Synthesis of (6-2H)- and 6-deoxy-6-fluoro-L-galactose derivatives

Article abstract of DOI:10.1081/CAR-100102541

The selective oxidation of trimethylsilylated D-galactose diethyl dithioacetal using Collins reagent provided the corresponding D-galacto-hexodialdo dithioacetal. Successive acid hydrolysis, isopropylidenation, and cleavage of the dithioacetal group gave the 1,2;3,4-di-O-isopropylidene-L-galacto-hexodialdo-1,5-pyranose as a key intermediate for the synthesis of 6-fluoro- and 6-deutero-substituted L-fucose derivatives.

Full text of DOI:10.1081/CAR-100102541

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SYNTHESIS OF (6-2H)- AND 6-DEOXY-6-FLUORO-L-
GALACTOSE DERIVATIVES1
Meinolf Brackhagen a , Hanna Boye a & Christian Vogel b
a Department of Chemistry, Division of Organic Chemistry , University of Rostock ,
Buchbinderstra βe 9, Rostock, 18055, Germany
b Department of Chemistry, Division of Organic Chemistry , University of Rostock ,
Buchbinderstra βe 9, Rostock, 18055, Germany
Published online: 11 Dec 2006.
To cite this article: Meinolf Brackhagen , Hanna Boye & Christian Vogel (2001) SYNTHESIS OF (6-2H)- AND 6-DEOXY-6-
FLUORO-L-GALACTOSE DERIVATIVES1 , Journal of Carbohydrate Chemistry, 20:1, 31-43, DOI: 10.1081/CAR-100102541
To link to this article: http://dx.doi.org/10.1081/CAR-100102541
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J. CARBOHYDRATE CHEMISTRY, 20(1), 31–43 (2001)
SYNTHESIS OF (6-2H)- AND 6-DEOXY-6-FLUORO-
L-GALACTOSE DERIVATIVES1
Meinolf Brackhagen, Hanna Boye, and Christian Vogel*
University of Rostock, Department of Chemistry, Division of Organic
Chemistry, Buchbinderstraꢀe 9, 18055 Rostock, Germany
ABSTRACT
The selective oxidation of trimethylsilylated D-galactose diethyl
dithioacetal using Collins reagent provided the corresponding D-galacto-hexo-
dialdo dithioacetal. Successive acid hydrolysis, isopropylidenation, and cleav-
age of the dithioacetal group gave the 1,2;3,4-di-O-isopropylidene-L-galacto-
hexodialdo-1,5-pyranose as a key intermediate for the synthesis of 6-fluoro-
and 6-deutero-substituted L-fucose derivatives.
INTRODUCTION
Our laboratory studies the synthesis of oligosaccharides, present in human
milk, containing fucose residues with various markers. These labeled oligosaccha-
rides may then be used as potential tools to clarify the role that high concentrations
of complex carbohydrates in human milk play in infant nutrition.2 As part of our
ongoing interest in the preparation of L-fucose starting from D-galactose precur-
sors, we previously developed a synthetic approach for L-fucose. This included the
following synthetic steps: D-Galactose was converted into the D-galactose diethyl
dithioacetal, which was then reduced with high active Raney nickel to give L-fuci-
tol which was subsequently transformed into its 1,2,3,4,5-penta-O-trimethylsilyl
derivative. The trimethylsilyl ether of the primary alcohol could be selectively ox-
idized in the presence of secondary alcohols by Collins reagent providing, after
* Corresponding author. E-mail: christian.vogel@chemie.uni-rostock.de
1Dedicated to Professor Peter Köll on the Occasion of His 60th Birthday.
31
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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BRACKHAGEN, BOYE, AND VOGEL
acid hydrolysis, L-fucose in an overall yield of 87%.3 Based on this strategy, we
now report a route for the synthesis of L-galactose and L-fucose derivatives, re-
spectively, substituted at the C-6 position by a fluorine or deuterium atom.
RESULTS AND DISCUSSION
For the preparation of the dialdo sugar 6, suitable as a universal intermediate
for further modification at C-6 position, it is possible to proceed from D-galactose
diethyl dithioacetal 1 again (Scheme 1). In contrast to our previously reported ap-
proach to L-fucose,3 the dithioacetal 1 was quantitatively converted into the
2,3,4,5,6-penta-O-trimethylsilyl derivative 2 which was then immediately oxi-
dized by Collins reagent. Successive acid hydrolysis and isopropylidenation of the
crude dialdo sugar 3, which was formed as a result of the selective oxidation of a
trimethylsilyl ether of a primary alcohol in the presence of secondary alcohols, pro-
vided the fully protected derivative 5 in an overall yield of 40%. Cleavage of the
dithioacetal function was achieved by mercury salts in 86% yield. The analytical
data for 5 and 6 fully agree with the proposed structures. In the 1H NMR spectra
the three-bond coupling constants within the pyranose ring amount to 5.0 ꢁ 0.2
(J1,2), 2.2 ꢁ 0.1 (J2,3), 7.9 (J3,4), 1.8 ꢁ 0.2 (J4,5) and indicated the anticipated twist
conformation (2SO) of the six-membered ring.4
According to a procedure reported by M. Sharma and coworkers5 for 6-de-
oxy-6,6-difluoro-D-galactose, the key intermediate 6 was transformed into the 6,6-
gem-difluoro derivative 7 by treatment with diethylaminosulfur trifluoride (DAST)
24
in 63% yield (Scheme 1). The optical rotation of L-sugar 7, [ꢂ]D ꢃ41.5 (c 1.0,
Scheme 1.

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33
chloroform), and the corresponding D-sugar, [ꢂ]D22 -42.3 (c 1.0, chloroform), pre-
pared by Sharma et al.5 confirm the enantiomeric relation between both sugars,
whereas the minus sign of [ꢂ]D25 -40.1 (c 1.02, chloroform) for the L-sugar in a pa-
per of Sartorelli and co-workers6 must be a printer’s error.
Next, an alternative route for the synthesis of carbon backbone elongated L-
fucose derivatives2 was investigated, starting from 6 (Scheme 2). The Wittig reac-
tion with the alkylidene triphenylphosphorane of chain length C4 gave the alkene
8 in 68% yield. Successive hydrogenation (10, 94%), deisopropylidenation and
acetylation resulted in the target compound 12 in an overall yield of 19%, over
eight synthetic steps from 1.
The previously reported route involved the same number of synthetic steps
and furnished 12 in overall yield of 31%. Thus, the former procedure seems to be
superior compared with the latter one for the preparation of carbon backbone elon-
gated L-fucose derivatives. In our new synthesis the crucial oxidation of 2 limited
the overall yield. Nevertheless, the spacermodified L-fucose analogue 13 was pre-
pared proceeding from 6 by introduction of an additional functional group at the
end of the alkyl chain. Therefore, 4-carboxybutyl triphenylphosphonium bromide
was used in the Wittig reaction and gave compound 13 in 20% yield related to 1,
after the same sequence of synthetic steps as for the preparation of 12. The next
publication in this series will describe the synthesis of 13 by the former procedure
and its conversion into a GDP-L-fucose analogue.
Much more attractive is the introduction of fluorine or deuterium at the C-
6 position of L-galactose and L-fucose, respectively, starting from key interme-
diate 6. The reduction of the dialdo sugar 6 with lithium aluminium hydride or
lithium aluminium deuteride gave the L-galactose derivatives 14 and 15 in 84%
and 85%, respectively (Scheme 3). The introduction of a trifluoromethanesul-
fonyl group in 14 and 15 provided the C-6 activated derivatives 16 and 17 in
Scheme 2.

