Synthesis and taste properties of 4,1′,4′,6′-tetrahalodeoxysncrose analogues

Article abstract of DOI:10.1081/CAR-120021700

The synthesis of a series of 1,4,6-trideoxy-1,4,6-trihalo-β-D-hexulofuranosyl 4-deoxy-4-halo-α-D-hexopyranosides is described. The 4-chloro-, 4-bromo- and 4-iodo-4-deoxy-β-D-fructofuranosyl analogues were synthesized from a 3′,4′-lyxo-epoxide using the re

Full text of DOI:10.1081/CAR-120021700

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Synthesis and Taste Properties of
4,1′,4′,6′‐Tetrahalodeoxysucrose Analogues
A. S. Sofian Md & C. Kuan Lee
To cite this article: A. S. Sofian Md & C. Kuan Lee (2003) Synthesis and Taste Properties of
4,1′,4′,6′‐Tetrahalodeoxysucrose Analogues, Journal of Carbohydrate Chemistry, 22:3-4,
185-206, DOI: 10.1081/CAR-120021700
To link to this article: http://dx.doi.org/10.1081/CAR-120021700
Published online: 28 Oct 2011.
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Date: 31 August 2016, At: 02:31

JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 22, Nos. 3 & 4, pp. 185–206, 2003
Synthesis and Taste Properties of
4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
*
A. S. Md Sofian and C. Kuan Lee
Department of Chemistry, National University of Singapore,
Kent Ridge, Singapore
ABSTRACT
The synthesis of a series of 1,4,6-trideoxy-1,4,6-trihalo-b-D-hexulofuranosyl 4-deoxy-
4-halo-a-D-hexopyranosides is described. The 4-chloro-, 4-bromo- and 4-iodo-4-
deoxy-b-D-fructofuranosyl analogues were synthesized from a 3’,4’-lyxo-epoxide
using the respective alkali metal halides. The corresponding 4-halodeoxytagatofura-
nosyl analogues, on the other hand, were obtained by direct halide displacement of the
4’-O-trifluoromethanesulfonyl derivative, which was derived by regioselective
sulfonylation of 1,6-di-O-trityl-b-D-fructofuranosyl 6-O-trityl-a-D-glucopyranoside
via its stannylene acetal. The sweetness intensities of these tetrahalodeoxy compounds
strongly suggest that both size and configuration of the halogen substituents at C-4 and
C-4’ are critical for sweetness enhancement.
Key Words: Sweetness; Tetrahalodeoxysucrose analogues; Halogenation; Sucrose.
*
Correspondence: A. S. Md Sofian, Department of Chemistry, National University of Singapore,
Kent Ridge, Singapore 119260; E-mail: scip8192@nus.edu.sg.
185
DOI: 10.1081/CAR-120021700
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2003 by Marcel Dekker, Inc.

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Sofian and Lee
INTRODUCTION
The Shallenberger-Acree-Kier AH,B,g-hypothesis[1,2] is the most widely accepted
model used to explain sweet taste chemoreception. For sucrose and its derivatives, the
AH,B,g-glucophore appears to span the two sugar rings and both are involved in
recognition, since glucopyranosyl and fructofuranosyl derivatives are generally less sweet
than sucrose and definitely very much less sweet than halodeoxy sucrose analogues.
The location of the g-site(s) in sucrose is still not very clear, but since halogenation
of some or all the C-4, 1’, 4’ and 6’ positions of sucrose produced derivatives with
enhanced sweetness, the halogen(s) at one or more of these positions could, therefore,
be acting as the g-site(s).
If indeed the halogen(s) function as the g-site(s), the stereochemistry at C-4 and/or
C-4’ is critical for sweet taste induction. For example, 1,6-dichloro-1,6-dideoxy-b-D-
fructofuranosyl 4-chloro-4-deoxy-a-D-galactopyranoside[3,4] (sucralose) is 650 times
sweeter than sucrose, but its gluco-isomer is only 100 times sweeter.[5] Recently, 1,4,6-
trichloro-1,4,6-trideoxy-b-D-tagatofuranosyl 4-chloro-4-deoxy-a-D-galactopyranoside[6]
was reported to be only about 205 times sweeter than sucrose, whereas its C-4’
epimer, 1,4,6-trichloro-1,4,6-trideoxy-b-D-fructofuranosyl 4-chloro-4-deoxy-a-D-galac-
topyranoside[7] is 2200 times sweeter.
Continuing our research programme on the structure-sweetness relationship of
halodeoxy sucroses, we now report the synthesis and taste characteristics of a series
of 1,4,6-trideoxy-1,4,6-trihalo-b-D-fructofuranosyl 4-deoxy-4-halo-a-D-glucopyrano-
sides, 1,4,6-trideoxy-1,4,6-trihalo-b-D-fructofuranosyl 4-deoxy-4-halo-a-D-galactopyra-
nosides, and 1,4,6-trideoxy-1,4,6-trihalo-b-D-tagatofuranosyl 4-deoxy-4-halo-a-D-galac-
topyranosides.
RESULTS AND DISCUSSION
A convenient starting material for the synthesis of the target compounds 29–31 is
3,4-anhydro-1,6-di-O-trityl-b-D-lyxo-hexulofuranosyl 2,3,4-tri-O-acetyl-6-O-trityl-a-D-
glucopyranoside[8] (1) (Scheme 1). This was converted to the corresponding 4-halo-
deoxy fructofuranosyl derivatives by regioselective epoxide ring-opening reaction[8]
with lithium chloride ( ! 2), lithium bromide ( ! 3), and sodium iodide ( ! 4) in
dimethylformamide, in the presence of acetic acid. The 4’-halo-3’-hydrin structures for
1
2–4 were determined from H NMR spectra of 2–4 and their acetylated derivatives 5–
7. The signals due to H-4’ appeared as triplets at dꢀ 4.2 in the spectra of 2–4. These
signals resonate at lower field (dꢀ 4.5) after acetylation (5–7), suggesting the presence
of a halogen substituent at C-4’. The characteristic downfield shift of a doublet at
dꢀ 5.9 (5–7) from dꢀ 4.5 (2–4) revealed the position of acetylation to be at C-3’. The
13C NMR spectra of 2, 3 and 4 also showed that the resonance due to C-4’ has shifted
upfield by ꢀ 1.5 to 35.5 ppm.
Detritylation of compounds 5–7 in acetic acid-dichloromethane (1:1) in the
presence of conc HCl at 0°C gave 8–10 in good yields ( ꢀ 70%). Heating of 8–10
in iso-butyl methyl ketone (MIBK) in the presence of acetic acid resulted in a
migration of the acetyl group from C-4 to C-6.[9] After tritylation of the reaction
mixtures, the migrated products were isolated as 1’,6’-di-O-trityl ethers 14–16,

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
187
Scheme 1. (a) for 2: LiCl/AcOH, DMF, 120°C; for 3: LiBr/AcOH, DMF, 120°C; for 4: NaI/
AcOH, DMF, 120°C; (b) Ac2O, pyr; (c) AcOH-CH2Cl2 (1:1), conc HCl, 0°C; (d) MIBK, AcOH,
110°C; (e) TrCl, pyr.
whereas unchanged starting materials (8–10) were recovered as 6,1’,6’-tri-O-trityl
derivatives 5–7.
The conversion of 14–16 into 4-chloro-4-deoxy sucrose analogues 20–22, as
shown in Scheme 2, involved the epimerization of the hydroxyl group at C-4 using
trifluoromethanesulfonyl anhydride-sodium nitrite[10–12] (17–19), followed by trifla-
tion, and then nucleophilic displacement with lithium chloride (20–22, respectively).
The gluco-configuration of the resultant products was confirmed from the signal due to

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Sofian and Lee
Scheme 2. (f) Tf2O, pyr/CH2Cl2; (g) NaNO2, DMF, rt; (h) LiCl, acetone, rt; (i) TPP/CCl4, pyr; (j)
NaOMe, MeOH, 0°C.
H-4 in their 1H NMR data (d ꢀ 3.7, J3,4 = J4,5
=
ꢀ 10.0 Hz). The presence of a
chlorine substituent on C-4 was deduced from their 13C NMR and MS spectra.
Detritylation ( ! 23–25), chlorination ( ! 26–28) and finally deacetylation gave the
target molecules, 29–31.
The synthesis of 1,4,6-tribromo-1,4,6-trideoxy-b-D-fructofuranosyl 4-deoxy-4-
fluoro-, (38) and 4-iodo-a-D-galactopyranoside (39) is shown in Scheme 3. The C-4
fluorodeoxy galactosucrose derivative (32) was obtained by reaction of the cor-
responding 4-O-triflate of 15 with tris(dimethylamino)sulfur (trimethylsilyl)difluoride
(TASF) while reaction with potassium iodide in dichloromethane gave the corres-
ponding iodo derivative, (33). Detritylation ( ! 34, 35), and subsequent bromination
( ! 36, 37) and deacetylation then afforded the free sugars, 38 and 39.
Regioselective sulfonylation of 1,6-di-O-trityl-b-D-fructofuranosyl 6-O-trityl-a-D-
glucopyranoside,[9] to give 4’-O-triflate,[13] 40 via its stannylene acetal[14] offers an
efficient route towards 4’-deoxy-4’-halo-tagatosucrose analogues (Scheme 4). Nucleo-
philic displacement of the C-4’ triflate group in 40 with lithium bromide and potassium

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
189
Scheme 3. (a) Tf2O, pyr /CH2Cl2; (b) for 32: TASF, CH2Cl2, 40°C; for 33: KI, acetone, rt; (c)
AcOH-CH2Cl2 (1:1), conc HCl, 0°C; (d) LiBr, acetone, 40°C; (e) NaOMe, MeOH, 0°C.
iodide, followed by acetylation gave 41[13] and 42, respectively. Detritylation ( ! 43,
44), and then migration of the acetyl group from C-4 to C-6 afforded 45 and 46,
respectively. Chlorination at C-4, 1’ and 6’ ( ! 47, 48) proceeded via nucleophilic
displacement of the corresponding 4,1’,6’-tri-O-triflate derivatives with lithium chloride.
1
The galacto configuration of 47 and 48 was confirmed from their H NMR spectra.
H-4 appears as a doublet of a doublet (J3,4 = ꢀ 3.5 Hz J4,5 = ꢀ 1.0 Hz) at d 4.54.
Conventional Zemple´n deacetylation furnished 49 and 50.
Treatment of 40 with TASF did not give the desired C-4’-fluoro derivative; instead,
after acetylation, the 3’,4’-lyxo-epoxide,[8] 1 was isolated. It appears that the basicity of
the fluoride anion facilitates formation of an alkoxide at C-3’, which then displaces the
C-4’ triflate group to form the lyxo epoxide.
Taste panel evaluation showed that 4-fluoro- and 4-iodo-1’,4’,6’-tribromo-
4,1’,4’,6’-tetradeoxygalactosucrose, 38 and 39, are about 200 and 520 times sweeter
than sucrose, respectively. It is interesting that the corresponding 4-bromo- and 4-
chloro isomers are very much sweeter (7500 and 7000 ꢁ sucrose, respectively).[15–
17]
The size of a halogen substituent at C-4 of 4,1’,4’,6’-tetrahalodeoxygalactosucrose
derivatives thus appears to be important. The significant difference in sweetness
between 4-chloro-[7] and 4-fluoro-1’,4’,6’-trichloro-4,1’,4’,6’-tetrahalodeoxygalactosu-
ucrose[16,17] (2200 and 200 times sweeter than sucrose, respectively) further
illustrates the importance of size of the halogen substituent at C-4 in galactosucroses
on sweetness.

