A synthesis of 6-deoxy-6-fluorosucrose suitable for PET applications

Article abstract of DOI:10.1016/j.carres.2014.08.015

A new route to 6-deoxy-6-fluorosucrose has been developed. The process proceeds in 8 linear steps in 25% overall yield from sucrose. The steps incorporating fluorine and subsequent deprotection are quite rapid, making the procedure useful in the context o

Full text of DOI:10.1016/j.carres.2014.08.015

Carbohydrate Research 400 (2014) 14–18
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
A synthesis of 6-deoxy-6-fluorosucrose suitable for PET applications
⇑
Xuefeng Gao, 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
Article history:
Received 16 July 2014
Received in revised form 18 August 2014
Accepted 28 August 2014
Available online 21 September 2014
A new route to 6-deoxy-6-fluorosucrose has been developed. The process proceeds in 8 linear steps in
25% overall yield from sucrose. The steps incorporating fluorine and subsequent deprotection are quite
rapid, making the procedure useful in the context of 18F-labeling for PET applications.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Fluorination
Fluorosucrose
Fluorosugar
Kryptofix [2.2.2]
1. Introduction
NCS (N-chlorosuccinimide) in DMSO6 to afford 5 in 64% yield based
on recovered starting material. This means of deprotecting the
In the context of our interest in examining sucrose transport in
plants, we recently reported syntheses of both 60-deoxy-60-
fluorosucrose1 and 10-deoxy-10-fluorosucrose.2 These compounds
are currently being used in their ‘hot’ (18F) form in imaging studies
concerning sucrose transport in maize.3 In order to get more com-
plete information on the nature of sucrose transport, we require a
sucrose derivative that is functionalized in the glucose half of the
molecule. For this purpose, we chose 6-deoxy-6-fluorosucrose
(6-F-sucrose).
A synthesis of 6-F-sucrose was reported by Eklund and Robyt a
number of years ago.4 The key step of the process involved treat-
ment of the sucrose derivative 1 with diethylaminosulfur trifluor-
ide (DAST) in dichloromethane at 30 °C for 22 h (Scheme 1). While
the overall yield from sucrose was 11%, the length of time needed
for fluorination was much too long for our needs. We thus set out
to develop an improved synthesis.
TBDPS group is apparently new, but we have not attempted to
develop it in any way beyond this synthesis. The selectivity is likely
due to steric effects, but a more definitive conclusion would
require a detailed mechanistic investigation.
Compound 5 could be protected with benzoyl chloride to afford
6 essentially quantitatively. Deprotection of the TBDPS ether at
position 6 was accomplished with bromine in methanol7 and the
resulting alcohol was converted to its corresponding triflate under
standard conditions, giving 7 in 74% yield for the two steps.
The last two steps were key with respect to our ultimate goals
for the project. Treatment of 7 with potassium fluoride in the pres-
ence of 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexaco-
sane (K222) gave the corresponding fluoride after 10 min in
refluxing acetonitrile. Global hydrolysis with potassium carbonate
in refluxing methanol afforded 6-deoxy-6-fluorosucrose (8) in only
5 min in a two-step yield of 89%. The product possessed spectral,
chemical, and optical properties that matched those in the litera-
ture. The overall yield was 25% from sucrose over eight steps.
2. Results and discussion
Our synthesis began with the selective protection of the 6 and 60
hydroxy groups of sucrose (3) with tert-butyldiphenylsilyl (TBDPS)
chloride5 followed by perbenzoylation of the remaining hydroxyls
to afford 6,60-(bis)-O-tert-butyldiphenylsilyl-2,3,4,10,30,40-hexa-O-
benzoylsucrose (4) in an overall yield of 61% (Scheme 2). Selective
cleavage of the 60 silyl protecting group was accomplished with
3. Conclusion
We have developed a synthetic protocol to 6-deoxy-6-fluorosu-
crose that is quite suitable for application to an 18F-labeled species.
We will apply the hot compound to studies of sucrose transport in
maize. Results will be reported in due course.
⇑
Corresponding author. Tel.: +1 573 882 1097; fax: +1 573 882 2754.
E-mail address: harmatam@missouri.edu (M. Harmata).
http://dx.doi.org/10.1016/j.carres.2014.08.015
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

X. Gao et al. / Carbohydrate Research 400 (2014) 14–18
15
Scheme 1. Fluorination step in the Eklund–Robyt approach to 6-F-sucrose.