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BRACKHAGEN, BOYE, AND VOGEL
Scheme 3.
nearly quantitative yields. The reduction of 17 with sodium borohydride7 gave
the (6-H2)-L-fucose derivative 18 in 85% yield, whereas the substitution of the
triflyl group with fluorine resulted in the 6-deoxy-6-fluoro-L-galactose deriva-
tive 19 in an excellent 87% yield. By contrast, employing the p-toluenesulfonyl
function as a leaving group furnished 19 in only 35% yield.6 Both compounds 18
and 19 were deisopropylidenated and acetylated to provide the corresponding
deuterium and fluorine substituted L-fucose derivatives 20 and 21, respectively.
The structures of the compounds 14 - 21 are in accordance with all analytical data
and, as expected, the NMR data of these L-sugars are comparable with those of
the D-sugars described in the literature.8 In one of our next papers, we will de-
scribe the conversion of 20 and 21 into glycosyl donors and their coupling with
D-lactose acceptors to provide both deuterium and fluorine substituted oligosac-
charides of human milk.
EXPERIMENTAL
General Methods. Melting points were determined with a Boetius micro ap-
paratus BHMK 05 (Rapido, Dresden) and are uncorrected. Optical rotations were
measured for solutions in a 2-cm cell with an automatic polarimeter “GYROMAT”
(Dr. Kernchen Co.). NMR spectra were recorded with Bruker AC-250 or ARX-300
spectrometers, at 250 MHz or 300 MHz for 1H, and 62.9 MHz or 75.5 MHz for 13C,
respectively. Chemical shifts are given relative to the signal of internal tetram-
ethylsilane (ꢄ ꢅ 0). First order chemical shifts and coupling constants were ob-
tained from one-dimensional spectra, and assignment of proton resonances was
based on COSY experiments. Thin-layer chromatography (TLC) on precoated
plates of silica gel (Merck, Silica Gel 60, F254, 0.25 mm) was performed with the
following solvent systems (v/v): (A) heptane, (B) 10:1, (C) 9:1, (D) 8:1, (E) 5:1,
(F) 4:1, (G) 3:1, (H) 2:1, (I) 4:3 heptane-ethyl acetate, and (J) 4:1 ethyl acetate-

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35
methanol. The spots were made visible by spraying with methanolic 10% H2SO4
solution and charring them for 3-5 min with a heat gun. Detection of benzyl deriva-
tives was effected by UV fluorescence. Preparative flash chromatography and
HPLC was performed by elution from columns of slurry-packed Silica Gel 60
(Merck, 40-63 ꢆm) and Nucleosil 100-7 (Knauer, 7.0 ꢆm), respectively, with the
above solvent systems. All solvents and reagents were purified and dried accord-
ing to standard procedures.9 After classical work up of the reaction mixtures, the
organic layers as a rule, were dried over MgSO4, and then concentrated under re-
duced pressure (rotary evaporator).
2,3,4,5,6-Penta-O-trimethylsilyl-D-galactose Diethyl Dithioacetal (2). To a
solution of D-galactose diethyl dithioacetal (1, 2.86 g, 10 mmol) and hexamethyl-
disilazane (20.7 mL, 100 mmol) in dry pyridine (10 mL) was added
chlorotrimethylsilane (6.3 mL, 50 mmol) under argon at room temperature. After
stirring for 12 h (TLC solvent A Rf 0.21), the reaction mixture was diluted with di-
ethyl ether (50 mL) and filtered. The filtrate was concentrated, the residue was dis-
solved in diethyl ether (50 mL) and the solution again filtered. After removing the
solvent, the residue was codistilled with toluene (3 x 50 mL), and dried in high vac-
uum to yield 2 ( 6.1 g, 94%) as a colorless syrup: [ꢂ]D23 ꢃ5.4° (c 1.0, chloroform);
1H NMR (CDCl3) ꢄ 0.10 [s, 9H, Si(CH3)3], 0.14, [s, 18H, 2 x Si(CH3)3] , 0.15, 0.18
[2s, 18H, 2 x Si(CH3)3], 1.23, 1.24 (2t, 6H, J ꢅ 7.4 Hz, 2 x SCH2CH3), 2.64 (qd,
2H, J ꢅ 7.4 Hz, J ꢅ1.4 Hz, SCH2CH3), 2.74 (q, 2H, J ꢅ 7.4 Hz, SCH2CH3), 3.62
(dd, 1H, J5,6 ꢅ 6.2 Hz, J6,6′ ꢅ 10.3 Hz, H-6), 3.71 (d, 1H, J1,2 ꢅ 4.2 Hz, H-1), 3.76-
3.81 (m, 2H, H-5, H-6’), 3.98 (dd, 1H, J2,3 ꢅ 2.5 Hz, H-2), 4.13-4.19 (m, 2H, H-
3, H-4); 13C NMR (CDCl3) ꢄ -0.49, 0.75, 1.27, 1.30, 1.61 (5 x SiCH3), 14.41, 14.47
(2 x SCH2CH3), 24.37, 25.57 (2 x SCH2CH3), 55.30 (C-1), 64.05 (C-6), 74.04,
75.63, 76.05, 76.45 (C-2, C-3, C-4, C-5).
Anal. Calcd for C25H62O5S2Si5 (647.30): C, 46.39; H, 9.65; S, 9.91. Found:
C, 46.27, H, 9.48, S, 10.03.
2,3,4,5-Tetra-O-trimethylsilyl-D-galacto-hexodialdose-1 Diethyl Dithioac-
etal (3). To dry pyridine (150 mL) was added chromium(VI)oxide (17.0 g, 170
mmol) in portions under argon with cooling (ice bath). After stirring for one hour
at room temperature, a solution of compound 2 (22.0 g, 34.0 mmol) in dry pyridine
(50 mL) was added dropwise to the Collins reagent. When the reaction was com-
plete (2.5 h; TLC solvent B Rf 0.47), toluene (250 mL) was added, and the result-
ing solids were removed by filtration through silica gel. The filtrate was concen-
trated, the residue codistilled with toluene (150 mL), and dried in vacuo. The crude
product 3 (13 g, brown syrup) was used in the next step without further purifica-
tion. 1H NMR (CDCl3) ꢄ 0.12 [s, 9H, Si (CH3)3], 0.14 [s, 18H, 2 x Si(CH3)3], 0.17
[s, 9H, Si(CH3)3], 1.20-1.28 (m, 6H, 2 x SCH2CH3), 2.65 (q, 2H, J ꢅ 7.2 Hz,
SCH2CH3), 2.76 (q, 2H, J ꢅ 7.5 Hz, SCH2CH3), 3.88 (d, 1H, H-5), 3.94 (d, 1H,
J
1,2 ꢅ 4.6 Hz, H-1), 4.05 (dd, 1H, J2,3 ꢅ 2.2 Hz, H-2), 4.17 (dd, 1H, J4,5 ꢅ 2.9 Hz,
H-4), 4.32 (dd, 1H, J3,4 ꢅ 8.0 Hz, H-3), 9.71 (s, 1H, H-6); 13C NMR (CDCl3) ꢄ
0.25, 0.62, 0.94, 1.00 (4 x SiCH3), 14.34, 14.41 (2 x SCH2CH3), 24.35, 25.95 (2 x
SCH2CH3), 55.23 (C-1), 74.96, 75.47, 77.68, 79.39 (C-2, C-3, C-4, C-5), 199.44
(C-6).

