Synthesis of 6′-deoxy-6′-fluorosucrose

Article abstract of DOI:10.1016/j.carres.2012.12.001

A facile synthesis of 6′-deoxy-6′-fluorosucrose has been developed. The title compound is available in six linear steps in 44% overall yield from commercially available sucrose. The synthesis involves rapid and convenient fluorination and deprotection con

Full text of DOI:10.1016/j.carres.2012.12.001

Carbohydrate Research 369 (2013) 38–41
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of 60-deoxy-60-fluorosucrose
⇑
Vikram Gaddam, Michael Harmata
Department of Chemistry, University of Missouri–Columbia, Columbia, MO 65211, United States
a r t i c l e i n f o
a b s t r a c t
A facile synthesis of 60-deoxy-60-fluorosucrose has been developed. The title compound is available in six
linear steps in 44% overall yield from commercially available sucrose. The synthesis involves rapid and
convenient fluorination and deprotection conditions. This procedure would be very useful for the
incorporation of radioactive [18F].
Article history:
Received 7 November 2012
Received in revised form 30 November 2012
Accepted 1 December 2012
Available online 14 December 2012
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Fluorination
Fluorosucrose
Fluorosugar
Kryptofix [2.2.2]
1. Introduction
in positron emission tomography (PET) imaging in a clinical
setting.5
Fluorine-containing organic compounds have received much
attention because of their pharmaceutical properties.1 The synthe-
sis of targets containing fluorine and the development of methods
for the incorporation of fluorine into organic molecules have been
and remain of intense interest.2
Sucrose is one of the main dietary sugars and is consequently
the starting point for many biochemical processes. This disaccha-
ride is also the primary vehicle by which carbon transport occurs
in higher plants and serves as a signaling molecule, regulating gene
expression and consequently plant development.3
Fluorinated sucrose derivatives offer opportunities for applica-
tions in potentially many areas of biology. The fluorinated deriva-
tives that have been prepared include 3-deoxy-3-fluorosucrose,6 4-
deoxy-4-fluorosucrose,7 6-deoxy-6-fluorosucrose,8 10-deoxy-10-
fluorosucrose,9 40-deoxy-40-fluorosucrose,10 60-deoxy-60-fluorosu-
crose,10 and 6,60-dideoxy-6,60-difluorosucrose.9,11
60-Deoxy-60-fluorosucrose10 was prepared from the correspond-
ing 6-deoxy-6-fluorofructose and UDP-glucose by using chemoen-
zymatic methods involving glucose isomerase and sucrose
synthetase. To the best of our knowledge, there has been no purely
synthetic approach reported for the synthesis of 60-deoxy-60-fluo-
rosucrose. We set out to accomplish a synthesis of 60-deoxy-60-flu-
orosucrose that would be efficient, rapid, and amenable to
application in the area of positron emission tomography (PET).12
Our successful approach is detailed below.
Sucrose derivatives labeled in some fashion have been of inter-
est for monitoring sucrose metabolism, especially transport in
higher plants.4 These derivatives can be isotopically or radiochem-
ically labeled for easy detection.
Fluorinated sucrose derivatives and fluorinated carbohydrates
in general have been of interest for some time. Fluorinated carbo-
hydrates are important in understanding the role of carbohydrate
metabolism in both plants and animals. Generally, a fluorinated
carbohydrate is prepared by replacement of one of the hydroxyl
groups on the carbohydrate with a fluorine atom. Such a substitu-
tion removes the possibility of that position serving as a hydrogen-
bond donor, but not as a hydrogen bond acceptor. Hence, biochem-
ical differences may exist in the behavior of the fluorinated vis-à-
vis a native carbohydrate.
