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).
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.
Toyokuni
Tatsushi
T
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
Dileep Kumar
J S
JS
Gunawan
Paula
P
Basarah
Ernest S
ES
Liu
Jie
J
Barrio
Jorge R
JR
Satyamurthy
Nagichettiar
N
D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000031:analogs & derivatives*
D019788:Fluorodeoxyglucose F18; D008358:Mannose