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BRACKHAGEN, BOYE, AND VOGEL
1,2;3,4-Di-O-isopropylidene-L-galacto-hexodialdo-1,5-pyranose-6 Diethyl
Dithioacetal (5). A solution of crude 3 (26 g) in tetrahydrofuran (330 mL), acetic
acid (150 mL) and water (90 mL) was stirred for 24 h at room temperature (TLC
solvent J Rf 0.59). The solution was then concentrated, the residue codistilled with
toluene (3 x 300 mL), and dried in high vacuum. The crude D-galacto-hexodial-
dose-1-diethyl dithioacetal (4, 15 g, light brown syrup) was isopropylidenated
without further characterization. Thus, to a solution of crude 4 (15 g) in dry ace-
tone (200 mL) were added 2,2-dimethoxypropane (50 mL) and concd sulfuric acid
(0.5 mL). The reaction mixture was stirred for two hours at room temperature un-
der argon. When the reaction was complete (TLC solvent F Rf 0.42), sodium car-
bonate (3.0 g) was added, and the suspension was stirred for additional 15 min. The
solids were then filtered off, and the filtrate was concentrated. The residue was pu-
rified by MPLC (eluent solvent B) to provide 5 (9.9 g, 40% related to 2) as a col-
orless syrup: [ꢂ]D23 ꢃ36.4° (c 1, chloroform); 1H NMR (CDCl3) ꢄ 1.25, 1.26 (2t,
6H, J ꢅ 7.5 Hz, 2 x SCH2CH3), 1.31, 1.34, 1.43, 1.51 [4s, 12H, 2 x C(CH3)2], 2.61-
2.79 (m, 4H, 2 x SCH2CH3), 3.72 (dd, 1H, J5,6 ꢅ 10.6 Hz, H-5), 4.11 (d, 1H, H-6),
4.30 (dd, 1H, J2,3 ꢅ 2.2 Hz, H-2), 4.61 (dd, 1H, J3,4 ꢅ 7.9 Hz, H-3), 4.66 (dd, 1H,
J
4,5 ꢅ 1.6 Hz, H-4), 5.59 (d, 1H, J1,2 ꢅ 5.2 Hz, H-1); 13C NMR (CDCl3) ꢄ 13.94,
14.50 (2 x SCH2CH3), 24.26 (2 x SCH2CH3, two signals are isochronic), 24.51,
24.83 [C(CH3)2], 25.91 [C(CH3)2, two signals are isochronic], 69.73 (C-5), 70.57,
71.21, 71.33 (C-2, C-3, C-4), 97.03 (C-1), 108.70, 109.30 [2 x C(CH3)2].
Anal. Calcd for C16H28O5S2 (364.52): C, 52.72; H, 7.74; S, 17.59. Found: C,
52.58, H, 7.61; S, 17.68.
1,2;3,4-Di-O-isopropylidene-ꢂ-L-galacto-hexodialdo-1,5-pyranose (6). To a
stirred solution of 5 (6.1 g, 16.7 mmol) in acetone (250 mL) were successively
added yellow mercury(II)oxide (8.7 g, 40.2 mmol), mercury(II)chloride (8.7 g,
32.0 mmol), and water (25 mL). The resulting suspension was stirred for two hours
at room temperature (TLC solvent F Rf 0.36). The suspension was then filtered
through a layer of Celite, and the filtrate was concentrated. The residue was dis-
solved in chloroform (200 mL), successively washed with aq 1 N KI (2 x 70 mL),
brine (2 x 70 mL), dried, and concentrated. The residue was codistilled with
toluene (3 x 100 mL) to give 6 (3.7 g, 86%) as a colorless syrup, which was used
immediately for the next reaction step without further purification. An analytically
pure sample was obtained by HPLC (eluent solvent E): [ꢂ]D25 ꢃ116.8 (c 1.0, chlo-
1
roform); IR (KBr) 1741 cm-1 (CꢅO); H NMR (CDCl3) ꢄ 1.30, 1.33, 1.42, 1.49
[4s, 12H, 2 x C(CH3)2], 4.17 (d, 1H, H-5), 4.36 (dd, 1H, J2,3 ꢅ 2.3 Hz, H-2), 4.57
(dd, 1H, J4,5 ꢅ 2.0 Hz, H-4), 4.64 (dd, 1H, J3,4 ꢅ 7.9 Hz, H-3), 5.65 (d, 1H, J1,2 ꢅ
4.8 Hz, H-1), 9.59 (s, 1H, H-6); 13C NMR (CDCl3) ꢄ 24.21, 24.76, 25.76, 25.96 [2
x C(CH3)2], 70.39, 70.50, 71.71 (C-2, C-3, C-4), 73.18 (C-5), 96.22 (C-1), 108.98,
110.00 [2 x C(CH3)2], 200.13 (C-6).
Anal. Calcd for C12H18O6 (258.27): C, 55.80; H, 7.02. Found: C, 55.63, H,
7.18.
6-Deoxy-6,6-difluoro-1,2;3,4-di-O-isopropylidene-ꢂ-L-galactopyranose (7).
To a solution of 6 (439 mg, 1.7 mmol) in dry dichloromethane (10 mL) was added