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Sofian and Lee
Scheme 4. (a) n-Bu2SnO, toluene, azeotropic distillation; (b) Tf2O, pyr/CH2Cl2; (c) for 41: LiBr,
acetone, rt; Ac2O, pyr; for 42: KI, acetone, rt; Ac2O, pyr; (d) AcOH-CH2Cl2 (1:1), conc HCl, 0°C;
(e) MIBK, AcOH, 110°C; (f) Tf2O, pyr/CH2Cl2; LiCl, acetone; (g) NaOMe, MeOH, rt.
In contrast to galactosucrose derivatives, all the corresponding 4,1’,4’,6’-tet-
rahalodeoxysucrose derivatives showed much lower sweetness intensities (190 to 370
times). These results indicate the importance of configuration of the halogen substituents
at C-4. Furthermore, the results also suggested that there is a correlation between
sweetness of these compounds and hydrophobicities of their halogen substituents at C-4’.
Surprisingly, both 4-bromo-1,6-dichloro-1,4,6-trideoxy-b-D-tagatofuranosyl 4-
chloro-4-deoxy-a-D-galactopyranoside (49) and 1,6-dichloro-1,4,6-trideoxy-4-iodo-b-
D-tagatofuranosyl 4-chloro-4-deoxy-a-D-galactopyranoside (50) are bitter, unlike
1,4,6-trichloro-1,4,6-trideoxy-b-D-tagatofuranosyl 4-chloro-4-deoxy-a-D-galactopyrano-
side,[6] which was reported to have a sweetness of 205 times relative to sucrose.
A discussion of the taste panel assessment and structure-sweetness relationship will
be reported in a forthcoming paper elsewhere.

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
EXPERIMENTAL
191
General methods. Melting points were determined with a Thermo Galen Hot
Stage Microscope. Optical rotations were measured with a Perkin Elmer 241
polarimeter at 26°C. NMR spectra were recorded at 298K in CDCl3 (unless otherwise
1
specified) on a Bruker DPX 300 spectrometer (300.13 MHz for H and 75.47 MHz for
13C). Mass spectra were recorded on a Finnigan TSQ 7000 (ion trap) spectrometer
using electron spray ionization (ESI) with a spray voltage of 4.5 KV. The elemental
composition of ions was determined with a resolution of 7000 (10% valley definition).
Flash chromatography was performed on Silica Gel 60 (0.63–0.200 nm, Merck). Thin-
layer chromatography was run on glass plates precoated with silica gel 60F254 (Merck,
Darmstadt, Germany); detection was effected by observation under short wavelength
UV light (254 nm), then spraying with 10% sulphuric acid in ethanol and charring them
on a hot plate.
4-Chloro-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-acetyl-6-O-tri-
tyl- -D-glucopyranoside (2). A solution of 1 (10.5 g, 8.91 mmol) in DMF (60 mL)
was heated overnight at 110°C with AcOH (1 mL) and LiCl (8.90 g, 0.21 mol). After
all starting material had reacted as indicated by TLC (ethyl acetate-hexane, 1:2), DMF
was removed under reduced pressure at 50°C. The residue was taken up in
dichloromethane, filtered and the organic layer washed successively with satd aq
NaHCO3 and brine. It was dried (Na2SO4), filtered and concentrated to a syrup. Flash
column chromatography (ethyl acetate-hexane, 1:3) gave 2 (7.10 g, 66%): mp 128–
1
130°C (methanol); [a]D + 53° (c 2.45, CHCl3); H NMR d 1.57, 1.76, 1.86 (s, 9H,
3 ꢁ CH3), 2.73–3.39 (m, 7H, H-1’a,b, H-5’, H-6a,b, and H-6’a,b), 3.93–3.99 (m, 1H,
H-5), 4.20 (t, 1H, J3’,4’ = J4’,5’ = 9.7 Hz, H-4’), 4.47 (t, 1H, H-3’), 4.71 (dd, 1H,
J1,2 = 4.0 Hz, J2,3 10.0 Hz, H-2), 4.97 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.17 (t,
1H, H-3), 5.69 (d, 1H, H-1) and 7.11–7.39 (m, 45H, Ar-H). 13C NMR d 170.2, 169.2,
169.0 (3 ꢁ COCH3), 143.6, 143.4, 128.6–126.9 (Ar-C), 104.8 (C-2’), 88.7 (C-1),
87.1 (CPh3) 80.9 (C-5’), 79.1 (C-3’), 70.2, 69.8, 69.2, 68.4 (C-2, 3, 4, 5), 64.5, 61.8,
61.6 (C-1’, 6, 6’), 58.5 (C-4’) and 20.5, 20.3, 20.1 (3 ꢁ COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 1235.4324:1237.4295. Found: 1235.4277:
1237.4323.
4-Bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-acetyl-6-O-tri-
tyl- -D-glucopyranoside (3). Compound 1 (10.2 g, 8.66 mmol) in DMF (60 mL) was
treated with AcOH (1 mL) and LiBr (12.9 g, 0.15 mol) as described above. Flash
column chromatography (ethyl acetate-hexane, 1:3) gave 3 (7.65 g, 71%): mp 135–
1
137°C (methanol); [a]D + 53° (c 1.58, CHCl3); H NMR d 1.57, 1.77, 1.86 (s, 9H,
3 ꢁ CH3), 2.73–3.42 (m, 7H, H-1’a,b, H-6a,b, H-6’a,b and OH), 4.02–4.08 (m, 2H,
H-5, 5’), 4.20 (t, 1H, J3’,4’ = J4’,5’ = 10.0 Hz, H-4’), 4.54 (t, 1H, H-3’), 4.71 (dd, 1H,
J1,2 = 4.0 Hz, J2,3 = 10.0 Hz, H-2), 4.98 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.17
(t,1 H, H-3), 5.72 (d, 1H, H-1) and 7.11–7.39 (m, 45H, Ar-H). 13C NMR d 170.2, 169.2,
169.0 (3 ꢁ COCH3), 143.6, 143.4, 128.6–126.9 (Ar-C), 105.0 (C-2’), 88.9 (C-1), 87.2,
87.1 (CPh3), 81.5 (C-5’), 79.9 (C-3’), 70.4, 70.0, 69.4, 68.6 (C-2, 3, 4, 5), 64.7, 62.0, 61.7
(C-1’, 6, 6’), 48.3 (C-4’) and 20.7, 20.5, 20.3 (3 ꢁ COCH3). HRMS-ESI (positive
mode): calcd for [M + Na] + 1279.3819:1281.3799. Found: 1279.3782:1281.3795.

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Sofian and Lee
4-Deoxy-4-iodo-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-acetyl-6-O-trityl-
-D-glucopyranoside (4). Treatment of 1 (10.5 g, 8.94 mmol) with NaI (30 g, 0.2
mol) as described for 2 gave, after column chromatography (ethyl acetate-hexane, 1:3),
1
4 (8.5 g, 73%): 123–125°C (methanol); [a]D + 51° (c 1.62, CHCl3); H NMR d 1.67,
1.87, 1.95 (s, 9H, 3 ꢁ CH3), 2.84–3.54 (m, 7H, H-1’a,b, H-5, H-6a,b and H-6’a,b),
4.22–4.31 (m, 2H, H-4’, 5), 4.64–4.71 (m, 1H, H-3’), 4.81 (dd, 1H, J1,2 = 4.0 Hz,
J2,3 = 10.1 Hz, H-2), 5.09 (t, 1H, J3,4 = J4,5 = 10.1 Hz, H-4), 5.27 (t, 1H, H-3), 5.85
(d, 1H, H-1) and 7.21–7.50 (m, 45H, Ar-H). 13C NMR d 170.2, 169.2, 169.0
(3 ꢁ COCH3), 143.6, 143.4, 128.8–127.0 (Ar-C), 105.2 (C-2’), 88.9 (C-1), 87.2, 87.1,
87.0 (CPh3), 82.9 (C-5’), 81.6 (C-3’), 70.4, 70.0, 69.4, 68.5 (C-2, 3, 4, 5), 64.7, 62.0,
61.5 (C-1’, 6, 6’), 23.7 (C-4’) and 20.6, 20.5, 20.3 (3 ꢁ COCH3). HRMS-ESI (positive
mode): calcd for [M + Na] + 1327.3680. Found: 1327.3656.
3-O-Acetyl-4-chloro-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-
acetyl-6-O-trityl- -D-glucopyranoside (5). Acetylation of 2 (8.4 g, 6.93 mmol) in
pyridine with acetic anhydride gave 5 (7.4 g, 85%): mp 108–110°C (methanol); [a]D
1
+ 41° (c 0.90, CHCl3); H NMR d 1.63, 1.67, 1.86, 1.87 (s, 12H, 4 ꢁ CH3), 2.95–
3.42 (m, 6H, H-1’a,b, H-6a,b and H-6’a,b), 4.02–4.08 (m, 2H, H-5, 5’), 4.53 (t, 1H,
J3’,4’ = J4’,5’ = 9.4 Hz, H-4’), 4.67 (dd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.0 Hz, H-2), 5.12–
5.16 (m, 2H, H-3, 4), 5.76 (d, 1H, H-1), 5.86 (d, 1H, H-3’) and 7.12–7.40 (m, 45H, Ar-
H). 13C NMR d 170.4, 169.2, 169.1, 169.0 (4 ꢁ COCH3), 143.6, 143.5, 143.4, 128.7–
127.1 (Ar-C), 103.4 (C-2’), 88.6 (C-1), 87.2, 86.7 (CPh3), 81.7 (C-5’), 77.8 (C-3’),
70.7, 69.7, 69.6, 68.9 (C-2, 3, 4, 5), 65.1, 61.8, 61.5 (C-1’, 6, 6’), 55.5 (C-4’) and
20.8, 20.7, 20.4, (4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for [M + Na] +
1277.4430:1279.4400. Found: 1277.4493:1279.4433.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-
acetyl-6-O-trityl-a-D-glucopyranoside (6). Acetylation of 3 (7.5 g, 5.97 mmol) in
the usual manner gave 6 (6.7 g, 86%): mp 133–135°C (methanol); [a]D + 40° (c 1.27,
1
CHCl3); H NMR d 1.63, 1.67, 1.85, 1.87 (s, 12H, 4 ꢁ CH3), 2.96–3.44 (m, 6H, H-
1’a,b, H-6a,b and H-6’a,b), 4.06–4.15 (m, 2H, H-5, 5’), 4.52 (t, 1H, J3’,4’ = J4’,5’
=
10.0 Hz, H-4’), 4.67 (dd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.0 Hz, H-2), 5.11–5.20
(m, 2H, H-3, 4), 5.80 (d, 1H, H-1), 5.92 (d, 1H, H-3’) and 7.13–7.41 (m, 45H,
Ar-H). 13C NMR d 170.4, 169.2, 169.1, 169.0 (4 ꢁ COCH3), 143.6, 143.5, 128.5–
126.9 (Ar-C), 103.5 (C-2’), 88.5 (C-1), 87.2, 86.7 (CPh3), 82.0 (C-5’), 78.1 (C-3’),
70.7, 69.6, 69.5, 68.8 (C-2, 3, 4, 5), 65.1, 61.7, 61.3 (C-1’, 6, 6’), 44.3 (C-4’) and
20.7, 20.5, 20.4, (4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for [M + Na] +
1321.3925:1323.3905. Found: 1321.3940:1323.3920.
3-O-Acetyl-4-deoxy-4-iodo-1,6-di-O-trityl- -D-fructofuranosyl 2,3,4-tri-O-
acetyl-6-O-trityl- -D-glucopyranoside (7). Acetylation of 4 (8.3 g, 6.36 mmol) in
the usual manner gave 7 (7.45 g, 87%): 205–207°C (methanol); [a]D + 47° (c 1.09,
1
CHCl3); H NMR d 1.64, 1.67, 1.85, 1.87 (s, 12H, 4 ꢁ CH3), 2.95–3.48 (m, 6H,
H-1’a,b, H-6a,b and H-6’a,b), 4.04–4.08 (m, 1H, H-5’), 4.17–4.22 (m, 1H, H-5), 4.47
(t, 1H, J3’,4’ = J4’,5’ = 10.4 Hz, H-4’), 4.68 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.0 Hz,
H-2), 5.11–5.24 (m, 2H, H-3, 4), 5.83 (d, 1H, H-1) 5.93 (d, 1H, H-3’) and 7.12–7.41
(m, 45H, Ar-H). 13C NMR d 170.4, 169.2, 169.1, 169.0 (4 ꢁ COCH3), 143.6, 143.4,