OH
OTBDPS
1. TBDPS-Cl
O
O
HO
HO
BzO
BzO
DMAP (10 mol%)
pyridine, rt, 3 d
2. BzCl, pyridine
rt, 12 h
HO
BzO
OH
O
OBz
O
OH
OTBDPS
O
O
3
4
OH
OBz
HO
BzO
61%
NCS, DMSO
70 oC, 24 h
64% (BRSM)
OTBDPS
O
OTBDPS
O
BzO
BzO
BzCl, pyridine
CH2Cl2, rt, 6 h
BzO
BzO
BzO
OBz
O
BzO
OBz
OBz
O
OH
O
100%
6
O
OBz
BzO
5
OBz
BzO
1. Br2, MeOH
reflux, 2 h
2. Tf2O, 2,6-lutidine
CH2Cl2, -78 o
C
20 min
74% (BRSM)
OTf
F
O
O
BzO
HO
HO
1. KF, K222, MeCN
reflux, 10 min
2. K2CO3, MeOH
reflux, 5 min
89%
BzO
BzO
BzO
HO
OBz
OH
OBz
OH
O
O
O
O
7
8
OBz
OH
HO
Scheme 2. Synthesis of 6-deoxy-6-fluorosucrose.
University, with a Bruker 12 Tesla APEX–Qe FTICR-MS. Optical
rotations were measured with a JASCD DIP-370 digital polarimeter.
4. Experimental section
4.1. General methods
4.2. 6,60-(Bis)-O-tert-butyldiphenylsilylsucrose
All reactions were carried out in oven-dried or flame-dried
flasks under an atmosphere of argon. Acetonitrile, dichlorometh-
ane, and methanol were freshly distilled over calcium hydride.
Analytical thin layer chromatography was performed on normal
and reverse phase silica gel plates impregnated with a UV indica-
tor. Flash chromatography was carried out using 230–400 mesh
silica gel with HPLC grade solvents. 1H and 13C NMR spectra were
recorded on a Bruker DRX 500 (500 MHz for 1H, 125 MHz for 13C)
spectrometer in CDCl3 (TMS as internal standard) or D2O. 19F
NMR was recorded on a Bruker ARX-250 (235.3 MHz for 19F) spec-
trometer 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 spec-
trometer. High-resolution mass spectra were performed by the
College of Science Major Instrumentation Center, Old Dominion
To a solution of 20 g (58.4 mmol) of sucrose in 200 mL pyridine
was added 200 mg of DMAP (10 mol %), followed by 36.3 mL
(140.2 mmol, 2.2 equiv) of TBDPSCl. The solution was stirred at rt
for 3 days, then concentrated under reduced pressure. One hun-
dred mL of EtOAc was added, and the mixture was concentrated
under reduced pressure. The residue was purified by column chro-
matography using 1–2.5% MeOH in EtOAc, which resulted in 29 g
(35.6 mmol, 61% yield) of product as a white solid. This was further
purified by recrystallization from EtOAc, affording 14.85 g
(18.1 mmol, 31% yield) of pure product as a white solid, mp 208–
209 °C. 1H NMR (500 MHz, CDCl3) d 7.67–7.56 (m, 8H), 7.40–7.20
0
0
(m, 12H), 5.41 (d, J1,2 = 3.5 Hz, 1H, H-1), 4.09 (t, J3 ,4 = 7.5 Hz, 1H,
H-30), 4.02 (t, J3 4 = J4 ,5 = 7.5 Hz, 1H, H-40), 3.91–3.73 (m, 5H, H-
60, H-50, H-5, H-6 ), 3.71–3.53 (m, 5H, H-3, H-10, H-4, H-6b), 3.34
0
0
0
0
a

16
X. Gao et al. / Carbohydrate Research 400 (2014) 14–18
(dd, J1,2 = 3.5 Hz, J2,3 = 9.5 Hz, 1H, H-2), 0.96 (s, 9H), 0.95 (s, 9H); 13
C
NMR (500 MHz, CDCl3) d 8.12 (d, J = 7.5 Hz, 2H), 8.00 (d,
NMR (125 MHz, CD3OD) d 136.80, 136.77, 136.74, 136.71, 134.83,
134.51, 134.49, 134.48, 130.78, 130.76, 130.71, 130.69, 128.81,
128.78, 128.73, 128.68, 105.95 (C-20), 93.42 (C-1), 83.95 (C-50),