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(6-2H)- AND 6-DEOXY-6-FLUORO-L-GALACTOSE DERIVATIVES
37
dropwise diethylaminosulfur trifluoride (DAST, 0.6 mL, 4.54 mmol) under argon
at 5 °C. After stirring for 24 h at ambient temperature (TLC solvent G Rf 0.44), wa-
ter (2 mL) was added and, after a few minutes, the mixture was diluted with chlo-
roform (50 mL). The organic layer was washed with cold sat aq NaHCO3 (2 x 25
mL), water (2 x 25 mL), dried, and concentrated. The purification by HPLC (elu-
ent solvent F) provided 7 (300 mg, 63%) as a light brown syrup, which crystallized
24
after a few days in the refrigerator: mp 43-45 °C; [ꢂ]D ꢃ41.5° (c 1.0, chloro-
form); 1H NMR (CDCl3) ꢄ 1.33, 1.34, 1.44, 1.53 [4 s, 12 H, 2 x C(CH3)2], 3.87 (m,
1H, H-5), 4.34 (dd, 1H, J2,3 ꢅ 2.5 Hz, H-2), 4.36 (m, 1H, H-4), 4.64 (ddd, 1H, J3,4
ꢅ 7.9 Hz, 5J3,F ꢅ 1.5 Hz, H-3), 5.54 (dd, 1H, J1,2 ꢅ 4.9 Hz, 5J1,F ꢅ 1.9 Hz, H-1),
5.83 (ddd, 1H, J5,6 ꢅ 6.7 Hz, J6,F ꢅ 54.0 Hz, J6,F′ ꢅ 59.8 Hz, H-6); 13C NMR
(CDCl3) ꢄ 24.23, 24.83, 25.78, 25.97 [2 x C(CH3)2], 67.98 (dd, JC,F ꢅ 32.3 Hz,
J
C,F’ꢅ 24.0 Hz, C-5), 69.71 (d, JC,F ꢅ 7.4 Hz, C-4), 70.26 (C-2), 70.33 (C-3), 95.94
(C-1), 109.14, 109.95 [2 x C(CH3)2], 114.45 (dd, JC,F ꢅ 237.8 Hz, JC,F′ ꢅ 245.1
Hz, C-6); 19F NMR (CDCl3) ꢄ -55.8 (d, Jꢅ 279.4 Hz, F), -58.0 (d, Jꢅ 279.4, F’).
Anal. Calcd for C12H18O5F2 (280.27): C, 51.42; H, 6.47. Found: C, 51.56, H,
6.42.
1,2;3,4-Di-O-isopropylidene-6,7,8,9,10-pentadeoxy-ꢂ-L-galacto-dec-6-
enopyranose (8). To a suspension of butyl triphenylphosphonium bromide (2.4 g,
6.0 mmol) in dry tetrahydrofuran (15 mL) was added lithium hexamethyldisi-
lazanate (6.0 mL of a 1N soln in tetrahydrofuran). After stirring for one hour under
argon, a solution of 6 (1.0 g, 3.9 mmol) in dry tetrahydrofuran (6 mL) was drop-
wise added, and stirring was continued for 3 h (TLC solvent H Rf 0.63). Heptane
(50 mL) was then added, and the mixture was concentrated. The residue was dis-
solved in heptane (100 mL) and the precipitating salts were filtered off. The filtrate
was washed with water (2 x 50 mL), dried and concentrated. The residue was pu-
rified by MPLC (eluent ethyl acetate gradient 0%→11% in heptane) to yield 8 (780
23
1
mg, 68 %) as a colorless syrup: [ꢂ]D ꢃ107.8° (c 1.0, chloroform); H NMR
(CDCl3) ꢄ 0.89 (t, 3H, J ꢅ 7.3 Hz, H-10, H-10′, H-10′′), 1.32 [s, 6H, C(CH3)2],
1.39 (m, 2H, H-9, H-9’), 1.49, 1.55 [2 s, 6H, C(CH3)2], 2.06 (m, 2H, H-8, H-8’),
4.12 (dd, 1H, J4,5 ꢅ 1.7 Hz, H-4), 4.29 (dd, 1H, J2,3 ꢅ 2.2 Hz, H-2), 4.57 (dd, 1H,
J
5,6 ꢅ 7.1, H-5), 4.59 (dd, 1H, J3,4 ꢅ 7.8 Hz, H-3), 5.53 (d, 1H, J1,2 ꢅ 5.2 Hz, H-
1), 5.60 (m, 1H, H-7), 5.66 (m, 1H, H-6); 13C NMR (CDCl3) ꢄ 13.71 (C-10), 22.55
(C-9), 24.24, 24.85, 25.89, 26.02 [2 x C(CH3)2], 30.11 (C-8), 63.66 (C-5), 70.17
(C-2), 70.80 (C-3), 73.46 (C-4), 96.50 (C-1), 108.24, 109. 6 [2 x C(CH3)2], 125.15
(C-7), 134.23 (C-6).
Anal. Calcd for C16H26O5 (298.38): C, 46.40; H, 8.78. Found: C, 46.42; H,
8.69.
1,2;3,4-Di-O-isopropylidene-10-methoxycarbonyl-6,7,8,9,10-pentadeoxy-
ꢂ-L-galacto-dec-6-enopyranose (9). To a suspension of 4-carboxybutyl triph-
enylphosphonium bromide (2.65 g, 6.0 mmol) in dry tetrahydrofuran (15 mL) was
added lithium hexamethyldisilazanate (12.0 mL of a 1 N soln in tetrahydrofuran).
After stirring for one hour under argon, a solution of 6 (1.0 g, 3.9 mmol) in dry
tetrahydrofuran (6 mL) was dropwise added and stirring was continued for 3 h. As