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
193
128.7–127.0 (Ar-C), 103.7 (C-2’), 88.5 (C-1), 87.2, 87.1, 86.6 (CPh3), 83.4 (C-5’),
79.8 (C-3’), 70.8, 69.6, 69.4, 68.8 (C-2, 3, 4, 5), 65.2, 61.5, 61.1 (C-1’, 6, 6’), 20.7,
20.6, 20.4 (4 ꢁ COCH3) and 18.5 (C-4’). HRMS-ESI (positive mode): calcd for
[M + Na] + 1369.3786. Found: 1369.3809.
3-O-Acetyl-4-chloro-4-deoxy- -D-fructofuranosyl 2,3,4-tri-O-acetyl- -D-gluco-
pyranoside (8). To a solution of 5 (4.30 g, 3.43 mmol) in ice-cold dichlor-
omethane-acetic acid (1:1, 100 mL), was added drop-wise conc HCl (1.0 mL). After all
starting material had reacted (1.5 h), the solution was neutralized (Na2CO3), filtered,
concentrated and chromatographed (ethyl acetate-hexane, 2:1) to give 8 (1.32 g, 73%)
1
as a colourless syrup; [a]D + 10° (c 0.59, CHCl3); H NMR d 1.95, 1.97, 2.00, 2.22 (s,
12H, 4 ꢁ CH3), 3.45–3.92 (m, 7H, H-1’a,b, H-5’, H-6a,b and H-6’a,b), 4.09–4.13 (m,
1H, H-5), 4.52 (t, 1H, J3’,4’ = J4’,5’ = 9.4 Hz, H-4’), 4.77 (dd, 1H, J1,2 = 3.8 Hz,
J2,3 = 10.4 Hz, H-2), 4.84 (t, 1H, J3,4 = J4,5 = 10.4 Hz, H-4), 5.22 (d, 1H, H-3’), 5.39
(t, 1H, H-3) and 5.57 (d, 1H, H-1). 13C NMR d 171.4, 170.1, 170.0, 169.9
(4 ꢁ COCH3), 104.1 (C-2’), 89.8 (C-1), 82.8 (C-5’), 80.0 (C-3’), 71.3, 70.4, 69.2, 68.7
(C-2, 3, 4, 5), 63.9, 61.6, 58.3 (C-1’, 6, 6’), 53.9 (C-4’) and 20.6, 20.5, 20.5
(4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for [M + Na] + 551.1143:553.1114.
Found: 551.1136:553.1098.
3-O-Acetyl-4-bromo-4-deoxy- -D-fructofuranosyl 2,3,4-tri-O-acetyl- -D-gluco-
pyranoside (9). Treatment of 6 (6.96 g, 5.36 mmol) as for 8 gave, after column
chromatography (ethyl acetate-hexane, 2:1), 9 (2.17 g, 71%) as a yellowish syrup; [a]D
1
+ 11° (c 0.53, CHCl3); H NMR d 1.95, 1.97, 2.00, 2.22 (s, 12H, 4 ꢁ CH3), 3.51–
3.87 (m, 6H, H-1’a,b, H-6a,b and H-6’a,b), 3.99–4.13 (m, 2H, H-5, 5’), 4.49 (t, 1H,
J3’,4’ = J4’,5’ = 10.0 Hz, H-4’), 4.77 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.0 Hz, H-2), 4.84
(t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.29 (d, 1H, H-3’), 5.40 (t, 1H, H-3) and 5.57
(d, 1H, H-1). 13C NMR d 171.4, 170.1, 170.0, 169.5 (4 ꢁ COCH3), 104.4 (C-2’), 89.8
(C-1), 83.2 (C-5’), 80.3 (C-3’), 71.3, 70.4, 69.2, 68.7 (C-2, 3, 4, 5), 63.9, 61.6, 58.3
(C-1’, 6, 6’), 42.6 (C-4’) and 20.6, 20.5 (4 ꢁ COCH3). HRMS-ESI (positive mode):
calcd for [M + Na] + 595.0638:597.0618. Found: 595.0624:597.0611.
3-O-Acetyl-4-deoxy-4-iodo- -D-fructofuranosyl 2,3,4-tri-O-acetyl- -D-glucopy-
ranoside (10). Treatment of 7 (5.43 g, 4.03 mmol) as for 8 gave, after flash
chromatography (ethyl acetate-hexane, 2:1), 10 (1.57 g, 63%) as a colourless syrup;
1
[a]D + 14° (c 1.54, CHCl3); H NMR d 1.95, 1.97, 1.98, 2.00 (s, 12H, 4 ꢁ CH3),
3.48–3.76 (m, 6H, H-1’a,b, H-6a,b and H-6’a,b), 3.84–3.88 (m, 1H, H-5’), 4.09–4.13
(m, 1H, H-5), 4.45 (t, 1H, J3’,4’ = J4’,5’ = 10.4 Hz, H-4’), 4.78 (dd, 1H, J1,2 = 3.5 Hz,
J2,3 = 10.0 Hz, H-2), 4.85 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.31 (d, 1H, H-3’), 5.39
(t, 1H, H-3) and 5.58 (d, 1H, H-1). 13C NMR d 171.3, 170.1, 170.0, 169.9
(4 ꢁ COCH3), 104.6 (C-2’), 89.8 (C-1), 84.8 (C-5’), 81.7 (C-3’), 71.3, 70.4, 69.2, 68.7
(C-2, 3, 4, 5), 63.9, 61.5, 58.2 (C-1’, 6, 6’), 20.6, 20.5 (4 ꢁ COCH3) and 16.8 (C-4’).
HRMS-ESI (positive mode): calcd for [M + Na] + 643.0500. Found: 643.0494.
3-O-Acetyl-4-chloro-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-glucopyranoside (14). A solution of 8 (1.02 g, 1.93 mmol) in MIBK
(20 mL) and AcOH (1.0 mL) was heated under reflux, and the progress of the reaction

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1
was monitored by H NMR. After most starting material had reacted for ꢀ 8 h, the
mixture was concentrated by co-distilling several times with MeOH. The yellow syrupy
residue was dissolved in pyridine (20 mL) and stirred with trityl chloride (2.7 g, 9.69
mmol) at 80°C for about 48 h and worked-up by pouring into ice-water and extracting
it with dichloromethane. The organic layer was washed with dil HCl (10%), satd aq
NaHCO3, brine, dried (Na2SO4), filtered and concentrated. Column chromatography
(ethyl acetate-hexane, 2:3, then 1:1) gave pure 14 (0.95 g, 49%) as a colourless syrup;
1
[a]D + 29° (c 2.35, CHCl3); H NMR d 1.62, 1.88, 1.93, 1.94 (s, 12H, 4 ꢁ CH3),
3.07–3.40 (m, 6H, H-1’a,b, H-6a,b and H-6’a,b), 3.90–4.19 (m, 3H, H-4, 5, 5’), 4.34 (t,
1H, J3’,4’ = J4’,5’ = 9.4 Hz, H-4’), 4.55 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.0 Hz, H-2),
5.01 (t, 1H, J3,4 = 10.0 Hz, H-3), 5.48 (d, 1H, H-1), 5.82 (d, 1H, H-3’) and 7.12–7.40
(m, 30H, Ar-H). 13C NMR d 171.6, 171.3, 169.5, 169.2 (4 ꢁ COCH3), 143.7, 143.6,
128.7, 127.8, 127.1 (Ar-C), 103.3 (C-2’), 88.6 (C-1), 87.2, 87.1 (CPh3), 81.8 (C-5’),
77.9 (C-3’), 73.0, 70.5, 69.6, 69.2 (C-2, 3, 4, 5), 64.9, 63.3, 62.7 (C-1’, 6, 6’), 55.9
(C-4’) and 20.7, 20.6, 20.4, 20.2 (4 ꢁ COCH3). HRMS-ESI (positive mode): calcd
for [M + Na] + 1035.3334:1037.3305. Found: 1035.3338:1037.3348.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-glucopyranoside (15). Treatment of 9 (1.65 g, 2.88 mmol) in MIBK
(35 mL) with AcOH (1.5 mL) as for 14 gave, after flash chromatography (ethyl
acetate-hexane, 2:3, then 1:1), pure 15 (1.78 g, 58%) as a colourless syrup; [a]D + 32°
1
(c 2.80, CHCl3); H NMR d 1.90, 1.93, 1.94, 2.04 (s, 12H, 4 ꢁ CH3), 2.98–3.41 (m,
6H, H-1’a,b, H-6a, b and H-6’a,b), 3.91–4.35 (m, 4H, H-4, 4’,5, 5’), 4.56 (dd, 1H,
J1,2 = 4.2 Hz, J2,3 = 10.0 Hz, H-2), 5.01 (t, 1H, J3,4 = 10.0 Hz, H-3), 5.50 (d, 1H,
H-1), 5.89 (d, 1H, J3’,4’ = 9.1 Hz, H-3’) and 7.12–7.41 (m, 30H, Ar-H). 13C NMR d
171.6, 171.3, 169.5, 169.2 (4 ꢁ COCH3), 143.7, 143.6, 128.7–127.1 (Ar-C), 103.5
(C-2’), 88.6 (C-1), 87.2, 87.0 (CPh3), 82.2 (C-5’), 78.3 (C-3’), 73.0, 70.5, 69.5, 69.2
(C-2, 3, 4, 5), 64.9, 63.4, 62.5 (C-1’, 6, 6’), 44.6 (C-4’) and 21.0, 20.8, 20.6, 20.4
(4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for [M+ Na] + 1079.2829:1081.2809.
Found: 1079.2835:1081.2835.
3-O-Acetyl-4-deoxy-4-iodo-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-glucopyranoside (16). A solution of 10 (1.57 g, 2.53 mmol) in MIBK (35
mL) was treated with AcOH (1.5 mL) as for 14 gave, after flash chromatography (ethyl
acetate-hexane, 2:3, then 1:1), pure 16 (1.56 g, 56%) as a colourless syrup; [a]D + 38° (c
1
2.40, CHCl3); H NMR d 2.02, 2.03, 2.04, 2.14 (s, 12H, 4 ꢁ CH3), 3.11–3.52 (m, 6H,
H-1’a,b, H-6a,b and H-6’a,b), 4.01–4.45 (m, 4H, H-4, 4’, 5, 5’), 4.66 (dd, 1H, J1,2
=
3.8 Hz, J2,3 = 10.0 Hz, H-2), 5.11 (t, 1H, J3,4 = 10.0 Hz, H-3), 5.62 (d, 1H, H-1),
6.01 (d, 1H, J3’,4’ = 9.7 Hz, H-3’) and 7.22–7.51 (m, 30H, Ar-H). 13C NMR d 171.6,
171.3, 169.5, 169.2 (4 ꢁ COCH3), 143.7, 143.6, 128.8–127.1 (Ar-C), 103.8 (C-2’),
88.6 (C-1), 87.1, 87.0 (CPh3), 83.7 (C-5’), 80.0 (C-3’), 73.0, 70.5, 69.6, 69.2 (C-2, 3,
4, 5), 64.9, 63.4, 62.3 (C-1’, 6, 6’), 21.0, 20.8, 20.5, 20.4 (4 ꢁ COCH3) and 18.6 (C-
4’). HRMS-ESI (positive mode): calcd for [M +Na] + 1127.2691. Found: 1127.2694.
3-O-Acetyl-4-chloro-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-galactopyranoside (17). A solution of 14 (0.85 g, 0.84 mmol) in dry
CH2Cl2-pyridine (15:1, 32.0 mL) at -78°C was treated with trifluoromethanesulfonic