79.49 (C-30), 77.06 (C-40), 74.95 (C-3), 74.20 (C-5), 73.33 (C-2),
71.33 (C-4), 66.46 (C-60), 64.44 (C-6), 64.36 (C-10), 27.34, 20.09,
20.00; IR (cmꢀ1) 3395, 3305, 3187, 3070, 2976, 2928, 2884, 2855,
1588, 1472, 1461, 1426, 1389, 1363, 1339, 1322, 1300, 1266,
1188,1152, 1102, 1046, 1013, 989, 960, 937, 910, 880, 824, 800,
741, 701, 689; HRMS m/z calcd for (C44H58O11Si2)Na+ 841.3410,
J = 8.0 Hz, 2H), 7.98 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 7.5 Hz, 2H),
7.89 (d, J = 7.5 Hz, 2H), 7.88 (d, J = 7.0 Hz, 2H), 7.77 (d, J = 3.5 Hz,
2H), 7.56 (d, J = 7.5 Hz, 2H), 7.54–7.32 (m, 13H), 7.32–7.22
(m, 7H), 7.15 (d, J = 7.5 Hz, 2H), 7.14 (d, J = 6.5 Hz, 2H), 6.26–6.20
(m, 2H, H-1, H-3), 6.08 (t, J3,4 = J4,5 = 10.0 Hz, 1H, H-4), 6.05–5.99
(m, 2H, H-30, H-40), 5.41 (dd, J2,1 = 3.0 Hz, J2,3 = 10.5 Hz, 1H, H-2),
4.59 (s, 2H, H-10), 4.38 (d, J5,4 = 10.0 Hz, 1H, H-5), 4.25 (s, 1H, H-
50), 3.86–3.80 (m, 1H, H-60a), 3.80–3.72 (m, 1H, H-60b), 3.66 (s,
2H, H-6), 3.05 (t, J6 ,OH = 7.5 Hz, 1H, H-OH), 1.09 (s, 9H). 13C NMR
0
found 841.3404; [
a]
20 = 25.0 (c 1.00, MeOH).
(125 MHz, CDCl3) d 166.53, 165.62, 165.47, 165.43, 165.18,
D
164.59, 135.74, 135.47, 133.46, 133.34, 133.02, 133.00, 132.84,
132.76, 132.73, 129.99, 129.71, 129.67, 129.58, 129.42, 129.28,
129.27, 129.19, 128.81, 128.72, 128.49, 128.43, 128.40, 128.28,
128.19, 128.13, 127.58, 127.41, 103.77 (C-20), 90.70 (C-1), 81.71
(C-50), 77.80 (C-30), 74.41 (C-40), 71.97 (C-2), 71.84 (C-5), 70.33
(C-3), 67.75 (C-4), 65.60 (C-10), 61.03 (C-6), 60.83 (C-60), 26.64,
19.09; IR (cmꢀ1) 3512, 3071, 2931, 2858, 1733, 1602, 1585, 1492,
1472, 1451, 1428, 1390, 1315, 1267, 1178, 1160, 1095, 1070, 1026,
850, 824, 802, 739, 708, 686; HRMS m/z calcd for (C70H64O17Si)Na+
4.3. 6,60-(Bis)-O-tert-butyldiphenylsilyl-2,3,4,10,30,40-hexa-O-
benzoylsucrose (4)
To a solution of 14.85 g (18.1 mmol) of 6,60-(bis)-O-tert-butyldi-
phenylsilylsucrose in 90.7 mL of CH2Cl2 was added 17.6 mL of pyr-
idine (218 mmol, 12 equiv). The solution was stirred vigorously at
rt for 10 min, then 25.3 mL (218 mmol 12 equiv) of benzoyl chlo-
ride was added and the mixture was stirred at rt for 12 h. The solu-
tion was then washed with water and brine, dried with MgSO4, and
concentrated under reduced pressure. One hundred mL of hexanes
was added, and the mixture was concentrated under reduced pres-
sure. The residue was purified by column chromatography (5–20%
EtOAc in hexanes), affording 26.1 g (18.1 mmol, 100% yield) of a
white solid, mp 159–160 °C (recrystallized from MeOH). 1H NMR
(500 MHz, CDCl3) d 8.03 (d, J = 7.5 Hz, 2H), 7.96 (d, J = 8.5 Hz, 2H),
7.94 (d, J = 9 Hz, 2H), 7.88 (d, J = 7.5 Hz, 2H), 7.81 (d, J = 8.0 Hz,
2H), 7.79 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 7.0 Hz, 2H), 7.60–7.12 (m,
34H), 7.06 (t, J = 7.7 Hz, 2H), 6.10 (t, J2,3 = J3,4 = 10.0 Hz, 1H, H-3),
6.02 (d, J1,2 = 3.0 Hz, 1H, H-1), 5.96 (t, J3,4 = J4,5 = 10.0 Hz, 1H,
1227.3805, found 1227.3797; [a]
20 = 21.8 (c 1.00, CHCl3).
