Synthesis of radioiodine-labeled 2-phenylethyl 1-thio-β-D-galactopyranoside for imaging of LacZ gene expression

Article abstract of DOI:10.1016/S0008-6215(02)00359-2

A potent inhibitor of β-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-β-D-galactopyranoside (PETG), was radioiodinated for noninvasive imaging of LacZ gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2-(4-bromophenyl)ethanethiol was prepared and attached to the C-1 position of β-D-galactose pentaacetate under conditions that resulted in the exclusive formation of the β anomer. The bromo group of PETG was converted to the tributylstannyl group where radioiododemetallation was carried out. Radioiodine-labeled PETG tetraacetate was purified by HPLC, which can be used as a prodrug for biological evaluation or hydrolyzed to 2-(4-[¹²³I/¹²⁵I]iodophenyl)ethyl 1-thio-β-D-galactopyranoside ([¹²³I/¹²⁵I]7) under basic conditions. The resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical yield (decay-corrected) and with specific activity of 46-74 GBq/μmol.

Full text of DOI:10.1016/S0008-6215(02)00359-2

Carbohydrate Research 338 (2003) 29–34
www.elsevier.com/locate/carres
Synthesis of radioiodine-labeled 2-phenylethyl
1-thio-b-
D-galactopyranoside for imaging of LacZ gene expression
Joon Hun Choi, Yearn Seong Choe,* Kyung-Han Lee, Yong Choi, Sang Eun Kim,
Byung-Tae Kim
Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan Uni6ersity School of Medicine, 50 Ilwon-dong, Kangnam-ku,
Seoul 135-710, Republic of Korea
Received 11 July 2002; accepted 23 September 2002
Abstract
A potent inhibitor of b-galactosidase (EC 3.2.1.23), 2-phenylethyl 1-thio-b-
noninvasive imaging of LacZ gene expression. In order to introduce radioiodine to the phenyl ring of PETG, 2-(4-bro-
-galactose pentaacetate under conditions that resulted
D-galactopyranoside (PETG), was radioiodinated for
mophenyl)ethanethiol was prepared and attached to the C-1 position of b-
D
in the exclusive formation of the b anomer. The bromo group of PETG was converted to the tributylstannyl group where
radioiododemetallation was carried out. Radioiodine-labeled PETG tetraacetate was purified by HPLC, which can be used as a
prodrug for biological evaluation or hydrolyzed to 2-(4-[123I/125I]iodophenyl)ethyl 1-thio-b- -galactopyranoside ([123I/125I]7) under
D
basic conditions. The resulting radioiodine-labeled PETG was obtained in overall 62% radiochemical yield (decay-corrected) and
with specific activity of 46–74 GBq/mmol. © 2002 Elsevier Science Ltd. All rights reserved.
Keywords: Gene expression; b-Galactosidase; 2-Phenylethyl 1-thio-b-
D
-galactopyranoside; Radioiodine; SPECT
1. Introduction
animals is not possible. As a more sensitive and nonin-
vasive approach, nuclear medicine technology has been
applied to monitoring of reporter gene expression in
living systems using specific radiotracers and positron
emission tomography (PET) or single photon emission
computed tomography (SPECT).3 These imaging tech-
niques utilize radiolabeled inhibitors of an enzyme for
measurement of the enzyme density as well as the
radiolabeled substrates for measurement of the enzyme
activity. The most intensively studied system is the
herpes simplex virus type 1 thymidine kinase (HSV
1-tk) reporter gene system that uses uracil nucleosides
and acycloguanosine derivatives, such as 2%-deoxy-2%-
fluoro-1-b-
(FIAU) and 8-[18F]fluoro-9-[[2-hydroxy-1-(hydroxy-
methyl)ethoxy]methyl]guanine (FGCV). Cytosine
deaminase and dopamine D2 receptor reporter gene
systems have been also investigated using 5-
[18F]fluorocytosine and 3-(2%-[18F]fluoroethyl)spiperone
(FESP), respectively. Recently LacZ gene expression
was evaluated using 2%-[18F]fluorodeoxylactose, a b-
galactosidase substrate.4 Enzymatic synthesis of this
radiotracer was troublesome due to its long incubation
With the advance of molecular biology, gene expression
has been extensively studied using reporter genes. The
most commonly used reporter systems include b-galac-
tosidase, b-glucuronidase, chloramphenicol acetyltrans-
ferase, and firefly luciferase.1 Among these, the lacZ
gene, which encodes E. coli b-galactosidase, is the most
attractive reporter gene due to ready availability of the
gene, transferring vectors and assaying reagents. Since
this reporter gene produces b-galactosidase that hy-
drolyzes lactose to galactose and glucose, lacZ gene
expression can be investigated utilizing the b-galactosi-
dase substrates that exhibit either fluorescence or lu-
minescence after they are turned over by the enzyme.2
However, such methods are limited to in vitro experi-
ments that usually require destruction of cell mem-
branes, and application for in vivo monitoring in living
D
-arabinofuranosyl-5-[123I]iodouracil
* Corresponding author. Tel.: +82-2-34102623; fax: +82-
2-34102639
E-mail address: yschoe@samsung.co.kr (Y.S. Choe).