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
195
anhydride (0.30 mL, 1.83 mmol). The mixture was stirred for 15 min at ꢂ 78°C, then
for about 2 h at 0°C. It was then diluted with dichloromethane and the organic solution
was washed successively with aq KHSO4 (10%), satd NaHCO3 and water, dried
(Na2SO4), filtered and concentrated. The residue was dissolved in DMF (50 mL) and
sodium nitrite (0.90 g, 13.0 mol) was added. The solution was then stirred at room
temperature overnight, concentrated, and the residue diluted with dichloromethane. The
filtered solution was again concentrated. Flash chromatography (ethyl acetate-hexane,
1:1) gave 17 (0.70 g, 82%): mp 108–110°C (ether-hexane); [a]D + 38° (c 2.02,
1
CHCl3); H NMR d 1.72, 1.95, 2.05, 2.14 (s, 12H, 4 ꢁ CH3), 3.15–3.21 (2 ꢁ d, 2H,
J1’a,1’b = 9.9 Hz, H-1’a,b), 3.36–3.53 (m, 2H, H-6’a,b), 4.01–4.33 (m, 5H, H-4, 5, 5’
and H-6a,b), 4.44 (t, 1H, J3’,4’ = J4’,5’ = 9.7 Hz, H-4’), 5.06 (dd, 1H, J2,3 = 10.9 Hz,
J3,4 = 2.6 Hz, H-3), 5.10 (dd, 1H, J1,2 = 3.4 Hz, H-2), 5.67 (d, 1H, H-1), 5.94 (d, 1H,
H-3’) and 7.22–7.52 (m, 30H, Ar-H). 13C NMR d 170.6, 169.9, 169.4, 169.0
(4 ꢁ COCH3), 143.5, 143.4, 128.5–126.9 (Ar-C), 102.9 (C-2’), 88.6 (C-1), 87.0, 86.9
(CPh3), 81.6 (C-5’), 77.4 (C-3’), 69.9, 68.0, 67.5, 66.6 (C-2, 3, 4, 5), 64.6, 63.0, 62.6
(C-1’, 6, 6’), 55.6 (C-4’) and 20.7, 20.5, 20.3, 20.2 (4 ꢁ COCH3). HRMS-ESI (positive
mode): calcd for [M + Na] + 1035.3334:1037.3305. Found: 1035.3354:1037.3347.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-galactopyranoside (18). Treatment of 15 (1.65 g, 1.56 mmol) with
trifluoromethanesulfonic anhydride (0.52 mL, 3.17 mmol) as above gave, after flash
chromatography (ethyl acetate-hexane, 1:1), 18 (1.31 g, 79%): mp 190–192°C (ether-
hexane); [a]D + 50° (c 0.98, CHCl3); 1H NMR d 1.71, 1.96, 2.05, 2.13 (s, 12H,
4 ꢁ CH3), 3.14–3.20 (2 ꢁ d, 2H, J1’a,1’b = 9.8 Hz, H-1’a,b), 3.38–3.51 (m, 2H, H-
6’a,b), 4.00–4.35 (m, 5H, H-4, 5, 5’ and H-6a,b), 4.41 (t, 1H, J3’,4’ = J4’,5’ = 9.8 Hz,
H-4’), 5.05–5.09 (m, 2H, H-2, 3), 5.69 (d, 1H, J1,2 = 2.7 Hz, H-1), 6.00 (d, 1H, H-3’)
and 7.21–7.51 (m, 30H, Ar-H). 13C NMR d 170.8, 170.0, 169.6, 169.2 (4 ꢁ COCH3),
143.7, 143.6, 128.8–127.1 (Ar-C), 103.3 (C-2’), 88.8 (C-1), 87.2, 87.1 (CPh3), 82.2
(C-5’), 78.1 (C-3’), 70.1, 68.2, 67.7, 66.8 (C-2, 3, 4, 5), 64.8, 63.3, 62.7 (C-1’, 6, 6’),
44.6 (C-4’) and 20.9, 20.5, 20.4 (4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for
[M + Na] + 1079.2829:1081.2809. Found: 1079.2847:1081.2843.
3-O-Acetyl-4-deoxy-4-iodo-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl- -D-galactopyranoside (19). Trifluoromethanesulfonic anhydride treatment of
16 (1.46 g, 1.32 mmol) as above gave, after flash chromatography (ethyl acetate-
hexane, 1:1), 19 (1.01 g, 69%): mp 200–202°C (ether-hexane); [a]D + 53° (c 1.15,
1
CHCl3); H NMR d 1.70, 1.97, 2.05, 2.13 (s, 12H, 4 ꢁ CH3), 3.12–3.19 (2 ꢁ d, 2H,
J1’a,1’b = 9.6 Hz, H-1’a,b), 3.41–3.51 (m, 2H, H-6’a,b), 3.98–4.38 (m, 6H, H-4, 4’, 5, 5’
and H-6a,b), 5.04–5.10 (m, 2H, H-2, 3), 5.70 (d, 1H, J1,2 = 2.7 Hz, H-1), 6.00 (d, 1H,
J3’,4’ = 9.8 Hz, H-3’) and 7.20–7.50 (m, 30H, Ar-H). 13C NMR d 170.8, 170.0, 169.5,
169.2 (4 ꢁ COCH3), 143.7, 143.6, 128.8–127.1 (Ar-C), 103.5 (C-2’), 88.8 (C-1), 87.1
(CPh3), 83.7 (C-5’), 79.7 (C-3’), 70.1, 68.1, 67.6, 66.8 (C-2, 3, 4, 5), 64.8, 63.1, 62.4
(C-1’, 6, 6’), 21.1, 20.9, 20.5, 20.3 (4 ꢁ COCH3) and 18.6 (C-4’). HRMS-ESI (positive
mode): calcd for [M + Na] + 1127.2691. Found: 1127.2690.
3-O-Acetyl-4-chloro-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-chloro-4-deoxy- -D-glucopyranoside (20). Compound 17 (1.13 g, 1.12

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mmol) was treated with trifluoromethanesulfonic anhydride (0.4 mL, 2.44 mmol) as
above. The crude syrup obtained after work-up in the usual manner was dissolved in
acetone (20 mL) and stirred with LiCl (0.30 g, 7.06 mmol) at room temperature for
ꢀ 12 h. When all starting material had reacted, the solvent was removed and the
residue taken up in dichloromethane and filtered. The filtrate was then washed with
satd aq NaHCO3 and brine; dried (Na2SO4), filtered and concentrated. Flash column
chromatography (ether-hexane, 1:1) gave 20 (0.85 g, 74%): mp 98–100°C (ether-
hexane); [a]D + 27° (c 1.77, CHCl3); 1H NMR d 1.63, 1.90, 1.96, 2.06 (s, 12H,
4 ꢁ CH3), 3.08–3.38 (m, 4H, H-1’a,b and H-6’a,b), 3.67 (t, 1H, J3,4 = J4,5 = 10.4
Hz, H-4), 4.05–4.23 (m, 4H, H-5, 5’ and H-6a,b), 4.34 (t, 1H, J3’,4’ = J4’,5’ = 9.1 Hz,
H-4’), 4.54 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.4 Hz, H-2), 5.26 (t, 1H, H-3), 5.55 (d,
1H, H-1), 5.83 (d, 1H, H-3’) and 7.14–7.40 (m, 30H, Ar-H). 13C NMR d 170.3,
169.5, 169.4, 169.1 (4 ꢁ COCH3), 143.6, 143.5, 128.7, 127.8, 127.1 (Ar-C), 103.5
(C-2’), 88.6 (C-1), 87.2, 87.1 (CPh3), 81.9 (C-5’), 78.0 (C-3’), 71.3, 70.3 (C-2, 3, 5),
64.8, 63.1, 62.5 (C-1’, 6, 6’), 55.8, 55.3 (C-4, 4’) and 20.7, 20.5, 20.3 (4 ꢁ COCH3).
HRMS-ESI (positive mode): calcd for [M + Na] + 1053.2996:1055.2966:1057.2936.
Found: 1053.2994:1055.2987:1057.3031.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-chloro-4-deoxy- -D-glucopyranoside (21). Compound 18 (0.47 g, 0.44
mmol) was treated as described for 20, gave after flash column chromatography
(ether-hexane, 1:1), 21 (0.39 g, 81%) as a colourless syrup; [a]D + 28° (c 1.28,
1
CHCl3); H NMR d 1.63, 1.92, 1.96, 2.07 (s, 12H, 4 ꢁ CH3), 3.08–3.20 (2 ꢁ d, 2H,
J1’a,1’b = 9.6 Hz, H-1’a,b), 3.27 (dd, 1H, J5’,6’a = 2.1 Hz, J6’a,6’b = 10.8 Hz, H-6’a),
3.37 (dd, 1H, J5’,6’b = 4.7 Hz, H-6’b), 3.68 (t, 1H, J3,4 = J4,5 = 10.1 Hz, H-4), 4.07–
4.35 (m, 5H, H-4’, 5, 5’ and H-6a,b), 4.54 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.1 Hz,
H-2), 5.26 (t, 1H, H-3), 5.57 (d, 1H, H-1), 5.90 (d, 1H, J3’,4’ = 9.1 Hz, H-3’) and
7.14–7.40 (m, 30H, Ar-H). 13C NMR d 170.3, 169.5, 169.4, 169.1 (4 ꢁ COCH3),
143.6, 143.5, 128.7–127.2 (Ar-C), 103.7 (C-2’), 88.6 (C-1), 87.3, 87.1 (CPh3), 82.4
(C-5’), 78.5 (C-3’), 71.3, 70.4 (C-2, 3, 5), 65.0, 63.2, 62.4 (C-1’, 6, 6’), 55.4 (C-4),
44.5 (C-4’) and 20.8, 20.6, 20.5, 20.3 (COCH3). HRMS-ESI (positive mode): calcd
for [M + Na] + 1097.2491:1099.2461:101.2441. Found: 1097.2481:1099.2462:
1101.2482.
3-O-Acetyl-4-deoxy-4-iodo-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-chloro-4-deoxy- -D-glucopyranoside (22). Treatment of 19 (0.70 g, 0.63
mmol) as above gave, after flash column chromatography (ether-hexane, 1:1), 22 (0.50
1
g, 70%): mp 93–95°C (ether-hexane); [a]D + 35° (c 0.57, CHCl3); H NMR d 1.62,
1.94, 1.96, 2.07 (s, 12H, 4 ꢁ CH3), 3.06–3.19 (2 ꢁ d, 2H, J1’a,1’b = 9.7 Hz, H-1’a,b),
3.29–3.41 (m, 2H, H-6’a,b), 3.69 (t, 1H, J3,4 = J4,5 = 10.1 Hz, H-4), 4.09–4.33 (m, 5H,
H-4’, 5, 5’ and H-6a,b), 4.54 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.1 Hz, H-2), 5.27 (t, 1H,
H-3), 5.60 (d, 1H, H-1), 5.92 (d, 1H, J3’,4’ = 9.7 Hz, H-3’) and 7.14–7.41 (m, 30H,
Ar-H). 13C NMR d 170.3, 169.5, 169.4, 169.1 (4 ꢁ COCH3), 143.6, 143.5, 128.8,
128.7, 127.8, 127.1 (Ar-C), 103.9 (C-2’), 88.6 (C-1), 87.2, 87.1 (CPh3), 83.8 (C-5’),
80.1 (C-3’), 71.3, 70.4, 70.3 (C-2, 3, 5), 65.0, 63.2, 62.2 (C-1’, 6, 6’), 55.4 (C-4), 21.0,
20.6, 20.5, 20.3 (4 ꢁ COCH3) and 18.4 (C-4’). HRMS-ESI (positive mode): calcd for
[M + Na] + 1145.2352:1147.2322. Found: 1145.2370:1147.2375.