D
4.5. 6-O-tert-Butyldiphenylsilyl-2,3,4,10,30,40,60-hepta-O-
benzoylsucrose (6)
To a solution of 12.36 g (10.25 mmol) of 5 in 51.3 mL CH2Cl2
(0.2 M) was added 2.49 mL of pyridine (30.76 mmol, 3.0 equiv) fol-
lowed by 3.57 mL of benzoyl chloride (30.76 mmol, 3.0 equiv) at
room temperature. The reaction was stirred at rt for 6 h, then the
solvent was removed under reduced pressure. The residue was
purified by flash chromatography (SiO2, 20% EtOAc/hexane), which
resulted in 13.4 g (10.25 mmol) of 6, solid foam mp 87–90 °C;
Rf = 0.48, 30% EtOAc/hexanes; 1H NMR (500 MHz, CDCl3) d 8.11
(d, J = 7.5 Hz, 2H), 8.01–7.94 (m, 6H), 7.91 (d, J = 7.5 Hz, 2H), 7.88
(d, J = 7.5 Hz, 2H), 7.85 (d, J = 7.0 Hz, 2H), 7.77 (d, J = 7.0 Hz, 2H),
7.56 (d, J = 7.5 Hz, 2H), 7.54–7.44 (m, 4H), 7.43–7.22 (m, 19H),
7.17–7.10 (m, 4H), 6.26 (t, J3,2 = J3,4 = 10.0 Hz, 1H, H-3), 6.22 (d,
J1,2 = 3.5 Hz, 1H, H-1), 6.09 (t, J4,3 = J4,5 = 10.0 Hz, 1H, H-4), 6.01
H-4), 5.95 (t, J3 ,4 = J4 ,5 = 6.5 Hz, 1H, H-40), 5.86 (d, J3 ,4 = 6.0 Hz,
0
0
0
0
0
0
1H, H-30), 5.40 (dd, J1,2 = 3.5 Hz, J2,3 = 10.5 Hz, 1H, H-2), 4.63 (d,
J1 ,1 b = 12.0 Hz, 1H, H-10a), 4.58 (d, J1 ,1 b = 12.0 Hz, 1H, H-10b),
0
0
0a
0a
4.31 (m, 2H, H-5, H-50), 3.92 (dd, J5 ,6 = 5.5 Hz, J6 ,6 b = 11.0 Hz,
0
0
0
a
0a
1H, H-60a), 3.88 (dd, J5 ,6 b = 5.5, J6 ,6 b = 11.0 Hz, 1H, H-60b), 3.52
0
0
0
0a
(d, J6 ,6b = 12.0 Hz, 1H, H-6
a), 3.43 (d, J6 ,6b = 12.0 Hz, 1H, H-6b),.