2. Results and discussion
Our synthetic approach began with commercially available su-
crose (1). The selective protection of the hydroxyl function of the
60 position of 1 with tert-butyldiphenylsilyl (TBDPS),13 was fol-
lowed by the benzoylation of remaining hydroxyl groups with ben-
zoyl chloride in pyridine, affording 60-O-tert-butyldiphenylsilyl-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose (2) in 65% overall yield
(Scheme 1). Selective deprotection of the silyl ether to yield the
alcohol, 2,3,4,6,10,30,40-hepta-O-benzoylsucrose (3), was achieved
by using 1% bromine in methanol in good yield (86%) without
migration of any of the benzoyl groups.14 For the conversion of
the alcohol to its corresponding triflate, we examined different
bases including NEt3, DIPEA, pyridine, and 2,6-lutidine along with
Perhaps the best known example of the utility of a fluorosugar
is 18F-2-deoxy-2-fluoroglucose, which finds important applications
⇑
Corresponding author. Tel.: +1 573 882 1097; fax: +1 573 882 2754.
E-mail address: harmatam@missouri.edu (M. Harmata).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.12.001

V. Gaddam, M. Harmata / Carbohydrate Research 369 (2013) 38–41
39
Scheme 1. Synthesis of sucrose-60-triflate.
triflic anhydride under different reaction conditions. The latter
base proved to be the most effective in terms of yield. Ultimately,
we
obtained
the
triflate,
60-O-trifluoromethanesulfonyl-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose (4), in excellent yield
(94%) by treating the alcohol (3) with 1.5 equiv of Tf2O and 2,6-lu-
tidine at ꢀ78 °C in dichloromethane (DCM).
The typical procedure for the fluorination of aliphatic halides
and triflates is by nucleophilic displacement with fluoride ion.15 Al-
kali metal fluorides like KF and CsF are common reagents for this
reaction. However, the poor solubility in organic solvents of KF in
particular and low nucleophilicity of fluoride generally require
harsh reaction conditions for successful substitution. To increase
the nucleophilicity and solubility of metal fluorides, the use of
crown ether derivatives such as 18-crown-6 and Kryptofix [2.2.2]
has been reported.16
Scheme 2. Synthesis of 60-deoxy-60-fluorosucrose.
complex was finished within 10 min at reflux temperature giving
(5) in excellent yield (92%, entry 3). We also carried out the fluori-
nation with TBAF and obtained 70% yield of (5) after 30 min reflux
(entry 2). Entry 4 of Table 1 shows that the use of silver fluoride
(AgF) afforded the desired product in 92% yield in 10 min without
any byproducts. We also examined the fluorination with CsF (entry
5), which proceeded smoothly and provided the corresponding
fluoride product in 96% yield. The many options for successful fluo-
rination are encouraging with respect to planned future applica-
tions of this procedure.
In the final step of the process, deprotection of benzoyl groups
on 60-deoxy-60-fluoro-2,3,4,6,10,30,40-hepta-O-benzoylsucrose (5)
by using K2CO3 in methanol at reflux temperature for 5 min pro-
vided the 60-deoxy-60-fluorosucrose (6) in 92% yield (Scheme 2).
The complete deprotection occurred within 5 min as evidenced
by crude 19F NMR, which showed a single peak at ꢀ227.1 ppm.
The product was purified by reverse phase silica gel column chro-
matography with 1% H2O/CH3CN. The deprotection reaction was
also successful using NaOMe/MeOH at reflux temperature for
5 min (80% yield). We have also developed a one-pot fluorination
and deprotection reaction and obtained 6 in 84% overall yield.
Table 1 demonstrates the nucleophilic fluorination of 60-O-tri-
fluoromethanesulfonyl-2,3,4,6,10,30,40-hepta-O-benzoylsucrose (4)
with various metal fluorides and tetrabutylammonium fluoride
(TBAF) as fluoride sources in acetonitrile at reflux temperature.