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BRACKHAGEN, BOYE, AND VOGEL
soon as aldehyde 6 was consumed (TLC solvent H), water (100 mL) and heptane
(30 mL) were added, and the solution were filtered. The aqueous layer was washed
with heptane (2 x 25 mL) and concentrated to a volume of 20 mL. For esterifica-
tion of the free carboxy function, dichloromethane (30 mL), iodomethane (2.6 mL,
40 mmol) and tertrabutylammonium bromide (1.6 g, 5.0 mmol) were added, and
the mixture was stirred vigorously for 20 h (TLC solvent G Rf 0.28). The layers
were separated, and the aqueous layer was extracted with dichloromethane (2 x 15
ml). Finally, the combined organic layers were dried, and concentrated. The
residue was purified by MPLC (eluent ethyl acetate gradient 0%→20% in heptane)
23
to provide 9 (965 mg, 70%) as a colorless syrup: [ꢂ]D ꢃ89.1° (c 1.0, chloro-
form); 1H NMR (CDCl3) ꢄ 1.31, 1.44, 1.53 [3s, 12H, 2 x C(CH3)2], 1.71, 2.13 (2m,
4H, H-8, H-8′,H-9, H-9′), 2.29 (t, 2H, J ꢅ 7.3 Hz, H-10, H-10′), 3.63 (s, 3H,
CO2CH3), 4.11 (dd, 1H, J4,5 ꢅ 2.0 Hz, H-4), 4.28 (dd, 1H, J2,3 ꢅ 2.3 Hz, H-2), 4.52
(dd, 1H, J5,6 ꢅ 7.3, H-5), 4.58 (dd, 1H, J3,4 ꢅ 7.9 Hz, H-3), 5.52 (d, 1H, J1,2 ꢅ 5.0
Hz, H-1), 5.58 (m, 1H, H-7), 5.62 (m, 1H, H-6); 13C NMR (CDCl3) ꢄ 24.59 (C-9),
24.31, 24.90, 25.96, 26.15 [2 x C(CH3)2], 27.44 (C-8), 33.40 (C-10), 51.53
(CO2CH3), 63.66 (C-5), 70.20 (C-2), 70.84 (C-3), 73.39 (C-4), 96.53 (C-1),
108.36, 109.18 [2 x C(CH3)2], 126.16 (C-7), 133.21 (C-6), 173.82 (CO2CH3).
Anal. Calcd for C18H28O7 (356.41): C, 61.35; H, 6.86. Found: C, 61.21; H,
6.70.
Hydrogenation of the Alkenes 8 and 9. To a solution of alkene 8 or 9 (4.0
mmol) in heptane (10 mL) palladium-on-charcoal (120 mg) was added. The solu-
tion was stirred in an atmosphere of hydrogen for 20 h at ambient temperature.
When the reaction was complete (TLC controlled), the mixture was filtered over
Celite, the filtrate was concentrated, and the analytically pure residue dried in
vacuo.
1,2;3,4-Di-O-isopropylidene-6,7,8,9,10-pentadeoxy-ꢂ-L-galacto-decopyra-
23
nose (10). (1.13 g, 94%; TLC solvent H Rf 0.64), colorless syrup: [ꢂ]D ꢃ61.2°
1
(c 1.0, chloroform); H NMR (CDCl3) ꢄ 0.86 (t, 3H, J ꢅ 6.2 Hz, H-10, H-10’),
1.22-1.68 (m, 8H, H-6,H-6′,H-7,H-7′,H-8,H-8’,H-9, H-9’), 1.31, 1.33, 1.44, 1.50
[4s, 12H, 2 x C(CH3)2], 3.69 (m, 1H, H-5), 4.11 (dd, 1H, J4,5 ꢅ 1.7 Hz, H-4), 4.27
(dd, 1H, J2,3 ꢅ 2.3 Hz, H-2), 4.56 (dd, 1H, J3,4 ꢅ 8.0 Hz, H-3), 5.52 (d, 1H, J1,2 ꢅ
5.2 Hz, H-1); 13C NMR (CDCl3) ꢄ 14.09 (C-10), 22.56 (C-9), 25.36 (C-7), 24.33,
24.94, 26.00, 26.03 [2 x C(CH3)2], 30.08, 31.70 (C-6,C-9), 67.37 (C-5), 70.55 (C-
2), 70.90 (C-3), 72.86 (C-4), 96.61 (C-1), 108.22, 108.91 [2 x C(CH3)2].
Anal. Calcd for C16H28O5 (300.39): C, 63.97; H, 9.39. Found: C, 64.05; H,
9.31.
1,2;3,4-Di-O-isopropylidene-10-methoxycarbonyl-6,7,8,9,10-pentadeoxy-
ꢂ-L-galacto-undecopyranose (11). (1.33 g, 93%; TLC solvent G Rf 0.32), colorless
25
syrup: [ꢂ]D ꢃ46.6° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.26-1.69 (m, 8H,
H-6,H-6′,H-7,H-7′,H-8,H-8′,H-9, H-9′), 1.29, 1.30, 1.41, 1.48 [4s, 12H, C(CH3)2],
2.27 (t, 2H, J ꢅ 7.6, H-10, H-10’, H-10′′), 3.62 (s, 3H, CO2CH3), 3.67 (m, 1H, H-
5), 4.08 (dd, 1H, J4,5 ꢅ 1.8 Hz, H-4), 4.25 (dd, 1H, J2,3 ꢅ 2.3 Hz, H-2), 4.54 (dd,
1H, J3,4 ꢅ 7.9 Hz, H-3), 5.49 (d, 1H, J1,2 ꢅ 5.3 Hz, H-1); 13C NMR (CDCl3) ꢄ