a
a
1.01 (s, 9H), 0.97 (s, 9H); 13C NMR (125 MHz, CDCl3) d 165.72,
165.65, 165.55, 165.44, 164.96, 164.69, 135.71, 135.54, 135.50,
135.47, 133.34, 133.21, 133.08, 133.02, 132.96, 132.93, 132.81,
132.77, 132.70, 130.07, 129.88, 129.81, 129.78, 129.72, 129.65,
129.55, 129.49, 129.43, 129.36, 129.18, 129.04, 128.87, 128.52,
128.37, 128.27, 128.22, 128.17, 127.67, 127.64, 127.60, 127.41,
103.93 (C-20), 90.71 (C-1), 81.17 (C-50), 77.75 (C-30), 75.26 (C-40),
71.40 (C-2, C-5), 70.96 (C-3), 68.10 (C-4), 65.31 (C-10), 63.74
(C-60), 61.00 (C-6), 26.68, 26.64, 19.11, 19.02; IR (cmꢀ1) 3071,
2959, 2931, 2858, 1966, 1733, 1602, 1585, 1492, 1472, 1451,
1428, 1390, 1362, 1315, 1265, 1177, 1106, 1070, 1026, 824, 802,
739, 708; HRMS m/z calcd for (C86H82O17Si2)Na+ 1465.4983, found
(d, J3 ,4 = 6.5 Hz, 1H, H-30), 5.95 (t, J4 ,3 = J4 ,5 = 6.5 Hz, 1H, H-40),
5.47 (dd, J2,1 = 3.5 Hz, J2,3 = 10.0 Hz, 1H, H-2), 4.70–4.58 (m, 5H,
H-10(2H), H-50, H-60(2H)), 4.53 (d, J5,4 = 10.0 Hz, 1H, H-5), 3.85 (d,
0
0
0
0
0
0
J6 ,6b = 12.0 Hz, 1H, H-6a), 3.76 (d, J6b,6 = 12.0 Hz, 1H, H-6b), 1.08
a a
(s, 9H, H-tBu); 13C NMR (125 MHz, CDCl3) d 165.79, 165.73,
165.66, 165.30, 165.27, 165.19, 164.67, 135.67, 135.45, 133.46,
133.35, 133.14, 133.00, 132.96, 132.89, 132.81, 130.03, 129.75,
129.74, 129.69, 129.60, 129.57, 129.52, 129.39, 129.36, 129.31,
129.18, 128.74, 128.64, 128.55, 128.36, 128.21, 128.13, 127.56,
127.43, 104.14 (C-20), 90.77 (C-1), 78.72 (C-50), 77.15 (C-30), 75.85
(C-40), 71.59 (C-5), 71.54 (C-2), 70.66 (C-3), 68.02 (C-4), 64.84
(C-10), 64.12 (C-60), 61.22 (C-6), 26.66, 19.11; IR (cmꢀ1) 3070,
2959, 2857, 1732, 1602, 1585, 1492, 1472, 1451, 1428, 1315,
1269, 1177, 1160, 1107, 1070, 1026, 823, 802, 739, 708, 686; HRMS
m/z calcd for (C77H68O18Si)Na+ 1331. 4067, found 1331.4705;
1465.4968; [a]
20 = 8.2 (c 1.00, CHCl3).
D
4.4. 6-O-tert-Butyldiphenylsilyl-2,3,4,10,30,40-hexa-O-
benzoylsucrose (5)
[a]
20 = 16.2 (c 1.00, CHCl3).
D
To a solution of 26.1 g of 4 (18.1 mmol) in 181 mL of DMSO
(0.1 M), 7.25 g (54.3 mmol, 3 equiv) of N-chlorosuccinimide (NCS)
was added. The reaction was stirred at 70 °C for 24 h and
monitored by TLC (small amount of solution was transferred to a
test tube, diluted with EtOAc, and washed with water; analyzed
by TLC with 30% EtOAc in hexanes, for 4 Rf = 0.5, for 5 Rf = 0.43.)
To the reaction was added 200 mL of EtOAc at rt and the mixture
was stirred for 1 min. The EtOAc layer was washed with water,
brine, and dried over MgSO4. The crude product was purified by
flash chromatography (SiO2, 30% EtOAc/hexanes) affording 12 g
of a white solid (55%, 64% yield based on recovered starting
material), along with 3.46 g of recovered starting material. 1H
4.6. 2,3,4,10,30,40,60-hepta-O-benzoylsucrose (1)
To a 1 L flask charged with 400 mL MeOH was added 10.56 g
(8.06 mmol) of 6. The mixture was refluxed with vigorous stirring
for 10 min. Then to the solution was added 2.08 mL (40.3 mmol,
5 equiv) of Br2 and the mixture was refluxed for another 2 h, after
which the reaction was quenched with a saturated sodium hydro-
sulfite solution. The solvent was removed under reduced pressure.