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
197
3-O-Acetyl-4-chloro-4-deoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-
deoxy- -D-glucopyranoside (23). Treatment of 20 (0.82 g, 0.80 mmol) with ice-
cold CH2Cl2-AcOH (1:1, 20 mL) and conc HCl (0.15 mL) as above gave, after flash
chromatography (ethyl acetate-hexane, 2:1), 23 (0.32 g, 73%): mp 131–133°C (ether-
hexane); [a]D + 3.3° (c 2.02, CHCl3); 1H NMR d 2.06, 2.10, 2.12, 2.26 (s, 12H,
4 ꢁ CH3), 3.54–3.95 (m, 5H, H-4, H-1’a,b and H-6’a,b), 4.06–4.11 (m, 1H, H-5),
4.28–4.55 (m, 4H, H-4’, 5’ and H-6a,b), 4.80 (dd, 1H, J1,2 = 3.5 Hz, J2,3 = 10.1 Hz,
H-2), 5.43 (d, 1H, J3’,4’ = 9.4 Hz, H-3’), 5.50 (t, 1H, J3,4 = 10.1 Hz, H-3) and 5.66 (d,
1H, H-1). 13C NMR d 170.7, 170.5, 170.2, 169.5 (4 ꢁ COCH3), 103.9 (C-2’), 89.7 (C-
1), 83.3 (C-5’), 78.5 (C-3’), 71.0, 70.8, 70.5 (C-2, 3, 5), 64.2, 62.3, 59.2 (C-1’, 6, 6’),
54.9, 54.0 (C-4, 4’) and 20.6, 20.5, 20.4, 20.3 (4 ꢁ COCH3). HRMS-ESI (positive
mode): calcd for [M + Na] + 569.0805:571.0775:573.0745. Found: 569.0811:571.0789:
573.0771.
3-O-Acetyl-4-bromo-4-deoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-
deoxy- -D-glucopyranoside (24). Treatment of 21 (0.36 g, 0.33 mmol) as described
above gave, after flash chromatography (ethyl acetate-hexane, 2:1), 24 (0.15 g, 76%):
1
mp 114–115°C (ether-hexane); [a]D + 6.7° (c 1.12, CHCl3); H NMR d 1.98, 2.03,
2.06, 2.20 (s, 12H, 4 ꢁ CH3), 3.46–3.73 (m, 4H, H-1’a,b and H-6’a,b), 3.83 (t, 1H,
J3,4 = J4,5 = 10.2 Hz, H-4), 4.08–4.46 (m, 5H, H-4’, 5, 5’ and H-6a,b), 4.74 (dd, 1H,
J1,2 = 3.5 Hz, J2,3 = 10.2 Hz, H-2), 5.41 (d, 1H, J3’,4’ = 9.8 Hz, H-3’), 5.42 (t, 1H, H-
3) and 5.59 (d, 1H, H-1). 13C NMR d 170.6, 170.5, 170.2, 169.5 (4 ꢁ COCH3), 104.1
(C-2’), 89.7 (C-1), 83.7 (C-5’), 78.9 (C-3’), 71.0, 70.8, 70.5 (C-2, 3, 5), 64.2, 62.3, 59.1
(C-1’, 6, 6’), 54.9 (C-4), 42.6 (C-4’) and 20.7, 20.6, 20.5, 20.4 (4 ꢁ COCH3). HRMS-
ESI (positive mode): calcd for [M + Na] + 613.0300:615.0270:617.0250. Found:
613.0281:615.0268:617.0260.
3-O-Acetyl-4-deoxy-4-iodo- -D-fructofuranosyl 2,3,6-tri-O-acetyl-4-chloro-4-
deoxy- -D-glucopyranoside (25). Treatment of 22 (0.42 g, 0.37 mmol) as above
gave, after flash chromatography (ethyl acetate-hexane, 1:1), 25 (0.18 g, 75%) as a
1
colourless syrup; [a]D + 5.9° (c 0.76, CHCl3); H NMR d 1.99, 2.03, 2.06, 2.20 (s,
12H, 4 ꢁ CH3), 3.45–3.90 (m, 5H, H-4, H-1’a,b and H-6’a,b), 4.17–4.44 (m, 5H, H-
4’, 5, 5’ and H-6a,b), 4.75 (dd, 1H, J1,2 = 3.5 Hz, J2,3 = 10.2 Hz, H-2), 5.40 (d, 1H,
J3’,4’ = 10.4 Hz, H-3’), 5.41 (t, 1H, J3,4 = 10.2 Hz, H-3) and 5.58 (d, 1H, H-1). 13C
NMR d 170.7, 170.4, 170.1, 169.5 (4 ꢁ COCH3), 104.3 (C-2’), 89.5 (C-1), 85.4 (C-5’),
80.5 (C-3’), 71.1, 70.8, 70.5 (C-2, 3, 5), 64.3, 62.2, 58.7 (C-1’, 6, 6’), 54.9 (C-4), 20.7,
20.6, 20.5, 20.4 (4 ꢁ COCH3) and 16.2 (C-4’). HRMS-ESI (positive mode): calcd for
[M + Na] + 661.0161:663.0131. Found: 661.0164:663.0105.
3-O-Acetyl-1,4,6-trichloro-1,4,6-trideoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-
4-chloro-4-deoxy- -D-glucopyranoside (26). To a stirred solution of 23 (0.13 g, 0.25
mmol) and triphenylphosphine (0.57 g, 2.17 mmol) in pyridine (10 mL) at 0°C was
added CCl4 (0.35 mL, 2.27 mmol) drop-wise under an argon atmosphere. The reaction
mixture was stirred at 0°C for 0.5 h, then at room temperature for a further 0.5 h,
before being heated at about 85°C for 2 h. When TLC (ethyl acetate-hexane, 1:2)
showed that all the starting material had reacted, the reaction mixture was diluted with
dichloromethane and then washed with dil HCl (10%), satd aq NaHCO3 and brine;

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dried (Na2SO4), filtered and concentrated. Flash column chromatography (ethyl acetate-
hexane, 1:3) gave 26 (0.13 g, 92%) as a colourless syrup; [a]D + 18° (c 2.67, CHCl3);
1H NMR d 2.05, 2.10, 2.13, 2.24 (s, 12H, 4 ꢁ CH3), 3.61–3.89 (m, 5H, H-4, H-1’a,b
and H-6’a,b), 4.23–4.54 (m, 5H, H-4’, 5, 5’ and H-6a,b), 4.85 (dd, 1H, J1,2 = 3.8 Hz,
J2,3 = 10.1 Hz, H-2), 5.45 (t, 1H, J3,4 = 10.1 Hz, H-3), 5.64 (d, 1H, J3’,4’ = 8.4 Hz,
H-3’) and 5.66 (d, 1H, H-1). 13C NMR d 170.1, 169.6, 169.4, 169.3 (4 ꢁ COCH3),
102.7 (C-2’), 89.4 (C-1), 82.4 (C-5’), 78.1 (C-3’), 70.7, 70.6, 70.2 (C-2, 3, 5), 62.8 (C-
6), 56.1, 54.9 (C-4, 4’), 46.1, 42.3 (C-1’, 6’) and 20.5, 20.3, 20.2, 20.1 (COCH3).
HRMS-ESI (positive mode): calcd for [M + Na] + 605.0127:607.0097:609.0068.
Found: 605.0129:607.0110:609.0082.
3-O-Acetyl-4-bromo-1,6-dichloro-1,4,6-trideoxy- -D-fructofuranosyl 2,3,6-tri-
O-acetyl-4-chloro-4-deoxy- -D-glucopyranoside (27). Treatment of 24 (0.15 g,
0.26 mmol) as for 26, gave after column chromatography (ethyl acetate-hexane, 1:3)
1
27 (0.14 g, 88%) as a colourless syrup; [a]D + 22° (c 1.62, CHCl3); H NMR d 1.99,
2.03, 2.07, 2.17 (s, 12H, 4 ꢁ CH3), 3.53–3.84 (m, 5H, H-4, H-1’a,b and H-6’a,b),
4.16–4.45 (m, 5H, H-4’, 5, 5’ and H-6a,b), 4.78 (dd, 1H, J1,2 = 3.5 Hz, J2,3 = 10.1
Hz, H-2), 5.39 (t, 1H, J3,4 = 10.1 Hz, H-3), 5.60 (d, 1H, H-1) and 5.64 (d, 1H,
J3’,4’ = 9.1 Hz, H-3’). 13C NMR d 170.3, 169.8, 169.6, 169.5 (4 ꢁ COCH3), 103.1
(C-2’), 89.7 (C-1), 82.8 (C-5’), 78.7 (C-3’), 70.9, 70.8, 70.5 (C-2, 3, 5), 63.0 (C-6), 55.1
(C-4), 44.2 (C-4’), 46.3, 42.4 (C-1’, 6’) and 20.8, 20.6, 20.5, 20.3 (4 x COCH3). HRMS-
ESI (positive mode): calcd for [M + Na] + 648.9622:650.9602:652.9572:654.9543.
Found: 648.9632:650.9601:652.9581:654.9558.
3-O-Acetyl-1,6-dichloro-1,4,6-trideoxy-4-iodo- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-chloro-4-deoxy- -D-glucopyranoside (28). Compound 25 (0.16 g, 0.24
mmol) was treated with triphenylphosphine (0.55 g, 2.10 mmol) and CCl4 (0.32 mL,
2.08 mmol) as described for 26 gave, after column chromatography (ethyl acetate-
hexane, 1:3), 28 (0.15 g, 89%): mp 62–64°C (ether-hexane); [a]D + 31° (c 0.23,
1
CHCl3); H NMR d 1.98, 2.03, 2.08, 2.17 (s, 12H, 4 ꢁ CH3), 3.51–3.86 (m, 5H, H-4,
H-1’a,b and H-6’a,b), 4.16–4.45 (m, 5H, H-4’, 5, 5’ and H-6a,b), 4.78 (dd, 1H,
J1,2 = 3.5 Hz, J2,3 = 10.1 Hz, H-2), 5.38 (t, 1H, J3,4 = 10.1 Hz, H-3) and 5.59–5.64
(m, 2H, H-1, 3’). 13C NMR d 170.3, 169.7, 169.6, 169.5 (4 ꢁ COCH3), 103.3 (C-2’),
89.7 (C-1), 84.2 (C-5’), 80.3 (C-3’), 70.8, 70.5 (C-2, 3, 5), 63.0 (C-6), 55.1 (C-4), 46.2,
42.3 (C-1’, 6’), 20.9, 20.6, 20.5, 20.3 (4 ꢁ COCH3) and 17.3 (C-4’). HRMS-ESI
(positive mode): calcd for [M + Na] + 696.9483: 698.9453. Found: 696.9475:
698.9453.
1,4,6-Trichloro-1,4,6-trideoxy- -D-fructofuranosyl 4-chloro-4-deoxy- -D-gluco-
pyranoside (29). A solution of 26 (0.13 g, 0.22 mmol) in methanol was treated
with methanolic NaOMe at pH ꢀ 9 for 1 h. The reaction was monitored by TLC
(MeOH-CHCl3, 3:17). The mixture was neutralized using Amberlite IR120 (H + ) ion
exchange resin, filtered and concentrated to afford 29 (0.089 g, 94%) as a colourless
syrup; [a]D + 41° (c 0.25, H2O); 1H NMR (D2O) d 4.14 (dd, 1H, J1,2 = 3.8 Hz,
J2,3 = 9.7 Hz, H-2), 4.29–4.51 (m, 8H, H-1’a,b, H-3, 4, H-6a,b and H-6’a,b), 4.64–
4.72 (m, 2H, H-4’,5), 4.83–4.90 (m, 1H, H-5’), 5.09 (d, 1H, J3’,4’ = 9.7 Hz, H-3’) and
6.03 (d, 1H, H-1). 13C NMR (D2O) d 104.1 (C-2’), 93.6 (C-1), 82.5 (C-5’), 78.3 (C-3’),