0008-6215/03/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00359-2

30
J.H. Choi et al. / Carbohydrate Research 338 (2003) 29–34
time and low yield, and above all, its biodistribution
data suggested the lack of penetration of this radio-
tracer through the cell membranes.
In this study, therefore, PETG, a potent competitive
inhibitor of b-galactosidase with Ki ranging from 0.94–
2.5 mM,5–7 was radioiodinated for noninvasive imaging
of LacZ gene expression.
varying proportions depending on the reaction condi-
tions (Scheme 1). The reaction in chloroform at room
temperature for 1 h afforded both 4a and 4b (a and b
anomers in a 33:17 ratio11) in a total yield of 73.9%. On
the other hand, the b anomer 4b was solely produced in
81.9% yield when the reaction was carried out in a 3:2
mixture of chloroform and diethyl ether at low temper-
ature for 3 days.12 Since the PETG has the b configura-
tion, the latter conditions were employed to produce
the b anomer (4b) stereoselectively. The bromo group
on the phenyl ring of 4b was then substituted with a
tributylstannyl group to give 5 that was further con-
verted to an iodo group on 6. Deprotection of 6 was
readily carried out at room temperature under basic
conditions to give 7.
2. Results and discussion
Radioiodine was introduced to the phenylethylthio
moiety rather than to the sugar part of PETG, a potent
inhibitor of b-galactosidase, in order to minimize per-
turbation of its binding affinity to the enzyme. In order
to carry out radioiododemetallation, a bromo group
was introduced at the C-4 position of the phenyl ring,
and was further converted to a tributylstannyl group at
later step.
2-(4-Bromophenyl)ethanethiol (3) was prepared from
4-bromophenethyl alcohol in three steps in high yields.
Although the Mitsunobu reaction does not require
activation of a hydroxyl group for displacement with a
sulfur nucleophile,8 the desired product 3 can be con-
taminated with PPh3 due to their similar polarities.
Therefore, the hydroxyl function was activated by con-
version to the mesylate 1, followed by displacement
with a suitable sulfur nucleophile. Reduction of the
thioester 2 gave the desired thiol 3.9,10 The thiol was
Radioiodination of 5 with Na[123I/125I]I in the pres-
ence of Chloramine-T gave [123I/125I]6 quantitatively
(Scheme 2). The reaction produced a polar radioactive
compound when an excess amount of Chloramine-T
was used. Although the byproduct has not been iden-
tified, it may be a compound derived from sulfur oxida-
tion. The tetraacetyl compound [123I/125I]6 was purified
by high performance liquid chromatography (HPLC)
(Fig. 1) and could be used as a prodrug for biological
studies, since it is expected to cross the cell membranes
and then undergo hydrolysis intracellularly to the [123I/
125I]7. This was the case when 1,3,4,6-tetraacetyl-2-de-
oxy-2-[18F]fluoro- -glucose ([18F]AFDG) was incubated
D
with the cells, which readily penetrated the cell mem-
branes and was intracellularly converted to [18F]FDG.13
The identity of [123I/125I]6 was confirmed by HPLC
then introduced into the C-1 position of b-
D-galactose
pentaacetate, which gave the a and b anomers, in
Scheme 1. Reagents and conditions: (a) CH3SO2Cl, i-Pr2NEt, CH2Cl2; (b) Cs2CO3, CH3COSH, DMF; (c) LiAlH4, THF; (d)
BF3·OEt2, CHCl3–ether; (e) Pd(PPh3)4, (SnBu3)2, toluene; (f) I2, CHCl3; (g) 1.0 N NaOH–MeOH.
Scheme 2. Reagents and conditions: (a) Na[125I/123I]I, Chloramine-T; (b) 0.1 N NaOH–EtOH.