Fluorination of triflate (4) with KF in the presence of 18-crown-6
occurred after 12 h reflux in acetonitrile, affording 60-deoxy-60-flu-
oro-2,3,4,6,10,30,40-hepta-O-benzoylsucrose (5) (Table 1, entry 1) in
39% yield. The product (5) clearly showed the absence of OTf peak
13
at 120 ppm in the C NMR spectrum. In (5), C-60 is shifted to
downfield to 81.9 ppm, where it appears as a doublet due to
splitting by the a-fluorine atom (JC–F = 173.6 Hz). In addition, both
C-40 and C-50 are coupled with F-60, d 75.2 (JC–F = 6.3 Hz) and d 80.3
(JC–F = 20.0 Hz), respectively. The 19F NMR spectrum shows a dou-
blet of triplets that are centered at ꢀ229.1 ppm, due to signals aris-
ing from the fluorine atom on C-60 coupled to the two hydrogen
atoms on C-60. The same reaction with the KF/Kryptofix [2.2.2]
3. Conclusion
Table 1
Fluorination of triflate (4) with various fluoride sources in acetonitrile
In summary, we have described a novel and practical method
for the synthesis of 60-deoxy-60-fluorosucrose (6). This procedure
has the advantages of high yield and short reaction times for the
final two steps. Applications of this fluorination method to [18F]
labeling for diagnostic agents are also under investigation.
4. Experimental section
4.1. General methods
Entry
Reagent
Time
Yield (%)
1
2
3
4
5
KF/18-crown-6
TBAF
KF/Kryptofix 222
AgF
CsF
12 h
39
70
92
92
96
30 min
10 min
10 min
10 min
All reactions were carried out in oven-dried or flame-dried flasks
under an atmosphere of argon. Acetonitrile, dichloromethane, and
methanol were freshly distilled over calcium hydride. Analytical

40
V. Gaddam, M. Harmata / Carbohydrate Research 369 (2013) 38–41
thin layer chromatography was performed on normal and reverse
phase silica gel plates impregnated with a UV indicator. Flash chro-
matography was carried out using 230–400 mesh silica gel with
HPLC grade solvents. 1H and 13C NMR spectra were recorded on a
Bruker ARX-250 (250 MHz), DRX-300 (300 MHz), and DRX-500
(500 MHz) spectrometer in CDCl3 (TMS as internal standard) and
D2O. 19F NMR was recorded on a Bruker ARX-250 (250 MHz)
spectrometer in D2O (CFCl3 as external standard). Melting points
were determined with a Fisher-Johns melting point apparatus.
Infrared spectra were recorded on a Perkin Elmer 1600 series FT-
IR spectrometer. High-resolution mass spectra were performed by
College of Science Major Instrumentation Center, Old Dominion
University, with a Bruker 12 Tesla APEX–Qe FTICR-MS. Optical rota-
tions were measured with a JASCD DIP-370 digital polarimeter.
J = 6.0 Hz), 5.76 (1H, t, J = 10.0 Hz), 5.42 (1H, dd, J = 10.5, 3.5 Hz),
4.58–4.86 (5H, m), 4.33–4.44 (3H, m); 13C NMR (125 M Hz, CDCl3)
d: 166.1, 165.8, 165.5, 165.5, 165.4, 165.3, 165.1, 133.7, 133.6,
133.3, 133.2, 133.1, 133.0, 133.0, 130.2 (2C), 129.9 (4C), 129.9
(2C), 129.8 (2C), 129.7 (2C), 129.7, 129.6 (2C), 129.2 (2C), 128.9,
128.8, 128.8 (2C), 128.6, 128.6 (3C), 128.3 (4C), 128.3 (2C), 128.3
(2C), 128.2 (2C), 104.6, 91.1, 81.9 (d, J = 173.6 Hz, C-60), 80.3 (d,
J = 20.0 Hz, C-50), 75.2 (d, J = 6.3 Hz, C-40), 71.5, 70.1, 69.1, 69.0
(2C), 64.7, 62.4; 19F NMR (235 MHz, CDCl3) d: ꢀ229.1 (dt,
J = 23.5, 47.0 Hz); HRMS m/z Calcd for (C61H49FO17
)
Na+ is
1095.2845, found 1095.2819.
