Improved synthesis of 2'-deoxy-2'-[18F]-fluoro-1-beta-D-arabinofuranosyl-5-iodouracil ([18F]-FIAU).
An improved synthesis of 2'-[(18)F]-fluoro-2'-deoxy-1-beta-D-arabinofuranosyl-5-iodouracil ([(18)F]-FIAU) has been developed. The method utilizes trimethylsilyl trifluoromethanesulfonate (TMSOTf) catalyzed coupling of 2-deoxy-2-[(18)F]-fluoro-1,3,5-tri-O-benzoyl-d-arabinofuranose with 2,4-bis(trimethylsilyloxy)-5-iodouracil to yield the protected dibenzoyl-[(18)F]-FIAU. Dibenzoyl-[(18)F]-FIAU was deprotected with sodium methoxide to yield a mixture of alpha- and beta-anomers in a ratio of 1:1, which were purified by HPLC. The procedure described in this article eliminates the need for HBr activation of the sugar prior to coupling with silylated iodouracil and is suitable for automation. The total reaction time was about 110 min, starting from [(18)F]-fluoride. The average isolated yield of the required beta-anomer was 10+/-6% (decay corrected) with average specific activity of 125 mCi/micromol.
Anderson
Harry
H
Advion BioSystems, 19 Brown Road, Ithaca, NY 14850, USA.
Pillarsetty
Nagavarakishore
N
Cantorias
Melchor
M
Lewis
Jason S
JS
D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D005462:Fluorine Radioisotopes; D007700:Kinetics; D008698:Mesylates / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry
D005462:Fluorine Radioisotopes; D008698:Mesylates; D014297:Trimethylsilyl Compounds; C053353:trimethylsilyl trifluoromethanesulfonate; D001086:Arabinofuranosyluracil; C043457:fialuridine
Eur J Nucl Med Mol Imaging. 2007 Jun;34(6):822-9
17206416
Nucl Med Biol. 2003 Apr;30(3):215-24
12745012
J Nucl Med. 2009 Jul;50(7):1013-6
19525449
Mol Imaging Biol. 2008 Mar-Apr;10(2):82-91
18157580
Nat Rev Microbiol. 2004 Sep;2(9):704-20
15372081
J Nucl Med. 2008 Apr;49(4):637-48
18344433
Chem Pharm Bull (Tokyo). 1984 Apr;32(4):1441-50
6467456
J Nucl Med. 2008 Jul;49(7):1162-70
18552144
Nat Biotechnol. 2003 Apr;21(4):405-13
12652311
Cell Res. 2009 Mar;19(3):370-9
19114988
Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9300-5
11481488
Biochem Pharmacol. 1981 Nov 15;30(22):3071-7
6279102
Handb Exp Pharmacol. 2008;(185 Pt 2):167-223
18626603
Neoplasia. 2000 Jan-Apr;2(1-2):118-38
10933072