J.H. Choi et al. / Carbohydrate Research 338 (2003) 29–34
31
final radiotracer was 62%, with a radiochemical purity
\98.5% and specific activity of 46–74 GBq/mmol.
In conclusion, radioiodine-labeled PETG was synthe-
sized in high yield for noninvasive imaging of LacZ
gene expression. Its prodrug, [123I/125I]6, was also pre-
pared in the course of synthetic route of [123I/125I]7 to
facilitate the penetration through cell membranes.
3. Experimental
3.1. Materials and methods
Fig. 1. HPLC profile of 1,3,4,6-tetraacetyl 4-[123I/125I]iodo-
PETG. HPLC conditions: 80:19:1 n-hexanes–CH2Cl2–2-
propanol; flow rate, 4.0 mL/min; tR 9.57 min. The eluant was
simultaneously monitored by a UV detector (254 nm) and a
NaI(Tl) radioactivity detector.
1H NMR spectra were performed on a JNM-LA 300
spectrometer (JEOL Ltd) at 300 MHz, and chemical
shifts (l) are reported in ppm downfield from Me4Si as
an internal reference. Both EI and FAB mass spectra
were obtained on a JMS-700 Mstation (JEOL Ltd)
instrument in the positive-ion mode. Ethyl acetate or
MeOH was used as the solvent, and 3-nitrobenzyl
alcohol satd with NaI served as matrix for the FAB
mass spectra. TLC was performed on E. Merck F254
silica plates, and the sugar compounds were visualized
by UV illumination or staining with 1:9 H2SO4–EtOH.
Radio-TLC was performed on a Bioscan radio-TLC
scanner. HPLC was carried out on a Thermo Separa-
tion Products System with a semipreparative column
(Alltech Econosil silica gel, 10 mm, 10×250 mm).
Analysis of the final radiotracer was performed on
reversed-phase HPLC using an analytical column
(YMC C18, 5 mm, 4.6×250 mm). The eluant was
simultaneously monitored by a UV detector (254 nm)
and a NaI(Tl) radioactivity detector. Radioactivity was
measured in a dose calibrator.
Reaction solvents were distilled prior to use. All
other chemicals were purchased from Aldrich Chemical
Company (Milwaukee, WI, USA) and used without
further purification. Na[123I]I was purchased from Ko-
rea Cancer Center Hospital (Seoul, Korea) and
Na[125I]I from NEN Life Science Products, Inc.
(Boston, MA, USA). Flash column chromatography
was performed using E. Merck silica gel 60 (230–400
mesh).
Fig. 2. (A) Radio thin-layer chromatogram of radioiodine-la-
beled PETG. Developing solvents: 19:1 CH3CN–H2O; Rf
0.66; (B) HPLC analysis. HPLC conditions: 7:3 H2O–
CH3CN; flow rate, 1.0 mL/min; tR 9.59 min. The eluant was
simultaneously monitored by a UV detector (254 nm) and a
NaI(Tl) radioactivity detector.
3.2. 2-(4-Bromophenyl)ethyl methanesulfonate (1)
To a soln of 4-bromophenethyl alcohol (0.300 g, 1.49
mmol) in CH2Cl2 (7.0 mL) was added N,N%-diisopropyl-
ethylamine (0.31 mL, 1.79 mmol) at room temperature
(rt) for 30 min. The solution was cooled to −20 °C and
stirred at the same temperature for 2 h after methane-
sulfonyl chloride (0.14 mL, 1.79 mmol) was added
dropwise. At the end of the reaction, the solution was
poured into a mixture of 5 mL of water and 2 mL of 1
N HCl. The organic layer was separated, and the aq
layer was extracted with CH2Cl2 (10 mL×2). The
co-injection with unlabeled compound 6. [123I/125I]6 was
further hydrolyzed to [123I/125I]7 in 0.1 N NaOH–EtOH
at room temperature, and the product was purified by
use of a C-18 Sep-Pak® cartridge. The [123I/125I]7 was
identified by co-elution with unlabeled compound 7 on
both radio-thin layer chromatography (TLC) and
HPLC (Fig. 2(A and B)). Radiochemical yield of the

32
J.H. Choi et al. / Carbohydrate Research 338 (2003) 29–34
combined organic extracts were washed with 20 mL of
satd NaHCO3 and dried over anhyd MgSO4. Flash
column chromatography (3:1 n-C6H14–EtOAc) af-
forded 2-(4-bromophenyl)ethyl methanesulfonate (1) in
99.5% yield (0.414 g) as a white solid: 1H NMR
(CDCl3): l 7.45 (d, J 8.3 Hz, 2 H), 7.12 (d, J 8.3 Hz, 2
H), 4.39 (t, J 6.7 Hz, 2 H), 3.01 (t, J 6.7 Hz, 2 H), 2.89
(s, 3 H). EIMS: m/z 280 (M+, 81Br), 278 (M+, 79Br).