4.4. Fluorination procedure with KF/18-crown-6
A solution of 60-O-trifluoromethanesulfonyl-2,3,4,6,10,30,40-hep-
ta-O-benzoylsucrose (50 mg, 0.0415 mmol), 18-crown-6
4.2. 60-O-Trifluoromethanesulfonyl-2,3,4,6,10,30,40-hepta-O-
4
benzoylsucrose (4)
(219 mg, 0.083 mmol), and KF (4.8 mg, 0.083 mmol) in MeCN
(0.83 mL, 0.05 M) was vigorously refluxed under argon for 12 h.
The reaction was cooled and concentrated in vacuo. The crude
product was dissolved in CH2Cl2 (5 mL), washed with water
(3 ꢁ 5 mL) and the combined aqueous phases were extracted with
CH2Cl2 (2 ꢁ 5 mL). The combined organic phases were washed
with water (5 mL) and brine (5 mL), dried over anhydrous Na2SO4
and concentrated in vacuo. The crude product was purified by flash
silica column chromatography with 20% EtOAc/hexanes to afford
17 mg (39% yield) of the product, 60-deoxy-60-fluoro-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose (5) as a white solid.
To a stirred solution of 2,3,4,6,10,30,40-hepta-O-benzoylsucrose 3
(1.5 g, 1.40 mmol) in dry CH2Cl2 (28 mL, 0.05 M) under argon was
added 2,6-lutidine (0.244 mL, 2.1 mmol) dropwise at ꢀ78 °C. After
10 min, trifluoromethanesulfonic anhydride (0.354 mL, 2.1 mmol)
was added dropwise and stirring was continued for another 2 h.
The reaction mixture was quenched with water (1 mL) at ꢀ78 °C
and slowly warmed to room temperature. Then the CH2Cl2 layer
was washed with water (3 ꢁ 30 mL), dried over anhydrous Na2SO4
and concentrated in vacuo. The crude product was purified by flash
silica column chromatography with 20% EtOAc/hexanes to afford
1.58 g (94% yield) of the product, 60-O-trifluoromethanesulfonyl-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose (4) as a white solid. 1H
NMR (500 MHz, CDCl3) d: 8.12 (2H, t, J = 7.0 Hz), 7.96–8.01 (6H,
m), 7.88 (2H, t, J = 7.5 Hz), 7.83 (2H, t, J = 7.0 Hz), 7.79 (2H, t,
J = 7.0 Hz), 7.55–7.60 (2H, m), 7.45–7.52 (7H, m), 7.25–7.44 (10H,
m), 7.14 (2H, t, J = 8.0 Hz), 6.25 (1H, t, J = 10.5 Hz), 6.10 (1H, d,
J = 3.5 Hz), 6.05 (1H, d, J = 5.5 Hz), 5.76 (1H, t, J = 10.0 Hz), 5.70
(1H, t, J = 6.5 Hz), 5.47 (1H, dd, J = 10.5, 3.5 Hz), 5.11 (1H, dd,
J = 11.0, 7.0 Hz), 4.90 (1H, dd, J = 11.0, 2.5 Hz), 4.77–4.79 (1H, m),
4.66 (1H, d, J = 12.0 Hz), 4.54–4.59 (2H, m), 4.51–4.78 (1H, m),
4.43 (1H, dd, J = 12.5, 3.5 Hz); 13C NMR (125 MHz, CDCl3) d:
166.0, 165.7 (2C), 165.5, 165.4, 165.2, 165.1, 133.9, 133.7, 133.4,
133.3, 133.3, 133.1, 133.0, 130.1 (2C), 130.0 (2C), 129.9 (2C),
129.9 (2C), 129.8 (4C), 129.6 (2C), 129.5, 129.1, 129.0, 128.8,
128.7 (2C), 128.6 (2C), 128.5, 128.4, 128.3 (2C), 128.3 (2C), 128.3
(4C), 128.2 (2C), 128.1, 118.6 (q, J = 319.9 Hz) (CF3), 104.7, 91.1,
79.1, 76.6, 75.8, 75.4, 71.1, 69.9, 69.2, 69.1, 64.0, 62.5; HRMS m/z
Calcd for (C62H49F3O20S) Na+ is 1225.2382, found 1225.2390.