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
199
73.6, 73.1, 72.1 (C-2, 3, 5), 61.1 (C-6), 59.5, 58.5 (C-4, 4’) and 44.5, 43.9 (C-1’, 6’).
HRMS-ESI (positive mode): calcd for [M + Na] + 436.9704:438.9675:
440.9645:442.9616:444.9586. Found: 436.9709:438.9687:440.9648:442.9594:
444.9583.
4-Bromo-1,6-dichloro-1,4,6-trideoxy- -D-fructofuranosyl 4-chloro-4-deoxy- -D-
glucopyranoside (30). Treatment of 27 (0.11 g, 0.17mmol) as for 29 gave 30 as a
1
colourless syrup (0.072 g, 91%); [a]D + 40° (c 0.27, H2O); H NMR (D2O) d 4.12 (dd,
1H, J1,2 = 3.8 Hz, J2,3 = 9.8 Hz, H-2), 4.27–4.52 (m, 8H, H-1’a,b, H-3, 4, H-6a,b and
H-6’a,b), 4.61–4.68 (m, 2H, H-4’, 5), 4.92–4.99 (m, 1H, H-5’), 5.13 (d, 1H,
J3’,4’ = 10.1 Hz, H-3’) and 6.02 (d, 1H, H-1). 13C NMR (D2O) d 104.1 (C-2’), 93.6 (C-
1), 82.9 (C-5’), 78.7 (C-3’), 73.6, 73.1, 72.1 (C-2, 3, 5), 61.1 (C-6), 58.5 (C-4), 48.3 (C-
4’) and 44.4, 43.9 (C-1’, 6’). HRMS-ESI (positive mode): calcd for [M + Na] +
480.9199:482.9179:484.9140:486.9120: 488.9090. Found: 480.9191:482.9180:
484.9138:486.9143: 488.9118.
1,6-Dichloro-1,4,6-trideoxy-4-iodo- -D-fructofuranosyl 4-chloro-4-deoxy- -D-
glucopyranoside (31). Deacetylation of 28 (0.14 g, 0.21mmol) as for 29, gave 31
1
as a colourless syrup (0.092, 88%); [a]D + 32° (c 0.32, H2O); H NMR (D2O) d 4.13
(dd, 1H, J1,2 = 3.8 Hz, J2,3 = 9.8 Hz, H-2), 4.28–4.68 (m, 10H, H-1’a,b, H-3, 4, 4’, 5,
H-6a,b and H-6’a,b), 5.00–5.06 (m, 1H, H-5’), 5.12 (d, 1H, J3’,4’ = 10.4 Hz, H-3’) and
6.03 (d, 1H, H-1). 13C NMR (D2O) d 104.0 (C-2’), 93.5 (C-1), 84.4 (C-5’), 80.3 (C-3’),
73.6, 73.1, 72.1 (C-2, 3, 5), 61.1 (C-6), 58.5 (C-4), 44.3, 43.9 (C-1’, 6’) and 22.2 (C-4’).
HRMS-ESI (positive mode): calcd for [M + Na] + 528.9060:530.9031:532.9001.
Found: 528.9088:530.9046:532.8986.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-deoxy-4-fluoro- -D-galactopyranoside (32). A solution of 15 (0.68 g,
0.64 mmol) in CH2Cl2-pyridine (15:1, 32 mL) at ꢂ 78°C was treated with tri-
fluoromethanesulfonic anhydride (0.20 mL, 1.22 mmol) as described above, and
worked-up in the usual manner. To a thoroughly dried crude product in CH2Cl2 (20
mL) was added TASF (0.72 g, 2.61 mmol). The mixture was heated to about 45 °C
for 0.5 h when TLC (ether-hexane, 1:1) indicated that all starting material had been
consumed. The reaction mixture was washed successively with satd NaHCO3 and
brine; dried (Na2SO4), filtered and concentrated, and chromatographed (ether-hexane,
1:1) to give 32 (0.49 g, 72%): mp 94–96°C (ether-hexane); [a]D + 36° (c 0.82,
1
CHCl3); H NMR d 2.21, 2.45, 2.56, 2.61 (s, 12H, 4 ꢁ CH3), 3.60–4.00 (m, 4H,
H-1’a,b and H-6’a,b), 4.54–4.83 (m, 4H, H-5, 5’ and H-6a,b), 4.90 (t, 1H,
J3’,4’ = J4’,5’ = 10.0 Hz, H-4’), 5.35 (dd, 1H, J3,4 = 1.7 Hz, J4,F 50.9 Hz, H-4),
5.46–5.61 (m, 2H, H-2, 3), 6.24 (d, 1H, J1,2 = 3.1 Hz, H-1), 6.49 (d, 1H, H-3’) and
7.71–8.00 (m, 30H, Ar-H). 13C NMR d 170.3, 170.2, 169.2, 169.0 (4 ꢁ COCH3),
143.7, 143.6, 128.7–127.1 (Ar-C), 103.4 (C-2’), 88.6 (C-1), 87.2 (CPh3), 86.9
(J4,F = 185.2 Hz, C-4), 82.2 (C-5’), 78.1 (C-3’), 68.2 (J3,F = 17.1 Hz, C-3), 67.4
(J5,F = 18.2 Hz, C-5), 66.5 (C-2), 64.8, 62.3, 62.2 (C-1’, 6, 6’), 44.4 (C-4’) and
20.7, 20.5, 20.4 (COCH3). 19F NMR d -143.9 (dt, JF,H-3 = 30.5 Hz, JF,H-4 = 50.9
Hz, JF,H-5 = 15.3 Hz). HRMS-ESI (positive mode): calcd for [M + Na] +
1081.2786:1083.2766. Found: 1081.2770:1083.2788.

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3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-fructofuranosyl 2,3,6-tri-O-
acetyl-4-deoxy-4-iodo- -D-galactopyranoside (33). Compound 15 (0.89 g, 0.84
mmol) was triflated as above and treated with KI (0.45 g, 2.71 mmol) in acetone
(25 mL) at room temperature for ꢀ 12 h, to give, after flash column chromatography
(ether-hexane, 1:1), 33 (0.70 g, 71%): mp 99–101°C (ether-hexane); [a]D + 50°
(c 1.34, CHCl3); 1H NMR d 1.59, 1.85, 1.98, 2.03 (s, 12H, 4 ꢁ CH3), 3.01–3.09
(2 ꢁ d, 2H, J1’a,1’b = 9.75 Hz, H-1’a,b), 3.30–3.41 (m, 2H, H-6’a,b), 3.53–3.97 (m,
3H, H-5 and H-6a,b), 4.15–4.32 (m, 3H, H-3, 4’, 5), 4.56 (t, 1H, J3,4 = J4,5 = 2.8 Hz,
H-4), 4.97 (dd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.4 Hz, H-2), 5.48 (d, 1H, H-1), 5.91 (d,
1H, J3’,4’ = 9.7 Hz, H-3’) and 7.14–7.41 (m, 30H, Ar-H). 13C NMR d 170.1, 169.9,
169.2, 169.0 (4°COCH3), 143.6, 143.5, 128.6–127.0 (Ar-C), 103.4 (C-2’), 88.7 (C-1),
87.1 87.0 (CPh3), 82.3 (C-5’), 77.8 (C-3’), 69.1, 68.2, 66.6 (C-2, 3, 5), 68.5, 64.5,
62.8 (C-1’, 6, 6’), 44.4 (C-4’), 35.1 (C-4) and 20.8, 20.7, 20.4, 20.3 (4 ꢁ COCH3).
HRMS-ESI (positive mode): calcd for [M + Na] + 1189.1847:1191.1827. Found: 1189.
1883:1191.1872.
3-O-Acetyl-4-bromo-4-deoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-4-deoxy-4-
fluoro- -D-galactopyranoside (34). Treatment of 32 (0.38 g, 0.36 mmol) with ice-
cold CH2Cl2-AcOH (1:1, 20 mL) and conc HCl (0.07 mL) as described above, gave
after flash chromatography (ethyl acetate-hexane, 1:1), 34 (0.17 g, 82%) as a colourless
syrup; [a]D + 27° (c 1.01, CHCl3); 1H NMR d 2.08, 2.11, 2.13, 2.23 (s, 12H,
4 ꢁ CH3), 3.54–3.97 (m, 4H, H-1’a,b and H-6’a,b), 4.11–4.41 (m, 4H, H-5, 5’ and H-
6a,b), 4.49 (t, 1H, J3’,4’ = J4’,5’ = 10.0 Hz, H-4’), 4.93 (dd, 1H, J3,4 = 2.1 Hz, J4,F 50.9
Hz, H-4), 5.17–5.34 (m, 2H, H-2, 3), 5.47 (d, 1H, H-3’) and 5.73 (d, 1H, J1,2 = 2.8
Hz, H-1). 13C NMR d 170.5, 170.4, 170.2, 170.1 (4 ꢁ COCH3), 103.8 (C-2’), 89.8
(C-1), 86.8 (J4,F = 185.2 Hz, C-4), 83.4 (C-5’), 78.6 (C-3’), 67.7 (J3,F = 18.2 Hz,
C-3), 67.3 (J5,F = 17.6 Hz, C-5), 67.1 (C-2), 63.8, 59.3 (C-1’, 6’), 61.5 (J6,F = 6.5
Hz, C-6), 42.6 (C-4’) and 20.6, 20.6, 20.6, 20.3 (4 ꢁ COCH3). 19F NMR d -143.27
(dt, JF,H-3 = 30.5 Hz, JF,H-4 = 53.4 Hz, JF,H-5 = 22.9 Hz). HRMS-ESI (positive
mode): calcd for [M + Na] + 597.0595:599.0575. Found: 597.0622:599.0578.
3-O-Acetyl-4-bromo-4-deoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-4-deoxy-4-
iodo- -D-galactopyranoside (35). Treatment of 33 (0.65 g, 0.56 mmol) as described
above, gave after flash chromatography (ethyl acetate-hexane, 1:1), 35 (0.32 g, 85%) as
1
a colourless syrup; [a]D + 37° (c 1.05, CHCl3); H NMR d 2.09, 2.11, 2.13, 2.23 (s,
12H, 4 ꢁ CH3), 3.53–3.81 (m, 4H, H-1’a,b and H-6’a,b), 3.92–4.32 (m, 4H, H-5,
5’and H-6a,b), 4.46–4.53 (m, 2H, H-3, 4’), 4.70 (dd, 1H, J3,4 = 4.0 Hz, J4,5 = 1.5 Hz,
H-4), 5.22 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.6 Hz, H-2), 5.47 (d, 1H, J3’,4’ = 9.7 Hz,
H-3’) and 5.67 (d, 1H,, H-1). 13C NMR d 170.4, 170.3, 170.2, 169.9 (4 ꢁ COCH3),
103.8 (C-2’), 89.8 (C-1), 83.5 (C-5’), 78.4 (C-3’), 69.8, 67.5, 67.0 (C-2, 3, 5), 67.9,
64.0, 59.6 (C-1’, 6, 6’), 42.6 (C-4’), 34.9 (C-4) and 20.8, 20.7, 20.6, 20.4
(4 ꢁ COCH3 ). HRMS-ESI (positive mode): calcd for [M + Na] +
704.9656:706.9636. Found: 704.9667:706.9656.
3-O-Acetyl-1,4,6-tribromo-1,4,6-trideoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-
4-deoxy-4-fluoro- -D-galactopyranoside (36). Compound 34 (0.18 g, 0.31 mmol)
was triflated as described above and treated with LiBr (0.60 g) in acetone (20 mL) at