ORDER
REPRINTS
(6-2H)- AND 6-DEOXY-6-FLUORO-L-GALACTOSE DERIVATIVES
39
24.32, 24.82, 25.98, 26.03 [2 x C(CH3)2], 24.92, 25.34 (C-7,C-8) 28.94, 29.92 (C-
6,C-9), 34.01 (C-10), 51.43 (CO2CH3), 67.26 (C-5), 70.51 (C-2), 70.88 (C-3),
72.81 (C-4), 96.57 (C-1), 108.22, 108.93 [2 x C(CH3)2], 174.20 (CO2CH3).
Anal. Calcd for C18H30O7 (358.42): C, 60.31; H, 8.43. Found: C, 60.22; H,
8.51.
Successive Deisopropylidenation and Acetylation of 10 and 11. A solution of
10 (901 mg, 3.0 mmol) or 11 (1.08 g, 3.0 mmol) in 90% trifluoroacetic acid (20
mL) was stirred for two hours at room temperature (TLC solvent J). The mixture
was then concentrated, the residue codistilled with toluene (3 x 30 mL), and dried
in high vacuum. The residue was dissolved in acetic anhydride (20 mL), and the
solution was cooled to 4 °C. After addition of 70% perchloric acid (0.2 mL), the
solution was stirred for 3.5 h at 4 °C under argon. When the reaction was complete
(TLC solvent H), the mixture was poured into ice-water (350 mL). After stirring
for one hour, the aqueous layer was extracted with chloroform (2 x 150 mL). The
combined organic layers were washed with cold sat aq NaHCO3 (2 x 150 mL), wa-
ter (2 x 150 mL), dried, and concentrated. The crude products were purified by
MPLC (eluent ethyl acetate gradient 0% → 25% in heptane).
1,2,3,4-Tetra-O-acetyl-6,7,8,9,10-pentadeoxy-ꢂ?ꢀ-L-galacto-decopyranose
(12). (851 mg, 73%), colorless syrup: For analytical data see lit.2
1,2,3,4-Tetra-O-acetyl-10-methoxycarbonyl-6,7,8,9,10-pentadeoxy-ꢂ-L-
galacto-decopyranose (13ꢂ). (700 mg, 52%; TLC solvent H Rf 0.42), colorless
syrup: [ꢂ]D27 -111.3° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.24, 1.33, 1.50, 1.40,
1.55, 1.59 (6m, 8H, H-6,H-6′,H-7, H-7′,H-8, H-8′,H-9, H-9′), 1.96, 1.98, 2.11, 2.13
(4s, 12H, 4 x OCOCH3), 2.24 (t, 2H, H-10, H-10’), 3.62 (s, 3H, CO2CH3), 3.99 (m,
1H, H-5); 5.26 (m, 1H, H-4), 5.27 (m, 1H, H-3), 5.34 (m, 1H, H-2), 6.30 (d, 1H, 0.1
Hz, H-1); 13C NMR (CDCl3) ꢄ 20.44, 20.54, 20.64, 20.78 (4 x OCOCH3), 24.54
(C-9), 24.74 (C-7), 28.75 (C-8) 29.78 (C-6), 33.78 (C-10), 51.33 (CO2CH3), 68.13
(C-4), 69.25 (C-3), 70.92 (C-2, C-5, two signals are isochronic), 89.90 (C-1),
168.96, 169.31, 170.03, 170.31 (4 x OCOCH3), 173.86 (CO2CH3).
Anal. Calcd for C20H30O11 (446.45): C, 53.81; H, 6.77. Found: C, 53.69; H,
6.56.
1,2,3,4-Tetra-O-acetyl-10-methoxycarbonyl-6,7,8,9,10-pentadeoxy-ꢀ-L-
galacto-decopyranose (13ꢀ). (350 mg, 26%; TLC solvent H Rf 0.40), colorless
crystals: mp 75 °C (from ethyl acetate-heptane); [ꢂ]D22 -24.0° (c 1.5, chloroform);
1H NMR (CDCl3) ꢄ 1.28, 1.37, 1.30, 1.40, 1.55, 1.60 (6m, 8H, H-6,H-6′,H-7, H-
7’,H-8, H-8′,H-9, H-9′), 1.94, 1.99, 2.07, 2.13 (4s, 12H, 4 x OCOCH3), 2.24 (t, 2H,
H-10, H-10′), 3.61 (s, 3H, CO2CH3), 3.68 (m, 1H, H-5), 5.01 (m, 1H, J3,4 ꢅ 3.6 Hz,
H-3), 5.26 (m, 1H, H-4), 5.27 (dd, 1H, J2,3 ꢅ10.4 Hz, H-2), 5.60 (d, 1H, J1,2 ꢅ 8.2
Hz, H-1); 13C NMR (CDCl3) ꢄ 20.45, 20.54, 20.64, 20.73 (4 x OCOCH3), 24.56
(C-9), 24.83 (C-7), 28.64 (C-8), 29.84 (C-6), 33.81 (C-10), 51.34 (CO2CH3),
68.16(C-2), 69.04 (C-4), 71.33 (C-3), 74.16 (C-5), 92.34 (C-1), 168.99, 169.32,
169.87, 170.31 (4 x OCOCH3), 173.89 (CO2CH3).
Anal. Calcd for C20H30O11 (446.45): C, 53.81; H, 6.77. Found: C, 53.82; H,
6.49.

ORDER
REPRINTS
40
BRACKHAGEN, BOYE, AND VOGEL
Reduction of the Dialdo Sugar 6 to the Corresponding L-Galactose Deriva-
tives 14 and 15. To a suspension of lithium aluminium hydride (1.20 g, 31.6 mmol)
or lithium aluminium deuteride (1.33 g, 31.6 mmol) in dry tetrahydrofuran (100
mL) was added a solution of 6 (6.3 g, 24.4 mmol) in dry tetrahydrofuran (50 mL).
The mixture was then stirred for 3.5 h at room temperature under argon (TLC sol-
vent I Rf 0.30). The workup involved first destroying the hydride excess by addi-
tion of sat aq ammonium chloride (approximately 20 mL). After filtration, the so-
lution was concentrated to a volume of about 20 mL, and chloroform (300 mL) was
added. The organic layer was then extracted with brine (2 x 100 mL), dried, and
concentrated.The crude products were purified by MPLC (eluent ethyl acetate gra-
dient 0%→45% in heptane).
1,2;3,4-Di-O-isopropylidene-ꢂ-L-galactopyranose (14). (5.32 g, 84%), color-
less syrup: [ꢂ]D23 ꢃ54.3° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.32, 1.33, 1.44,
1.52 [4s, 12H, 2 x C(CH3)2], 2.21 (brs, OH), 3.73 (dd, 1H, J5,6 ꢅ 7.3 Hz, J6,6’ ꢅ
14.9 Hz, H-6), 3.79-3.91 (m, 2H, H-5,H-6’), 4.26 (dd, 1H, J4,5 ꢅ 1.5 Hz, H-4), 4.26
(dd, 1H, J2,3 ꢅ 2.4 Hz, H-2), 4.60 (dd, 1H, J3,4 ꢅ 7.9 Hz, H-3), 5.55 (d, 1H, J1,2 ꢅ
4.9 Hz, H-1); 13C NMR (CDCl3) ꢄ 24.23, 24.89, 25.87, 25.98 [2 x C(CH3)2], 62.30
(C-6), 68.01 (C-5), 70.48, 70.68 (C-2,C-3), 71.55 (C-4), 96.24 (C-1), 108.64,
109.42 [2 x C(CH3)2].
Anal. Calcd for C12H20O6 (260.29): C, 55.37; H, 7.74. Found: C, 55.46; H,
7.63.
(6R,S)- 1,2;3,4-Di-O-isopropylidene-ꢂ-L-(6-2H)-galactopyranose (15). (5.42
g, 85 %), colorless syrup: [ꢂ]D23 ꢃ53.4° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ
1.29, 1.30, 1.41, 1.49 [4s, 12H, 2 x C(CH3)2], 2.34 (brs, OH), 3.65-3.85 (m, 2H, H-
5,H-6R,H-6S), 4.23 (dd, 1H, J4,5 ꢅ 1.8 Hz, H-4), 4.29 (dd, 1H, J2,3 ꢅ 2.5 Hz, H-
2), 4.57 (dd, 1H, J3,4 ꢅ 7.9 Hz, H-3), 5.52 (d, 1H, J1,2 ꢅ 5.1 Hz, H-1); 13C NMR
(CDCl3) ꢄ 24.31, 24.91, 25.91, 26.00 [2 x C(CH3)2], 61.85 (t, JC,D ꢅ 21.9 Hz, C-
6), 68.12 (C-5), 70.58, 70.75 (C-2,C-3), 71.50 (C-4), 96.27 (C-1), 108.64, 109.42
ꢃ
[2 x C(CH3)2]; CI mass spectrum (isobutane): m/z 261 (C12H19O6D , 3%), 246
(C11H16O6Dꢃ, 100%], 204 (96%).
Anal. Calcd for C12H19O6D (261.28): C, 55.16. Found: C, 55.04.
Introduction of the Trifluoromethanesulfonyl Group in 14 and 15. To a solu-
tion of 14 (7.50 g, 28.8 mmol) or 15 (7.52g, 28.8 mmol) and collidine (7.5 mL, 56.6
mmol) in dry dichloromethane (300 mL) was added a solution of trifluo-
romethanesulfonic acid anhydride (7.5 mL, 45.8 mmol) in dry dichloromethane
(30 mL). The reaction mixture was stirred for two hours at room temperature un-
der argon (TLC controlled). The mixture was then poured into ice-water (300 mL),
the organic layer separated, and the aqueous layer extracted with chloroform (2 x
100 ml). The combined organic layers were washed with cold aq 15% NaHSO4 (2
x 250 mL), ice-water (2 x 250 mL), cold sat aq NaHCO3 (2 x 250 mL), water (2 x
250 mL), dried, and concentrated. After drying in high vacuum, the crude com-
pounds 16 and 17 were used in the next step without further purification.
1,2;3,4-Di-O-isopropylidene-6-O-trifluoromethanesulfonyl-ꢂ-L-galactopy-
ranose (16). (10.7 g, 95%; TLC solvent F Rf 0.38), colorless crystals: mp 47 °C;
[ꢂ]D24 ꢃ47.4° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.29, 1.30, 1.44, 1.53 [4s,

