efficiency of the orthoester hydrolysis was compensated by the quantitative recovery and subsequent recycling of penta-O-acetyl-D-mannopyranose.
  
  
  CONCLUSIONS
  A large-scale preparation of mannose triflate is now routinely carried out to satisfy the growing needs for FDG in both research centers and hospitals.
authors.affiliation: Crump Institute of Molecular Imaging and LA Tech Center, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, CA 90230, USA. ttoyokuni@mednet.ucla.edu
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Toyokuni
authors.forename: J S
authors.initials: JS
authors.lastname: Dileep Kumar
authors.forename: Paula
authors.initials: P
authors.lastname: Gunawan
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Basarah
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
mesh_terms: D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives*
chemical_list: D019788:Fluorodeoxyglucose F18; D008358:Mannose