The residue was extracted with CH2Cl2, dried over MgSO4, and con-
centrated under reduced pressure. The crude product was purified
by flash chromatography (30% EtOAc in hexanes, Rf = 0.27), which

X. Gao et al. / Carbohydrate Research 400 (2014) 14–18
17
resulted in 4.78 g of product (4.46 mmol, 55%, 86% yield based on
recovered SM) as a viscous oil (3.79 g 6 was recovered), which
foamed upon evacuation (mp 82–88 °C). 1H NMR (500 MHz, CDCl3)
d 8.22 (d, J = 7.5 Hz, 2H), 8.03–7.96 (m, 6H), 7.86 (d, J = 7.5 Hz, 2H),
7.84 (d, J = 7.5 Hz, 2H), 7.80 (d, J = 7.5 Hz, 2H), 7.61–7.47 (m, 7H),
7.42–7.28 (m, 10H), 7.25 (t, J = 7.5 Hz, 2H), 7.11 (t, J = 7.5 Hz, 2H),
6.24 (t, J3,2 = J3,4 = 10.0 Hz, 1H, H-3), 6.16 (d, J1,2 = 3.5 Hz, 1H, H-
the solvent was removed by reduced pressure, and the product was
purified by flash chromatography (SiO2, 30% EtOAc in hexanes,
Rf = 0.38), to afford 78 mg of a semisolid (0.0727 mmol, 89% yield).
1H NMR (500 MHz, CDCl3) d 8.20 (d, J = 7.5 Hz, 2H), 8.04–7.96 (m,
6H), 7.85 (d, J = 7.5 Hz, 2H), 7.83 (d, J = 7.0 Hz, 2H), 7.76 (d,
J = 8.0 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.57–7.47 (m, 6H),
7.43–7.29 (m, 10H), 7.26 (t, J = 7.5 Hz, 2H), 7.12 (t, J = 7.5 Hz, 2H),
6.24–6.17 (m, 2H, H-1, H-3), 6.05–5.96 (m, 2H, H-30, H-40), 5.64
(t, J4,3 = J4,5 = 10.0 Hz, 1H, H-4), 5.40 (dd, J2,1 = 3.5 Hz,
J2,3 = 10.0 Hz, 1H, H-2), 4.76–4.70 (m, 2H, H-60), 4.66–4.38 (m,
6H, H-5, H-6, H-10, H-50); 13C NMR (125 MHz, CDCl3) d 166.05,
165.63, 165.46, 165.42, 165.40, 165.29, 165.04, 133.60, 133.59,
133.44, 133.25, 133.10, 133.09, 133.03, 130.16, 129.87, 129.84,
129.73, 129.72, 129.58, 129.43, 129.20, 129.07, 128.88, 128.73,
128.66, 128.55, 128.47, 128.44, 128.33, 128.31, 128.29, 128.26,
128.21, 104.20 (C-20), 90.39 (C-1), 80.89 (d, J = 173.75 Hz, 1C, C-
6), 78.78 (C-50), 77.39 (C-30), 75.90 (C-40), 71.07 (C-2), 70.02 (d,
J = 18.75 Hz, 1C, C-5), 70.01 (C-3), 68.08 (d, J = 6.25 Hz, 1C, C-4),
65.03 (C-10), 64.14 (C-60); 19F NMR (235 MHz, CDCl3) d ꢀ232.81
(dt, J = 23.5, 47.0 Hz, 1F); IR (cmꢀ1) 3063, 2961, 1728, 1602,
1584, 1492, 1451, 1377, 1315, 1265, 1177, 1095, 1070, 1026,
802, 707, 686; HRMS m/z calcd for (C61H49FO17)Na+ 1095.2846,
1), 6.03 (d, J3 ,4 = 6.0 Hz, 1H, H-30), 6.00 (t, J4 ,3 = J4 ,5 = 6.0 Hz, 1H,
0
0
0
0
0
0
H-40), 5.53 (t, J4,3 = J4,5 = 10.0 Hz, 1H, H-4), 5.41 (dd, J2,1 = 3.5 Hz,
0
0a
,
50
0a
J2,3 = 10.0 Hz, 1H, H-2), 4.83 (dd, J6
= 6.5 Hz, J6 ,6 b = 12.0 Hz,
1H, H-60a), 4.73 (dd, J6 b,5 = 5.0 Hz, J6 b,6 = 12.0 Hz, 1H, H-60b),
0
0
0
0
a