ORDER
REPRINTS
(6-2H)- AND 6-DEOXY-6-FLUORO-L-GALACTOSE DERIVATIVES
41
12H, 2 x C(CH3)2], 4.10 (ddd, 1H, J5,6 ꢅ 4.9 Hz, J5,6’ ꢅ 6.7 Hz, H-5), 4.23 (d, 1H,
4,5 ꢅ 2.1 Hz, H-4), 4.35 (dd, 1H, J2,3 ꢅ 2.7 Hz, H-2), 4.57 (dd, 1H, J6,6’ ꢅ 10.5
J
Hz, H-6), 4.63 (dd, 1H, H-6’), 4.64 (dd, 1H, J3,4 ꢅ 8.0 Hz, H-3), 5.55 (d, 1H, J1,2
ꢅ 4.9 Hz, H-1); 13C NMR (CDCl3) ꢄ 24.38, 24.86, 25.85, 26.94 [2 x C(CH3)2],
66.06 (C-5), 70.20, 70.37, 70.63 (C-2,C-3,C-4), 74.67 (C-6), 96.12 (C-1), 109.14,
110.14 [2 x C(CH3)2], 118.53 (q, JC,F ꢅ 314.5 Hz, CF3).
(6R,S)-1,2;3,4-Di-O-isopropylidene-6-O-trifluoromethanesulfonyl-ꢂ-L-(6-
2H)-galactopyranose (17). (10.65 g, 94%; TLC solvent F Rf 0.39, analytical sam-
ple by HPLC eluent solvent D), light brown syrup: [ꢂ]D23 ꢃ44.6° (c 1.0, chloro-
1
form); H NMR (CDCl3) ꢄ?1.31, 1.42, 1.51 [3s, 12H, C(CH3)2], 4.09 (m, 1H,
H-5), 4.23 (d, 1H, J4,5 ꢅ 2.1 Hz, H-4), 4.34 (dd, 1H, J2,3 ꢅ 2.7 Hz, H-2), 4.55, 4.60
(2d, 1H, J ꢅ 7.7 Hz, J ꢅ 4.4 Hz, (R,S)H-6), 4.63 (dd, 1H, J3,4 ꢅ 7.6 Hz, H-3), 5.52
(d, 1H, J1,2 ꢅ 4.8 Hz, H-1); 13C NMR (CDCl3) ꢄ 24.35, 24.82, 25.82, 26.90 [2 x
C(CH3)2], 65.99 (C-5), 70.20, 70.37, 70.63 (C-2,C-3,C-4), 74.39 (t, JC,D ꢅ 24.0
Hz, C-6), 96.10 (C-1), 109.11, 110.11 [2 x C(CH3)2], 118.63 (q, JC,F ꢅ 319.6 Hz,
CF3).
6-Deoxy-1,2;3,4-di-O-isopropylidene-ꢂ-L-(6-2H)-galactopyranose (18). To
a solution of 17 (6.9 g, 17.5 mmol) in dry acetonitrile (250 mL) was added sodium
borohydride (2.06 g, 54.4 mmol), and the mixture was stirred for 48 h at room tem-
perature under argon. When the reaction was complete (TLC solvent D Rf 0.53),
the mixture was filtered through a layer of silica gel and poured into ice-water (250
ml). The aqueous layer was extracted with chloroform (2 x 150 mL), and the com-
bined organic layers were washed with water, dried, and concentrated. Purification
24
by MPLC (eluent solvent D) provided 18 (3.66 g, 85%) as colorless syrup: [ꢂ]D
ꢃ52.7° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.23 (d, 2H, J5,6 ꢅ 7.7 Hz, H-6,
H-6′), 1.30, 1.33, 1.43, 1.49 [4s, 12H, 2 x C(CH3)2], 3.88 (m, 1H, H-5), 4.05 (dd,
1H, J4,5ꢅ 1.7 Hz, H-4), 4.26 (dd, 1H, J2,3 ꢅ 2.0 Hz, H-2), 4.56 (dd, 1H, J3,4 ꢅ 7.9
Hz, H-3), 5.49 (d, 1H, J1,2 ꢅ 5.3 Hz, H-1); 13C NMR (CDCl3) ꢄ 15.54 (t, JC,D ꢅ
19.6 Hz, C-6), 24.41, 24.87 [C(CH3)2], 25.99 [C(CH3)2 two signals are isochronic],
63.40 (C-5), 70.34, 70.94 (C-3,C-4), 73.51 (C-2), 96.52 (C-1), 108.16, 108.89 [2 x
C(CH3)2]; CI mass spectrum (isobutane): m/z 246 (C12H20O5Dꢃ, 100%), 230
(C11H16O5Dꢃ, 95%), 188 (90%).
Anal. Calcd for C12H19O5D (245.29): C, 58.76; H. Found: C, 58.73.
6-Deoxy-6-fluoro-1,2;3,4-di-O-isopropylidene-ꢂ-L-galactopyranose (19).
To a solution of 16 (10.7 g, 27.3 mmol) in dry dichloromethane (300 mL) was
dropwise added a 1 M solution of tetrabutylammonium fluoride in dry tetrahydro-
furan (100 mL). After stirring for 18 h at room temperature under argon (TLC sol-
vent D Rf 0.20), the reaction mixture was concentrated, and the residue dissolved
in chloroform (400 ml). The organic phase was extracted with water (3 x 100 ml),
dried and concentrated. Purification by MPLC (eluent ethyl acetate gradient
0%→12% in heptane) gave 19 (6.24g, 87%) as a colorless syrup: [ꢂ]D24 ꢃ44.3° (c
1.0, chloroform); lit.6 [ꢂ]D25 ꢃ44.7° (c 1.0, chloroform); 1H NMR (CDCl3) ꢄ 1.32,
1.33, 1.43, 1.53 [4s, 12H, 2 x C(CH3)2], 4.06 (m, 1H, H-5), 4.21 (dd, 1H, J3,4 ꢅ 8.0
Hz, H-3), 4.32 (dd, 1H, J2,3 ꢅ 2.4 Hz, H-2), 4.51 (ddd, 1H, J5,6 ꢅ 6.8 Hz, J6,6’ ꢅ
9.5 Hz, JF,6 ꢅ 48.2 Hz, H-6), 4.57 (ddd, 1H, J5,6’ ꢅ 5.5 Hz, JF,6’ ꢅ 46.1 Hz, H-6′),