HRMS: Calcd for C9H1179BrO3S: 277.9612. Found:
277.9600.
was allowed to proceed at rt in dark room for 1 h.
Excess BF3·OEt2 was decomposed by the addition of
cold water (10 mL), and the mixture was then extracted
with EtOAc (5 mL×3). The combined organic extracts
were dried over anhyd MgSO4. Flash column chro-
matography (3:1 n-C6H14–EtOAc) afforded the a
anomer (4a) in 48.8% yield (0.037 g) and the b anomer
(4b) in 25.1% yield (0.019 g).
3.5.2. Method B (only b anomer). To b-D-galactose
pentaacetate (0.398 g, 1.02 mmol) dissolved in CHCl3 (6
mL) was added Et2O (4 mL). The mixture was cooled
to 0 °C, and to it was added a soln of 3 (0.200 g, 0.92
mmol) in CHCl3 (3 mL), followed by BF3·OEt2 (1.3
mL). The reaction was allowed to proceed at −10 to
0 °C for 3 days. Excess BF3·OEt2 was decomposed by
the addition of cold water (20 mL), and the mixture
was extracted with EtOAc (15 mL×3). The combined
organic extracts were dried over anhyd MgSO4. Flash
column chromatography (3:1 n-C6H14–EtOAc) af-
forded the only b anomer (4b) in 81.9% yield (0.413 g)
as a colorless sticky syrup.
3.3. S-[2-(4-Bromophenyl)ethyl]thioacetate (2)
Methanesulfonate 1 (0.700 g, 2.51 mmol) was dissolved
in anhyd DMF (25 mL) under N2, and then Cs2CO3
(2.45 g, 7.53 mmol) was added. After stirring the sus-
pension for 30 min at rt, thiolacetic acid (0.54 mL, 7.53
mmol) was added into the suspension. The mixture was
then stirred for another 30 min, poured into water, and
extracted with EtOAc (15 mL×3). The combined or-
ganic extracts were washed with 20 mL of water and
dried over anhyd Na2SO4. Flash column chromatogra-
phy (20:1 n-C6H14–EtOAc) afforded the S-[2-(4-bro-
mophenyl)ethyl]thioacetate (2) in 90.8% yield (0.590 g)
as a pale-yellow solid with a foul odor: 1H NMR
(CDCl3): l 7.42 (d, J 8.4 Hz, 2 H), 7.09 (d, J 8.4 Hz, 2
H), 3.08 (m, 2 H), 2.82 (m, 2 H), 2.32 (s, 3 H). EIMS:
m/z 260 (M+, 81Br), 258 (M+, 79Br). HRMS: Calcd for
C10H1179BrOS: 257.9714. Found: 257.9698.
1
3.5.2.1. Spectral data for 4a. H NMR (CDCl3): l
7.42 (d, J 8.3 Hz, 2 H), 7.06 (d, J 8.3 Hz, 2 H), 5.76 (d,
J 5.1 Hz, 1 H, H-1), 5.44 (m, 1 H), 5.27 (dd, J 10.7, 5.4
Hz, 1 H), 5.19 (dd, J 10.7, 3.2 Hz, 1 H), 4.54 (t, J 6.4
Hz, 1 H), 4.10 (m, 2 H), 2.78 (m, 4 H, ꢀSCH2CH2ꢀ),
2.15, 2.06, 1.99, 1.98 (4s, 12 H, ꢀCOCH3). FABMS:
m/z 571 (M++Na, 81Br), 569 (M++Na, 79Br).
HRMS: Calcd for C22H2779BrO9SNa: 569.0457. Found:
569.0447.