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
201
45°C overnight. Column chromatography (ether-hexane, 1:1) gave 36 (0.13 g, 59%) as
1
a colourless syrup; [a]D + 46° (c 0.94, CHCl3); H NMR d 2.02, 2.05, 2.05, 2.13 (s,
12H, 4 ꢁ CH3), 3.46 (d, 1H, J1’a,1’b = 11.0 Hz, H-1’a), 3.54 (d, 1H, H-1’b), 3.56 (dd,
1H, J5’6’a = 6.3 Hz, J6’a,6’b = 11.5 Hz, H-6’a), 3.64 (dd, 1H, J5’,6’b = 3.8 Hz, H-6’b),
4.13–4.38 (m, 5H, H-4’, 5, 5’, 6a,b), 4.85 (dd, 1H, J3,4 = 2.1 Hz, J4,F = 49.5 Hz, H-4),
5.10-5.23 (m, 2H, H-2, 3), 5.63 (d, 1H, J1,2 = 3.1 Hz, H-1) and 5.69 (d, 1H,
J3’,4’ = 9.4 Hz, H-3’). 13C NMR d 170.3, 170.2, 169.7, 169.5 (4 ꢁ COCH3), 102.4
(C-2’), 90.2 (C-1), 86.9 (J4,F = 185.2 Hz, C-4), 82.5 (C-5’), 79.1 (C-3’), 68.0
(J3,F = 18.2 Hz, C-3), 67.6 (J5,F = 17.6 Hz, C-5), 66.7 (C-2), 62.3 (J6,F = 6.5 Hz,
C-6), 45.7 (C-4’), 34.0, 30.0 (C-1’,6’) and 20.8, 20.7, 20.6, 20.3 (4 ꢁ COCH3). 19F
NMR d -142.9 (dt, JF,H-3 = 30.5 Hz, JF,H-4 = 53.4 Hz, JF,H-5 = 30.5 Hz). HRMS-
ESI (positive mode): calcd for [M + Na] + 720.8907:722.8887:724.8867:726.8847.
Found: 720.8888:722.8891:724.8855:726.8861.
3-O-Acetyl-1,4,6-tribromo-1,4,6-trideoxy- -D-fructofuranosyl 2,3,6-tri-O-acetyl-
4-deoxy-4-iodo- -D-galactopyranoside (37). Treatment of 35 (0.34 g, 0.50 mmol) as
for 36 gave, after column chromatography (ether-hexane, 1:1), 37 (0.21 g, 52%) as a
1
colourless syrup; [a]D + 54° (c 1.76, CHCl3); H NMR d 2.02, 2.06, 2.06, 2.13 (s,
12H, 4 ꢁ CH3), 3.43 (d, 1H, J1’a,1’b = 11.0 Hz, H-1’a), 3.52 (d, 1H, H-1’b), 3.54 (dd,
1H, J5’,6’a = 6.3 Hz, J6’a,6’b = 11.1 Hz, H-6’a), 3.63 (dd, 1H, J5’,6’b = 3.8 Hz, H-6’b),
3.74–3.78 (m, 1H, H-5), 4.06–4.08 (m, 2H, H-6a,b), 4.21 (t, 1H, J3’,4’ = J4’,5’ = 9.4
Hz, H-4’), 4.32–4.43 (m, 2H, H-3, 5’), 4.63 (dd, 1H, J3,4 = 3.8 J4,5 = 1.4 Hz, H-4),
5.19 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.4 Hz, H-2), 5.55 (d, 1H, H-1), 5.68 (d, 1H,
H-3’). 13C NMR d 170.1, 169.8, 169.6, 169.4 (4 ꢁ COCH3), 102.4 (C-2’), 90.2 (C-1),
82.6 (C-5’), 78.9 (C-3’), 68.7 (C-6), 69.3, 67.7, 67.3 (C-2, 3, 5), 45.7 (C-4’), 34.2
(C-4), 33.8, 29.9 (C-1’, 6’) and 20.9, 20.8, 20.7, 20.3 (4 ꢁ COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 828.7968:830.7948:832.7928:834.7908. Found:
828.7962:830.7951:832.7937:834.7944.
1,4,6-Tribromo-1,4,6-trideoxy- -D-fructofuranosyl 4-deoxy-4-fluoro- -D-galac-
topyranoside (38). Deacetylation of 36 (0.10 g, 0.14 mmol) in methanolic-NaOMe
(ꢀ pH 9) at 0°C gave 38 (0.065 g, 86%) as a colourless syrup; [a]D + 45° (c 2.01,
MeOH); 1H NMR (D2O) d 4.17–4.56 (m, 8H, H-2, 3, 1’a,b, 6’a,b and 6a,b), 4.60 (t, 1H,
J3’,4’ = J4’,5’ = 10.0 Hz, H-4’), 4.75 (m, 1H, JF,5 = 31.0 Hz, H-5), 4.94–5.01 (m, 1H,
H-5’), 5.19 (d, 1H, 10.0 Hz, H-3’), 5.42 (d, 1H, J3,4 = 2.1 Hz, JF,4 = 50.9 Hz, H-4),
6.05 (d, 1H, J1,2 = 3.8 Hz, H-1). 13C NMR (D2O) d 103.5 (C-2’), 93.5 (C-1), 90.9
(JF,4 = 177.6 Hz, C-4), 82.8 (C-5’), 79.4 (C-3’), 71.3 (JF,3 = 17.6 Hz, C-3), 68.4
(JF,5 = 14.7 Hz, C-5), 68.3 (JF,2 = 2.9 Hz, C-2), 60.6 (JF,6 = 5.9 Hz, C-6), 49.6
(C-4’), 32.1, 32.0 (C-1’, 6’). 19F NMR (D2O) d -144.3 (dt, JF,H-4 = 45.8 Hz, JF,H-
= 30.5 Hz, JF,H-5 = 30.5 Hz). HRMS-ESI (positive mode): calcd for [M + Na] +
3
552.8485:554.8465:556.8445:558.8424. Found: 552.8476:554.8474:556.8457:558.8439.
1,4,6-Tribromo-1,4,6-trideoxy- -D-fructofuranosyl 4-deoxy-4-iodo- -D-galacto-
pyranoside (39). Compound 37 (0.18 g, 0.22 mmol) was treated with methanolic-
NaOMe ( ꢀ pH 9) at 0°C to give 39 (0.11 g, 77%) as a colourless syrup; [a]D + 49° (c
1
0.96, MeOH); H NMR (D2O) d 3.79 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 10.0 Hz, H-2),
4.09–4.34 (m, 7H, H-1’a,b, 5, 6a,b, 6’a,b), 4.40 (dd, 1H, J3,4 = 4.0 Hz, H-3), 4.67 (t,

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1H, J3’,4’ = J4’,5’ = 9.7 Hz, H-4’), 4.94–5.01 (m, 1H, H-5’), 5.13 (d, 1H, H-4), 5.18 (d,
1H, H-3’) and 5.97 (d, 1H, H-1). 13C NMR (D2O) d 103.5 (C-2’), 93.4 (C-1), 83.0 (C-
5’), 79.2 (C-3’), 71.3, 71.1 (C-2, 3), 68.0 (C-5), 66.8 (C-6), 49.5 (C-4’), 42.6 (C-4) and
32.3, 32.2 (C-1’, 6’). HRMS-ESI (positive mode): calcd for [M + Na] +
660.7545:662.7525:664.7505:666.7485. Found: 660.7563:662.7525:664.7496:666.7510.
3-O-Acetyl-4-bromo-4-deoxy-1,6-di-O-trityl- -D-tagatofuranosyl 2,3,4-tri-O-
acetyl-6-O-trityl- -D-glucopyranoside (41). To a solution of 1,6-di-O-trityl-b-D-
fructofuranosyl 6-O-trityl-a-D-glucopyranoside (7.35 g, 6.88 mmol) in toluene (150 mL)
was added n-dibutyltin oxide (1.71 g, 6.87 mmol). The reaction mixture was heated
under azeotropic distillation overnight. The reaction mixture was concentrated and dried
under vacuum for 2 h. The crude product was dissolved in CH2Cl2 (100 mL) and
pyridine (7 mL) and cooled to ꢀ ꢂ 60°C. Trifluoromethanesulfonic anhydride (2.2
mL, 13.4 mmol) was added drop-wise to the stirred mixture under argon atmosphere.
The temperature was then allowed to rise to 0°C, stirred for ꢀ 10 min, worked-up in
the usual manner, and chromatographed (ethyl acetate-hexane, 1:1).
A solution of the triflate in acetone (50 mL) was stirred with LiBr (0.44 g) at
room temperature overnight, and worked-up in the usual manner. The crude syrupy
product was then acetylated (acetic anhydride/pyridine). Column chromatography
(ethyl acetate-hexane, 1:2) gave 41 as a yellowish syrup (2.2 g, 25%); [a]D + 72°
(c 1.20, CHCl3); 1H NMR d 1.54, 1.71, 1.89, (s, 12H, 4 ꢁ CH3), 2.69 (dd, 1H,
J5,6a = 2.0 Hz, J6a,6b = 10.0 Hz, H-6a), 3.18 (dd, 1H, J5,6b = 2.0 Hz, H-6b), 3.25
(s, 2H, H-1’a,b), 3.32 (dd, 1H, J5’6’a = 4.9 Hz, J6’a,6’b = 10.1 Hz, H-6’a), 3.40 (dd,
1H, J5’6’b = 6.6 Hz, H-6’b), 4.01–4.04 (m, 1H, H-5), 4.19–4.25 (m, 1H, H-5’), 4.52
(t, 1H, J3’,4’ = J4’,5’ = 5.0 Hz, H-4’), 4.80 (dd, 1H, J1,2 = 3.5 Hz, J2,3 = 9.7 Hz, H-
2), 5.19–5.30 (m, 3H, H-3, 3’, 4), 5.44 ( d, 1H, H-1) and 7.08–7.33 (m, 45H, Ar-
H). 13C NMR d170.3, 169.9, 169.8, 169.0 (4 ꢁ COCH3), 143.7, 143.2, 128.7, 128.0,
127.8, 127.3, 126.8 (Ar-C), 104.7 (C-2’), 90.4 (C-1), 87.4, 87.1, 86.1 (CPh3), 78.7
(C-5’), 73.0 (C-3’), 70.8 (C-3), 70.6 (C-2), 69.4 (C-5), 68.6 (C-4), 65.4 (C-6’), 64.7
(C-1’), 60.7 (C-6), 50.0 (C-4’) and 20.8, 20.6, 20.5, 20.4 (4 x COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 1321.3925:1323.3905. Found: 1321.3900:
1323.3927.
3-O-Acetyl-4-deoxy-4-iodo-1,6-di-O-trityl- -D-tagatofuranosyl 2,3,4-tri-O-
acetyl-6-O-trityl- -D-glucopyranoside (42). The 4’-O-triflate of 40 as prepared for
41 was treated with KI (1.0 g) in acetone (50 mL) at room temperature for ꢀ 12 h, and
then acetylated to give 42 (2.4 g, 26%): mp 120–122 °C (methanol); [a]D + 57° (c
1
0.78, CHCl3); H NMR d 1.47, 1.83, 1.90, 1.94 (s, 12H, 4 ꢁ CH3), 2.69 (dd, 1H,
J5,6a = 2.1 Hz, J6a,6b = 10.1 Hz, H-6a), 3.17–3.46 (m, 5H, H-1’a,b, H-6’a,b and
H-6a,b), 3.80–3.86 (m, 1H, H-5’), 4.06–4.09 (m, 1H, H-5), 4.34 (t, 1H,
J3’,4’ = J4’,5’ = 5.6 Hz, H-4’), 4.81 (dd, 1H, J1,2 = 3.8 Hz, J2,3 = 9.8 Hz, H-2), 4.95
(d, 1H, H-3’), 5,20–5.34 (m, 2H, H-3, 4), 5.39 (d, 1H, H-1) and 7.05–7.37 (m, 45H,
Ar-H). 13C NMR d170.3, 170.0, 169.5, 168.9 (4 ꢁ COCH3), 143.8, 143.7, 128.8,
128.6, 127.7, 127.0, 126.8 (Ar-C), 105.1 (C-2’), 91.0 (C-1), 87.5, 87.0, 86.0 (CPh3),
78.4 (C-5’), 73.5 (C-3’), 70.7, 70.6 (C-2, 3), 69.6 (C-5), 68.8 (C-6’), 68.4 (C-4), 63.8
(C-1’), 60.5 (C-6), 26.4 (C-4’) and 20.8, 20.7, 20.5, 20.4 (4 ꢁ COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 1369.3786. Found: 1369.3812.