4.5. Fluorination procedure with TBAF, AgF, and CsF
A solution of 60-O-trifluoromethanesulfonyl-2,3,4,6,10,30,40-hep-
ta-O-benzoylsucrose
4
(1.0 equiv) and fluorinating agent
(1.0 equiv) in MeCN (0.05 M) was vigorously refluxed, under argon
for the appropriate time. The reaction was cooled and concentrated
in vacuo. The crude product was dissolved in CH2Cl2 (5 mL),
washed with water (3 ꢁ 5 mL) and the combined aqueous phases
were extracted with CH2Cl2 (2 ꢁ 5 mL). The combined organic
phases were washed with water (5 mL), brine (5 mL), dried over
anhydrous Na2SO4 and concentrated in vacuo. The crude product
was purified by flash silica column chromatography with 20%
EtOAc/hexanes to afford the product, 60-deoxy-60-fluoro-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose (5) as a white solid.
4.6. 60-Deoxy-60-fluorosucrose (6)
A solution of 60-deoxy-60-fluoro-2,3,4,6,10,30,40-hepta-O-benzo-
ylsucrose
5
(100 mg, 0.0931 mmol) and K2CO3 (13.0 mg,
4.3. 60-Deoxy-60-fluoro-2,3,4,6,10,30,40-hepta-O-benzoylsucrose (5)
0.0931 mmol) in methanol (1.8 mL, 0.05 M) was refluxed for
5 min. The solvent was removed and the crude product was puri-
fied by reverse phase silica column chromatography with 1%
H2O/CH3CN to give 29 mg (92% yield) of the product, 60-deoxy-60-
fluorosucrose (6). 1H NMR (500 MHz, D2O) d: 5.39 (1H, d,
J = 4.0 Hz)), 4.71–4.77 (1H, m), 4.62–4.69 (1H, m), 4.25 (1H, d,
J = 8.5 Hz), 4.16 (1H, t, J = 8.5 Hz), 4.03–4.10 (1H, m), 3.83–3.87
(1H, m) 3.78 (1H, dd, J = 4.5, 10.0 Hz), 3.75 (1H, d, J = 9.5 Hz),
3.72 (2H, s), 3.55 (1H, dd, J = 4.0, 10.0 Hz), 3.45 (1H, t, J = 9.5 Hz);
13C NMR (125 MHz, D2O) d: 103.8, 92.2, 83.2 (d, J = 166.3 Hz, C-
60), 79.3 (d, J = 18.8 Hz, C-50), 76.1 (d, J = 2.5 Hz, C-30), 72.5 (d,
J = 8.7 Hz, C-40), 72.4, 72.3, 71.0, 69.2, 60.9, 60.8; 19F NMR
(235 MHz, D2O) d: ꢀ227.1 (dt, J = 21.1, 47.0 Hz). HRMS m/z Calcd
for (C12H21FO10) Na+ is 367.1011, found 367.1008.