3.4. 2-(4-Bromophenyl)ethanethiol (3)
A soln of 2 (0.500 g, 1.93 mmol) in THF (20 mL) was
added dropwise to a suspension of LiAlH4 (0.293 g,
7.72 mmol) in THF (10 mL) at 0 °C under N2. The
mixture was stirred at rt for 30 min, and the excess
LiAlH4 was decomposed by the addition of cold water
(10 mL), followed by 1 N HCl (20 mL). The reaction
mixture was extracted with EtOAc (15 mL×3), and the
combined organic extracts were washed with 20 mL of
water and dried over anhyd Na2SO4. Flash column
chromatography (20:1 n-C6H14–EtOAc) gave the 2-(4-
bromophenyl)ethanethiol (3) in 93.8% yield (0.393 g) as
a pale-yellow liquid with a foul odor: 1H NMR
(CDCl3): l 7.42 (d, J 8.3 Hz, 2 H), 7.07 (d, J 8.3 Hz, 2
H), 2.87 (m, 2 H), 2.77 (m, 2 H), 1.36 (t, J 7.8 Hz, 1 H).
EIMS: m/z 218 (M+, 81Br), 216 (M+, 79Br). HRMS:
Calcd for C8H979BrS: 215.9608. Found: 215.9595.
1
3.5.2.2. Spectral data for 4b. H NMR (CDCl3): l
7.42 (d, J 8.3 Hz, 2 H), 7.09 (d, J 8.3 Hz, 2 H), 5.44 (d,
J 3.2 Hz, 1 H), 5.25 (t, J 9.9 Hz, 1 H), 5.04 (dd, J 9.9,
3.2 Hz, 1 H), 4.47 (d, J 9.8 Hz, 1 H, H-1), 4.14 (m, 2
H), 3.92 (m, 1 H), 2.99 (m, 2 H), 2.88 (m, 2 H), 2.15,
2.05, 2.03, 1.99 (4s, 12 H, ꢀCOCH3). FABMS: m/z 571
(M++Na, 81Br), 569 (M++Na, 79Br). HRMS: Calcd
for C22H2779BrO9SNa: 569.0457. Found: 569.0461.
3.6. 2-(4-Tributylstannylphenyl)ethyl 2,3,4,6-tetra-O-
acetyl-1-thio-b-D-galactopyranoside (5)
To a stirred soln of 4b (0.122 g, 0.22 mmol) in
C6H5CH3 (4 mL) were added sequentially tetra-
kis(triphenylphosphine)palladium(0) (0.025 g, 0.022
mmol) and hexabutylditin (0.56 mL, 1.1 mmol). The
reaction mixture was stirred at 120 °C for 17 h under
N2 and then filtered through a Celite column. The
resulting solution was concentrated in vacuo and
purified by flash column chromatography (3:1 n-
C6H14–EtOAc) to give the tributylstannyl compound 5
3.5. 2-(4-Bromophenyl)ethyl 2,3,4,6-tetra-O-acetyl-1-
thio-a,b-D-galactopyranoside (4a and 4b)
3.5.1. Method A (mixture of a and b anomers). To
-galactose pentaacetate (0.062 g, 0.16 mmol) in
b-
D
1
CHCl3 (3 mL) were added thiol 3 (0.030 g, 0.14 mmol),
followed by BF3·OEt2 (0.20 mL, 1.6 mmol). Reaction
in 43.8% yield (0.073 g) as a colorless sticky syrup: H
NMR (CDCl3): l 7.39 (d, J 4.8 Hz, 2 H), 7.17 (d, J 4.8

J.H. Choi et al. / Carbohydrate Research 338 (2003) 29–34
33
Hz, 2 H), 5.44 (m, 1 H), 5.26 (t, J 6.0 Hz, 1 H), 5.04
(dd, J 2.1, 6.0 Hz, 1 H), 4.48 (d, J 6.0 Hz, 1 H, H-1),
4.14 (m, 2 H), 3.92 (m, 1 H), 2.91 (m, 4 H), 2.16, 2.06,
2.03, 1.99 (4s, 12 H, ꢀCOCH3), 1.54 (m, 6 H), 1.33 (m,
6 H), 1.04 (m, 6 H), 0.90 (m, 9 H). FABMS: m/z 781
(M++Na). HRMS: Calcd for C34H54NaO9SSn:
781.2408. Found: 781.2370.
mg, 2.19 mmol) in water (50 mL) was added to the
reaction mixture that was then stirred at rt. The iodina-
tion was terminated after 20 min by an addition of
saline (2 mL), and the radioactive compounds were
extracted with EtOAc (1.5 mL×3). The organic layer
was passed through a Pasteur pipet containing Na2SO4,
and the solvent was removed under a gentle stream of
N2. The residue was redissolved in 1 mL of HPLC
solvents and purified by HPLC using 80:19:1 n-C6H14–
CH2Cl2–2-propanol at a flow rate of 4.0 mL/min. The
product [123I/125I]6 was eluted at 9.57 min. The solvents
were removed, and a portion was taken out for biolog-
ical studies. The other portion was redissolved in EtOH
(200 mL) and diluted with 0.1 N aq NaOH (100 mL).