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
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3-O-Acetyl-4-bromo-4-deoxy- -D-tagatofuranosyl 2,3,4-tri-O-acetyl- -D-gluco-
pyranoside (43). Detritylation of 41 (2.62 g, 2.02 mmol) as described above
afforded, after chromatography (ethyl acetate-hexane, 5:1), 43 as a colourless syrup
1
(0.71 g, 61%); [a]D + 72° (c 0.66, CHCl3); H NMR d 2.01, 2.06, 2.07, 2.27 (s, 12H,
4 ꢁ CH3), 3.56–3.93 (m, 6H, H-1’a,b, H-6a,b and H-6’a,b), 4.18–4.23 (m, 1H, H-5),
4.36–4.42 (m, 1H, H-5’), 4.67 (t, 1H, J3’,4’ = J4’,5’ = 6.0 Hz, H-4’), 4.86 (dd, 1H,
J1,2 = 3.5 Hz, J2,3 = 10.0 Hz, H-2), 5.00 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.39 (d,
1H, H-3’), 5.46 (t, 1H, H-3), 5.64 (d, 1H, H-1). 13C NMR d 170.4, 170.2, 170.0, 169.9
(4 ꢁ COCH3), 105.7 (C-2’), 90.5 (C-1), 78.7 (C-5’), 72.9 (C-3’), 71.5, 70.6, 69.4, 68.7
(C-2, 3, 4, 5), 64.1, 63.7, 61.2 (C-6, 1’, 6’), 45.8 (C-4’) and 20.6, 20.5 (4 ꢁ COCH3).
HRMS-ESI (positive mode): calcd for [M + Na] + 595.0638:597.0618. Found:
595.0645:597.0624.
3-O-Acetyl-4-deoxy-4-iodo- -D-tagatofuranosyl 2,3,4-tri-O-acetyl- -D-glucopy-
ranoside (44). Detritylation of 42 (2.27 g, 1.69 mmol) as described above, gave after
flash column chromatography (ethyl acetate-hexane, 5:1), 44 as a yellowish syrup (0.73 g,
70%); [a]D + 71° (c 1.53, CHCl3); 1H NMR d 1.95, 1.98, 2.01, 2.21 (s, 12H, 4 ꢁ CH3),
3.40–3.59 (m, 2H, H-6a,b), 3.64–3.79 (m, 4H, H-1’a,b and H-6’a,b), 4.07–4.10 (m, 1H,
H-5), 4.16–4.22 (m, 1H, H-5’), 4.55 (t, 1H, J3’,4’ = J4’,5’ = 6.6 Hz, H-4’), 4.78 (dd, 1H,
J1,2 = 3.5 Hz, J2,3 = 10.0 Hz, H-2), 4.96 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 5.17 (d, 1H,
H-3’), 5.36 (t, 1H, H-3), 5.58 (d, 1H, H-1). 13C NMR d170.6, 170.0, 169.9, 169.6
(4 ꢁ COCH3), 105.7 (C-2’), 90.7 (C-1), 81.7 (C-5’), 73.8 (C-3’), 71.6, 70.4, 69.3,
68.6 (C-2, 3, 4, 5), 66.6, 63.8, 61.0 (C-1’, 6, 6’), 20.6, 20.5 (4 ꢁ COCH3) and 20.3
(C-4’). HRMS-ESI (positive mode): calcd for [M + Na] + 643.0500. Found: 643.0499.
3-O-Acetyl-4-bromo-4-deoxy- -D-tagatofuranosyl 2,3,6-tri-O-acetyl- -D-gluco-
pyranoside (45). Compound 43 (0.46 g, 0.80 mmol) in MIBK (20 mL) was treated
with AcOH (0.45 mL) as for 14, to give, after flash column chromatography (ethyl
acetate-hexane, 5:1), 45 as a colourless syrup (0.30 g, 65%); [a]D + 60° (c 0.72,
1
CHCl3); H NMR d 2.02, 2.03, 2.07, 2.17 (s, 12H, 4 ꢁ CH3), 3.42–3.56 (m, 3H, H-
1’a,b and H-4), 3.73–3.86 (m, 2H, H-6’a,b), 4.13–4.18 (m, 1H, H-5), 4.26 (dd, 1H,
J5,6a = 2.1 Hz, J6a,6b = 12.0 Hz, H-6a), 4.31–4.36 (m, 1H, H-5’), 4.39 (dd, 1H,
J5,6b = 3.8 Hz, H-6b), 4.63 (t, 1H, J3’,4’ = J4’,5’ = 6.0 Hz, H-4’), 4.76 (dd, 1H,
J1,2 = 3.5 Hz, J2,3 = 10.0 Hz, H-2), 5.20 (t, 1H, J3,4 = 10.0 Hz, H-3), 5.32 (d, 1H,
H-3’), 5.48 (d, 1H, H-1). 13C NMR d 171.8, 171.5, 170.6, 169.9 (4 ꢁ COCH3), 105.6
(C-2’), 90.6 (C-1), 81.2 (C-5’), 72.7 (C-3’), 72.2, 71.4, 70.4, 68.8 (C-2, 3, 4, 5), 64.2,
64.1, 62.7 (C-6, 1’, 6’), 46.1 (C-4’), 20.8, 20.7, 20.7 (4 ꢁ COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 595.0638:597.0618. Found 595.0639:597.0629.
3-O-Acetyl-4-deoxy-4-iodo- -D-tagatofuranosyl 2,3,6-tri-O-acetyl- -D-glucopy-
ranoside (46). Compound 44 (0.48 g, 0.774 mmol) was treated as for 14 to give,
after chromatography (ethyl acetate-hexane, 5:1), 45 (0.38 g, 79%) as colourless syrup;
1
[a]D + 54° (c 1.05, CHCl3); H NMR d 2.02, 2.03, 2.07, 2.18 (s, 12H, 4 ꢁ CH3), 3.43
(d, 1H, J1’a,1’b = 12.2 Hz, H-1’a), 3.49 (t, 1H, J3,4 = J4,5 = 10.0 Hz, H-4), 3.56 (d, 1H,
H-1’b), 3.67 (dd, 1H, J5’,6’a = 10.0 Hz, J6’a,6’b = 12.0 Hz, H-6’a), 3.79 (dd, 1H,
J5’,6’b = 3.0 Hz, H-6’b), 4.05–4.23 (m, 2H, H-5, 5’), 4.29 (dd, 1H, J5,6a = 2.1 Hz,
J6a,6b = 12.0 Hz, H-6a), 4.40 (dd, 1H, J5,6b = 3.8 Hz, H-6b), 4.51 (t, 1H,

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J3’,4’ = J4’,5’ = 6.0 Hz, H-4’), 4.75 (dd, 1H, J1,2 = 3.5 Hz, J2,3 = 10.0 Hz, H-2), 5.15
(t, 1H, H-3), 5.20 (d, 1H, H-3’), 5.51 (d, 1H, H-1). 13C NMR d 171.7, 171.5, 170.7,
169.6 (4 ꢁ COCH3), 105.8 (C-2’), 90.8 (C-1), 81.8 (C-5’), 73.7 (C-3’), 72.2 (C-3),
71.7 (C-5), 70.3 (C-2), 68.7 (C-4), 66.4 (C-6’), 64.6 (C-1’), 62.5 (C-6), 20.9, 20.8,
20.7 (4 ꢁ COCH3) and 19.7 (C-4’). HRMS-ESI (positive mode): calcd for
[M + Na] + 643.0500. Found 643.0493.
3-O-Acetyl-4-bromo-1,6-dichloro-1,4,6-trideoxy- -D-tagatofuranosyl 2,3,6-tri-
O-acetyl-4-chloro-4-deoxy- -D-galactopyranoside (47). Compound 45 (0.16 g,
0.28 mmol) was triflated and reacted with LiCl (0.21 g) in acetone (15 mL), as
described above, to give, after flash chromatography (ethyl acetate-hexane, 1:2), 47
1
(0.11 g, 63%) as a colourless syrup; [a]D + 82° (c 1.41, CHCl3); H NMR d 2.02,
2.06, 2.16 (s, 12H, 4 ꢁ CH3), 3.50–3.73 (m, 4H, H-1’a,b and H-6’a,b), 4.08–4.22 (m,
2H, H-6a,b), 4.29–4.35 (m, 1H, H-5’), 4.54 (dd, 1H, J3,4 = 3.5 Hz, J4,5 = 1.0 Hz, H-
4), 4.60–4.64 (m, 1H, H-5), 4.81 (dd, 1H, J3’,4’ = 5.9 Hz, J4’,5’ 4.5 Hz, H-4’), 5.21 (dd,
1H, J1,2 = 3.5 Hz, J2,3 = 10.8 Hz, H-2), 5.28 (dd, 1H, H-3), 5.41 (d, 1H, H-3’) and
5.53 (d, 1H, H-1). 13C NMR d 170.2, 170.2, 169.9, 169.6 (4 ꢁ COCH3), 104.5 (C-2’),
91.3 (C-1), 80.3 (C-5’), 72.5 (C-3’), 68.1 (C-3), 67.8 (C-5), 67.4 (C-2), 62.9 (C-6), 59.2
(C-4), 50.0 (C-4’), 45.0 (C-1’), 44.2 (C-6’) and 20.8, 20.6 (4 ꢁ COCH3). HRMS-ESI
(positive mode): calcd for [M + Na] + 648.9622:650.9592:652.9563:654.9543. Found:
648.9611:650.9595:652.9559:654.9548.
3-O-Acetyl-1,6-dichloro-1,4,6-trideoxy-4-iodo- -D-tagatofuranosyl 2,3,6-tri-O-
acetyl-4-chloro-4-deoxy- -D-galactopyranoside (48). Compound 46 (0.26 g, 0.419
mmol) was treated with trifluoromethanesulfonic anhydride (0.40 mL, 2.44 mmol) and
LiCl (0.25 g) in acetone (15 mL), to give, after column chromatography (ethyl acetate-
hexane, 1:2), 48 (0.19 g, 67%); [a]D + 77° (c 0.82, CHCl3); 1H NMR d 2.02, 2.02, 2.06,
2.15 (s, 12H, 4 ꢁ CH3), 3.54–3.76 (m, 4H, H-6’a,b and H-1’a,b), 3.87–3.93 (m, 1H, H-
5’), 4.10 (dd, 1H, J5,6a = 7.3 Hz, J6a,6b = 11.0 Hz, H-6a), 4.21 (dd, 1H, J5,6b = 6.0 Hz,
H-6b), 4.54 (dd, 1H, J3,4 = 3.5 Hz, J4,5 = 1.4 Hz, H-4), 4.62–4.67 (m, 1H, H-5), 4.80
(t, 1H, J3’,4’ = J4’,5’ = 6.0 Hz, H-4’), 5.10 (d, 1H, H-3’), 5.19 (dd, 1H, J1,2 = 3.5 Hz,
J2,3 = 10.8 Hz, H-2), 5.35 (dd, 1H, H-3) and 5.55 (d, 1H, H-1). 13C NMR d 170.2,
170.1, 169.9, 169.3 (4 ꢁ COCH3), 104.7 (C-2’), 91.5 (C-1), 80.1 (C-5’), 73.2 (C-3’),
68.1, 68.0, 67.4 (C-2, 3, 5), 62.6 (C-6), 59.1 (C-4), 48.5, 44.7 (C-1’, 6’), 27.6 (C-4’) and
20.8, 20.7 (4 ꢁ COCH3). HRMS-ESI (positive mode): calcd for [M + Na] +
696.9483:698.9453:700.9424:702.9394. Found: 696.9460:698.9424:700.9442:
702.9406.
4-Bromo-1,6-dichloro-1,4,6-trideoxy- -D-tagatofuranosyl 4-chloro-4-deoxy- -D-
galactopyranoside (49). Deacetylation (MeOH-NaOMe, pH ~10) of 47 (0.091 g,
0.145 mmol), as described for 29 afforded 49 as a colourless syrup (0.0612 g, 92%);
1
[a]D + 40° (c 2.87, MeOH); H NMR (D2O) d 4.26–4.29 (m, 2H, H-6a,b), 4.38–4.46
(m, 4H, H-1’a,b and H-6’a,b), 4.49 (dd, 1H, J1,2 = 4.0 Hz, J2,3 = 10.0 Hz, H-2), 4.47
(dd, 1H, J3,4 = 3.5 Hz, H-3), 4.96–5.02 (m, 1H, H-5’), 5.07–5.13 (m, 2H, H-4, 5),
5.34 (d, 1H, J3’,4’ = 5.2 Hz, H-3’), 5.45 (dd, 1H, J4’,5’ = 3.8 Hz, H-4’) and 6.00 (d, 1H,
H-1). 13C NMR (D2O) d 104.8 (C-2’), 94.6 (C-1), 79.8 (C-5’), 73.9 (C-3’), 71.1, 68.7,
68.6 (C-2, 3, 5), 63.6 (C-4), 60.6 (C-6), 55.8 (C-4’), 45.9, 43.9 (C-1’, 6’). HRMS-ESI

4,1’,4’,6’-Tetrahalodeoxysucrose Analogues
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(positive mode): calcd for [M + Na] + 480.9200:482.9179:484.9150:486.9120. Found:
480.9204:482.9183:484.9148:486.9128.
1,6-Dichloro-1,4,6-trideoxy-4-iodo- -D-tagatofuranosyl 4-chloro-4-deoxy- -D-
galactopyranoside (50). Deacetylation of 48 (0.18 g, 0.266 mmol) as described for
1
29 gave 50 as a yellowish syrup (0.12 g, 89%); [a]D + 51° (c 4.26, MeOH); H NMR
(D2O) d 4.26–4.48 (m, 7H, H-1’a,b, 6’a,b, H-6a,b and H-5’), 4.50 (dd, 1H, J1,2 = 4.0
Hz, J2,3 = 10.0 Hz, H-2), 4.85 (dd, 1H, J3,4 = 3.5 Hz, H-3), 4.88 (d, 1H, J3’,4’ = 5.9
Hz, H-3’), 5.13–5.18 (m, 2H, H-4, 5), 5.48 (dd, 1H, J4’,5’ = 4.0 Hz, H-4’) and 6.01 (d,
1H, H-1). 13C NMR (D2O) d 104.9 (C-2’), 94.9 (C-1), 78.9 (C-5’), 74.2 (C-3’), 71.4 (C-
5), 68.8, 68.7 (C-2, 3), 63.7 (C-4), 60.6 (C-6), 50.2, 44.1 (C-1’, 6’) and 36.6 (C-4’).
HRMS-ESI (positive mode): calcd for [M + Na] + 528.9060:530.9031:532.9001.
Found: 528.9057:530.9045:532.9012.
ACKNOWLEDGMENT
We thank the National University of Singapore for financial support for
this research.
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Received July 12, 2002
Accepted February 1, 2003