4.65 (t, J5 ,4 = J5 6 = 6.0 Hz, 1H, H-50), 4.62 (d, J1 ,1 b = 12.0 Hz, 1H,
0
0
0
0
0
0a
H-10a), 4.56 (d, J1 ,1 b = 12.0 Hz, 1H, H-10b), 4.44 (d, J5,4 = 10.0 Hz,
0
0a
1H, H-5), 3.74 (dd, J6 ,6b = 12.0 Hz, J6 ,5 = 8.0 Hz, 1H, H-6a),
a
a
3.67–3.61 (m, 1H, H-6b), 2.82 (t, JOH,6 = 7.0 Hz, 1H, H-OH); 13C
NMR (125 MHz, CDCl3) d 166.20, 165.95, 165.67, 165.48, 165.44,
165.39, 165.25, 133.59, 133.51, 133.21, 133.14, 133.07, 132.99,
130.17, 129.95, 129.85, 129.82, 129.72, 129.68, 129.51, 129.34,
129.18, 129.10, 128.82, 128.69, 128.61, 128.54, 128.45, 128.42,
128.31, 128.29, 128.27, 128.22, 128.18, 104.25 (C-20), 90.57 (C-1),
78.96 (C-50), 77.29 (C-40), 76.20 (C-30), 71.66 (C-5), 71.20 (C-2),
69.83 (C-3), 69.11 (C-4), 64.85 (C-10), 64.35 (C-60), 60.92 (C-6); IR
(cmꢀ1) 3530, 3063, 2961, 1729, 1602, 1584, 1492, 1451, 1379,
1316, 1270, 1178, 1095, 1070, 1026, 854, 803, 708, 686; HRMS
m/z calcd for (C61H50O18)Na+ 1093.2889, found 1093.2878;
found 1095.2836; [a]
20 = 22.6 (c 1.00, CHCl3).
D
4.9. 6-Deoxy-6-fluorosucrose (8)
[a]
20 = 20.6 (c 1.00, CHCl3).
D
To a solution of 1.07 g (1.00 mmol) of 2 in 20 mL MeOH (0.05 M)
was added 138 mg of K2CO3 (1.00 mmol, 1.0 equiv) at rt. The solu-
tion was then refluxed for 5 min. The reaction was monitored with
TLC. The solvent was then removed under reduced pressure. The
product was purified by flash chromatography (SiO2, 10% H2O in
CH3CN, Rf = 0.28), to afford 346 mg of 8 (1.00 mmol, 100% yield).
The product was recrystallized from water, mp 181–182 °C; 1H
NMR (500 MHz, D2O) d 5.43 (d, J1,2 = 3.5 Hz, 1H, H-1), 4.78 (s, 7H,
4.7. 6-O-Trifluoromethanesulfonyl-2,3,4,10,30,40,60-hepta-O-
benzoylsucrose (7)
To a solution of 3.93 g of 1 (3.67 mmol, 0.05 M) in 73 mL of
dichloromethane (0.05 M) at ꢀ78 °C was added 765
lL of 2,6-luti-
dine (6.60 mmol, 1.8 equiv) and followed by 925 L trifluorometh-
l
anesulfonic anhydride (5.50 mmol, 1.5 equiv). The reaction was
stirred for 20 min, and then the solution was filtered through a
short plug of silica gel, and washed with CH2Cl2. The resulting solu-
tion was concentrated under reduced pressure, and then purified
by flash chromatography (SiO2, 30% EtOAc/hexanes, Rf = 0.40), to
afford 3.8 g of 7 as a white solid foam (86% yield); mp 87–92 °C;
1H NMR (500 MHz, CDCl3) d 8.18 (d, J = 7.5 Hz, 2H), 8.05–7.96 (m,
6H), 7.88–7.82 (m, 4H), 7.79 (d, J = 8.0 Hz, 2H), 7.61 (t, J = 7.5 Hz,
1H), 7.57–7.46 (m, 6H), 7.42–7.27 (m, 10H), 7.24 (t, J = 7.5 Hz,
2H), 7.11 (t, J = 7.5 Hz, 2H), 6.26–6.20 (m, 2H, H-1, H-3), 6.00–
5.95 (m, 2H, H-30, H-40), 5.66 (t, J4,3 = J4,5 = 10.0 Hz, 1H, H-4), 5.39