ORDER
REPRINTS
42
BRACKHAGEN, BOYE, AND VOGEL
4.62 (ddd, 1H, J4,5 ꢅ 2.5 Hz, J4,F ꢅ 1.2 Hz, H-4), 5.53 (d, 1H, J1,2 ꢅ 4.9 Hz, H-1);
13C NMR (CDCl3) ꢄ 24.43, 24.90, 25.98 [2 x C(CH3)2 two signals are isochronic],
66.58 (d, JC,F ꢅ 22.9 Hz, C-5), 70.41, 70.49 (C-2,C-3), 70.56 (d, JC,F ꢅ 7.6 Hz, C-
4), 80.64 (d, JC,F ꢅ 168.1 Hz, C-6), 96.22 (C-1), 108.78, 109.44 [2 x C(CH3)2]; 19F
NMR (CDCl3) ꢄ -230.9.
Anal. Calcd for C12H19O5F (262.27): C, 54.95; H, 7.30. Found: C, 54.82; H,
7.18.
Successive Deisopropylidenation and Acetylation of 18 and 19. Compounds
18 (736 mg, 3.0 mmol) and 19 (787 mg, 3.0 mmol) were processed as described
for the syntheses of 12 and 13.
1,2,3,4-Tetra-O-acetyl-6-deoxy-ꢂ/ꢀ-L-(6-2H)-galactopyranose (20). (720
mg, 72%; ꢂ/ꢀ ratio 2.5:1; TLC solvent H Rf 0.20), colorless syrup: 1H NMR of the
ꢂ-anomer (CDCl3) ꢄ 1.09 (d, 2H, H-6, H-6′), 1.95, 1.96, 2.10, 2.13 (4s, 12H, 4 x
OCOCH3), 4.22 (t, 1H, J5,6 ꢅ J5,6′ ꢅ 6.4 Hz, H-5), 5.27-5.30 (m, 3H, H-2,H-3,H-
4), 6.28 (d, 1H, J1,2 ꢅ 2.8 Hz, H-1); 13C NMR of the ꢂ-anomer (CDCl3) ꢄ 15.55
(t, JC,D ꢅ 19.1 Hz, C-6), 20.42, 20.46, 20.52, 20.77 (4 x OCOCH3), 66.41 (C-2),
67.14 (C-5), 68.76 (C-3), 70.51 (C-4), 89.87 (C-1), 169.51, 170.32, 170.54, 170.91
(4 x OCOCH3); CI mass spectrum (isobutane): m/z 274 (C12H16O7Dꢃ, 98%], 153
[100%].
Anal. Calcd for C14H19O9D (333.31): C, 50.44. Found: C, 50.29.
1,2,3,4-Tetra-O-acetyl-6-deoxy-6-fluoro-ꢂ?ꢀ-L-galactopyranose (21). (883
mg, 84%; ꢂ/ꢀ ratio 3:1, TLC solvent H Rf 0.20), colorless syrup: 1H NMR of the
ꢂ-anomer (CDCl3) ꢄ 1,98, 2.01, 2.14, 2.15 (4s, 12H, 4 x OCOCH3), 4.25-4.40 (m,
2H, H-5,H-6,H-6’), 4.44 (dd, 0.5H, J5,6 ꢅ 5.3 Hz, J6,6’ ꢅ 9.3 Hz, H-6), 4.51 (dd,
0.5H, J5,6’ ꢅ 6.4 Hz,H-6’), 5.33-5.35 (m, 2H, H-2,H-3), 5.54 (s, 1H, H-4), 6.34 (d,
1H, J1,2 ꢅ 2.7 Hz, H-1); 13C NMR of the ꢂ-anomer (CDCl3) ꢄ?20.56, 20.59, 20.65,
20.89 (4 x OCOCH3), 66.38 (C-2), 67.28 (C-5), 67.45 (d, JC,F ꢅ 7.6 Hz, C-4),
69.52 (d, JC,F ꢅ 23.8 Hz, C-5), 81.10 (d, JC,F ꢅ 172.6 Hz, C-6), 89.64 (C-1),
169.20, 170.20, 170.37, 170.40 (4 x OCOCH3); 19F NMR of the ꢂ-anomer
(CDCl3) ꢄ?-231.6.
Anal. Calcd for C14H19O9F (350.30): C, 48.00; H, 5.46. Found: C, 47.79, H,
5.30.
ACKNOWLEDGMENTS
The authors are grateful to the Deutschen Forschungsgemeinschaft as well as
the Fonds der Chemischen Industrie for financial support.
REFERENCES
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Received June 28, 2000
Accepted November 9, 2000

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