The reaction mixture was stirred for 10 min, and excess
NaOH was neutralized by the addition of 0.1 N aq HCl
(80 mL). The solution was then diluted with 10 mL of
water and passed through a C-18 Sep-Pak® cartridge.
The cartridge was washed with water (10 mL), followed
by EtOH (1.5 mL) that eluted the product. The solvent
was removed and the residue was redissolved in saline.
3.7. 2-(4-Iodophenyl)ethyl 2,3,4,6-tetra-O-acetyl-1-thio-
b-D-galactopyranoside (6)
To a soln of 5 (0.027 g, 0.036 mmol) in CHCl3 (3 mL)
was added dropwise a soln of iodine in CHCl3 (0.1 M)
until iodine color persisted. The solution was stirred for
15 h at rt. Excess iodine was quenched by a soln of KF
in MeOH (1 M, 0.1 mL), and the mixture was stirred
with 5% aq sodium bisulfite soln (0.3 mL) for 5 min.
The solution was then extracted with EtOAc (5 mL×
3), and the combined organic extracts were then dried
over anhyd MgSO4. Flash column chromatography (2:1
n-C6H14–EtOAc) afforded the iodo compound 6 in
68.2% yield (0.015 g) as a white solid: 1H NMR
(CDCl3): l 7.62 (d, J 8.3 Hz, 2 H), 6.96 (d, J 8.3 Hz, 2
H), 5.44 (m, 1 H), 5.25 (t, J 9.8 Hz, 1 H), 5.04 (dd, J
3.4, 9.9 Hz, 1 H), 4.46 (d, J 9.8 Hz, 1 H, H-1), 4.14 (m,
2 H), 3.92 (m, 1 H), 2.92 (m, 4 H), 2.15, 2.05, 2.03, 1.99
(4s, 12 H, ꢀCOCH3). FABMS: m/z 617 (M++Na).
HRMS: Calcd for C22H27INaO9S: 617.0318. Found:
617.0297.
[
123I/125I]7 (144.3 or 41 MBq) was obtained in overall
62% radiochemical yield (decay-corrected) and a radio-
chemical purity \98.5%. An aliquot was analyzed by
reversed-phase HPLC using 7:3 water–MeCN at a flow
rate of 1.0 mL/min, and specific activity of [123I/125I]7
was determined by using a standard curve obtained
from 7 with different concentrations injected on HPLC
versus UV absorbance at 254 nm. Another portion of
[
123I/125I]7 was co-injected with unlabeled compound 7
3.8. 2-(4-Iodophenyl)ethyl 1-thio-b-
D-galactopyranoside
on HPLC to confirm its identity.
(7)
To a soln of 6 (0.015 g, 0.025 mmol) in MeOH (2 mL)
was added 1.0 N aq NaOH (1.0 mL) at 0 °C. After
stirring the reaction mixture for 30 min at rt, the
solution was poured into water (5 mL) and extracted
with EtOAc (10 mL×3). The combined organic ex-
tracts were dried over anhyd MgSO4. Flash column
chromatography (10:1 CH2Cl2–MeOH) afforded the
Acknowledgements
This work was supported in part by the National
Mid- and Long-term Nuclear R&D Program Grants
cM2-0204190027-02A0701-00111
(K.H.L.)
and
cM2-0204190027-02A0701-00150 (Y.S.C.) of the Ko-
rean Ministry of Science and Technology.
2-(4-iodophenyl)ethyl 1-thio-b- -galactopyranoside (7)
D
in 49% yield (0.0052 g) as a white solid: 1H NMR
(CDCl3): l 7.61 (d, J 8.3 Hz, 2 H), 6.98 (d, J 8.3 Hz, 2
H), 4.31 (d, J 9.3 Hz, 1 H, H-1), 3.97 (m, 1 H), 3.79 (m,
2 H), 3.61 (t, J 9.3 Hz, 1 H), 3.51 (m, 2 H), 2.93 (m, 4
H). FABMS: m/z 449 (M++Na). HRMS: Calcd for
C14H19INaO5S: 448.9896. Found: 448.9884.
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