A solution of 60-O-trifluoromethanesulfonyl-2,3,4,6,10,30,40-hep-
ta-O-benzoylsucrose
4 (50 mg, 0.0415 mmol), Kryptofix 222
(15.6 mg, 0.0415 mmol), and KF (2.4 mg, 0.0415 mmol) in MeCN
(0.83 mL, 0.05 M) was vigorously refluxed under argon for
10 min. The reaction was cooled and concentrated in vacuo. The
crude product was dissolved in CH2Cl2 (5 mL), washed with water
(3 ꢁ 5 mL) and the combined aqueous phases were extracted with
CH2Cl2 (2 ꢁ 5 mL). The combined organic phases were washed
with water (5 mL) and brine (5 mL), dried over anhydrous Na2SO4
and concentrated in vacuo. The crude product was purified by flash
silica column chromatography with 20% EtOAc/hexanes to give
41 mg (92% yield) of the product, 60-deoxy-60-fluoro-
2,3,4,6,10,30,40-hepta-O-benzoylsucrose as a white solid. 1H NMR
(500 MHz, CDCl3) d: 8.15 (2H, d, J = 7.5 Hz)), 7.97–8.04 (6H, m),
7.79–7.85 (6H, m), 7.58 (1H, t, J = 10.0 Hz), 7.32–7.57 (14H, m),
7.25–7.30 (4H, m), 7.12 (2H, t, J = 8.0 Hz), 6.21 (1H, t, J = 10.5 Hz),
6.12 (1H, d, J = 3.5 Hz), 6.02 (1H, d, J = 6.0 Hz), 5.90 (1H, t,
4.7. One pot synthesis of 60-deoxy-60-fluorosucrose (6)
A solution of 60-O-trifluoromethanesulfonyl-2,3,4,6,10,30,40-hep-
ta-O-benzoylsucrose
4 (50 mg, 0.0415 mmol), Kryptofix 222

V. Gaddam, M. Harmata / Carbohydrate Research 369 (2013) 38–41
41
2. (a) Xu, T.; Liu, G. Synlett 2012, 23, 955–958; (b) Braun, T. Organometallics 2012,
31, 1213–1215; (c) Sato, K.; Tarui, A.; Omote, M.; Ando, A.; Kumadaki, I.
Synthesis 2010, 1865–1882; (d) Lectard, S.; Hamashima, Y.; Sodeoka, M. Adv.
Synth. Catal. 2010, 352, 2708–2732; (e) O’Hagan, D. Chem. Soc. Rev. 2008, 37,
308–319.
3. (a) Maheshwari, R.; Veluthambi, K. Curr. Sci. 2011, 101, 189–193; (b) Liesche, J.;
Kruegel, U.; He, H.; Chincinska, I.; Hackel, A.; Kuehn, C. J. Plant Physiol. 2011,
168, 1426–1433; (c) Geiger, D. Mol. Plant 2011, 4, 395–406; (d) Wind, J.;
Smeekens, S.; Hanson, J. Phytochemistry 2010, 71, 1610–1614; (e) Kuehn, C.;
Grof, C. P. L. Curr. Opin. Plant Biol. 2010, 13, 288–298.
4. (a) Henry, C.; Rabot, A.; Laloi, M.; Mortreau, E.; Sigogne, M.; Leduc, N.; Lemoine,
R.; Sakr, S.; Vian, A.; Pelleschi-Travier, S. Plant Cell Environ. 2011, 34, 1776–
1789; (b) Birschwilks, M.; Haupt, S.; Hofius, D.; Neumann, N. J. Exp. Bot. 2006,
57, 911–921; (c) Rice, A.; Liu, Y.; Michaelis, M. L.; Himes, R. H.; Georg, G. I.;
Audus, K. L. J. Med. Chem. 2005, 48, 832–838.
(15.6 mg, 0.0415 mmol), and KF (2.4 mg, 0.0415 mmol) in MeCN
(0.83 mL, 0.05 M) was vigorously refluxed, under argon for
10 min. After cooling, K2CO3 (5.7 mg, 0.0415 mmol) and methanol
(0.2 mL) were added and reflux was continued for another 5 min.
The solvent was removed and the crude product was purified by
reverse phase silica column chromatography with 1% H2O/CH3CN
affording 13 mg (84% yield) of the product, 60-deoxy-60-fluorosu-
crose 6.