(dd, J2,1 = 3.5 Hz, J2,3 = 10.0 Hz, 1H, H-2), 4.79–4.62 (m, 6H, H-5,
OH), 4.69 (dd, J6 ,6b = 11.0 Hz, J6 ,5 = 3.5 Hz, 1H, H-6a), 4.63 (d,
a
a
J6 ,6b = 11.0 Hz, 1H, H-6b), 4.22 (d, J3 ,4 = 9.0 Hz, 1H, H-30), 4.08–
0
0
a
3.97 (m, 2H, H-5, H-40), 3.92–3.86 (m, 1H, H-50), 3.84–3.73 (m,
3H, H-3, H-60), 3.67 (s, 2H, H-10), 3.58 (dd, J2,1 = 3.5 Hz,
J2,3 = 10.0 Hz, 1H, H-2), 3.50 (t, J4,3 = J4,5 = 10.0 Hz, 1H, H-4); 13C
NMR (125 MHz, D2O) d 106.43 (C-20), 94.81 (C-1), 85.01 (d,
J = 167.5 Hz, 1C, C-6), 84.07 (C-50), 78.95 (C-30), 76.73 (C-40),
75.06 (C-3), 74.02 (d, J = 17.5 Hz, 1C, C-5), 73.63 (C-2), 71.12 (d,
J = 7.5 Hz, 1C, C-4), 65.11 (C-60), 63.95 (C-10); 19F NMR (235 MHz,
D2O) d ꢀ234.83 (dt, J = 28.2, 47.0 Hz, 1F); IR (cmꢀ1) 3576, 3338,
3008, 2975, 2935, 1650, 1454, 1435, 1411, 1388, 1365, 1346,
1332, 1277, 1235, 1207, 1159, 1126, 1112, 1068, 1049, 1014,
988, 939, 921, 862, 735, 680; HRMS m/z calcd for (C12H21FO10)Na+
H-10, H-50, H-60), 4.53 (d, J6 ,6b = 11.0 Hz, 1H, H-6
a), 4.46 (d,
a
J6 ,6b = 11.0 Hz, 1H, H-6b); 13C NMR (125 MHz, CDCl3) d 165.98,
a
165.50, 165.41, 165.35, 165.31, 165.17, 164.90, 133.69, 133.61,
133.54, 133.23, 133.14, 133.09, 129.99, 129.84, 129.81, 129.79,
129.68, 129.60, 129.52, 129.30, 129.05, 128.81, 128.78, 128.70,
128.56, 128.50, 128.44, 128.32, 128.29, 128.20, 128.18, 118.43 (q,
J = 317.92 Hz, 1C), 104.92 (C-20), 90.82 (C-1), 79.21 (C-50), 77.63
(C-30), 76.25 (C-40), 72.83 (C-6), 70.86 (C-2), 69.57 (C-3), 68.63
(C-5), 67.94 (C-4), 64.52 (C-10), 63.83 (C-60); IR (cmꢀ1) 3064,
2958, 1729, 1602, 1585, 1492, 1452, 1419, 1316, 1267, 1214,
1178, 1144, 1094, 1070, 1026, 983, 935, 845, 803, 707, 686; HRMS
m/z calcd for (C62H49F3O20S)Na+ 1225.2382, found 1225.2368;
367.1011, found 367.1010; [
1.00, MeOH).
a] a]
20 = 60.0 (c 1.00, H2O), [ 20 = 63.4 (c
D D
Acknowledgments
This work was generously supported by a grant from the
Department of Energy (DE-SC0002040). We thank Ms. Carissa S.
Hampton (University of Missouri-Columbia) for assistance in
preparing this manuscript.
[a]
20 = 19.6 (c 1.00, CHCl3).
D
Supplementary data
4.8. 6-Deoxy-6-fluoro-2,3,4,10,30,40,60-hepta-O-benzoylsucrose
(2)
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2014.08.
015.
To a solution of 98.3 mg of 7 (0.0817 mmol) in 8.2 mL of CH3CN
at room temperature was added 7.1 mg (0.1226 mmol, 1.5 equiv)
of KF, followed by 46 mg K222 (0.1226 mmol, 1.5 equiv). The solu-
tion was then refluxed for 10 min. Once the reaction was complete,
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