Acknowledgment
This work was generously supported by a Grant from the
Department of Energy (DE-SC0002040).
5. (a) Alauddin, M. M. Am. J. Nucl. Med. Mol. Imaging 2012, 2, 55–76; (b) Smyth, E.
C.; Shah, M. A. World J. Gastroenterol. 2011, 17, 5059–5074; (c) Hashefi, M.;
Curiel, R. Ann. N.Y. Acad. Sci. 2011, 1228, 167–174; (c) Bleeker-Rovers, C. P.; Vos,
F. J.; Van, d. G. W. T. A.; Oyen, W. J. G. Oncologist 2011, 16, 980–991.
6. Binder, T. P.; Robyt, J. F. Carbohydr. Res. 1986, 147, 149–154.
7. Simiand, C.; Driguez, H. J. Carbohydr. Chem. 1995, 14, 977–983.
8. (a) Robyt, J. F.; Zikopoulos, J. N. U.S. Patent 4,228,150, 1980.; (b) Hough, L.;
Kabir, A. K. M. S.; Richardson, A. C. Carbohydr. Res. 1984, 125, 247–252; (c)
Eklund, S. H.; Robyt, J. F. Carbohydr. Res. 1988, 177, 253–258.
9. Card, P. J.; Hitz, W. D. J. Am. Chem. Soc. 1984, 106, 5348–5350.
10. Card, P. J.; Hitz, W. D.; Ripp, K. G. J. Am. Chem. Soc. 1986, 108, 158–161.
11. Zikopoulos, J. N.; Eklund, S. H.; Robyt, J. F. Carbohydr. Res. 1982, 104, 245–251.
12. Karl, H.; Lee, C. K.; Khan, R. Carbohydr. Res. 1982, 101, 31–38.
13. Positron Emission Tomography: Basic Sciences; Bailey, D. L., Townsend, D. W.,
Valk, P. E., Maisey, M. N., Eds.; Springer: London, 2005.
Supplementary data
Supplementary data (copies of proton, carbon and fluorine
spectra for selected compounds) associated with this article can
be found, in the online version, at http://dx.doi.org/10.1016/
j.carres.2012.12.001.
References
14. Barros, M. T.; Maycock, C. D.; Siñeriz, F.; Thomassigny, C. Tetrahedron 2000, 56,
6511–6516.
15. (a) Cai, L.; Lu, S.; Pike, V. W. Eur. J. Org. Chem. 2008, 2853–2873; (b) Mascaretti,
O. A. Aldrichim. Acta 1993, 26, 47–58; (c) Gerstenberger, M. R. C.; Haas, A.
Angew. Chem., Int. Ed. Engl. 1981, 20, 647–667.
16. (a) Liotta, C. L.; Harris, H. P. J. Am. Chem. Soc. 1974, 96, 2250–2252; (b) Pedersen,
C. J. J. Am. Chem. Soc. 1967, 89, 7017–7036; (c) Sam, D. J.; Simmons, H. E. J. Am.
Chem. Soc. 1974, 96, 2252–2253.
1. (a) Bennett, C.; Clayton, S.; Tovell, D. Chem. Ind. 2010, 21–23; (b) O’Hagan, D. J.
Fluorine Chem. 2010, 131, 1071–1081; (c) Filler, R.; Saha, R. Future Med. Chem.
2009, 1, 777–791; (d) Pattan, S. R.; Dighe, N. S.; Shinde, H. V.; Hole, M. B.;
Gaware, V. M. Asian J. Res. Chem. 2009, 2, 376–379; (e) Purser, S.; Moore, P. R.;
Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320–330; (f) Hagmann, W.
K. J. Med. Chem. 2008, 51, 4359–4369; (g) Mueller, K.; Faeh, C.; Diederich, F.
Science 2007, 317, 1881–1886.