Practical synthesis of D-[1-13C]mannose, L-[1-13C] and L-[6-13C]fucose

Article abstract of DOI:10.1016/j.tetlet.2004.11.073

The chemical synthesis of ¹³C-labeled mannose and fucose is important for the preparation of molecular probes used in the conformational study of the oligosaccharide portions of glycoproteins. A new method for the synthesis of the title [1-

Full text of DOI:10.1016/j.tetlet.2004.11.073

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 237–243
Practical synthesis of D-[1-13C]mannose,
L-[1-13C] and L-[6-13C]fucose
Ken-ichi Sato,* Shoji Akai, Hiroki Youda, Masaru Kojima, Mayumi Sakuma,
Shu-ichirou Inaba and Kyota Kurosawa
Laboratory of Organic Chemistry, Faculty of Engineering, Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku,
Yokohama 221-8686, Japan
Received 27 September 2004; revised 8 November 2004; accepted 12 November 2004
Abstract—The chemical synthesis of 13C-labeled mannose and fucose is important for the preparation of molecular probes used in
the conformational study of the oligosaccharide portions of glycoproteins. A new method for the synthesis of the title [1-13C]-labeled
compounds via the corresponding olefin compounds, which are in turn derived from D-mannitol or L-arabinose by efficient intro-
duction of 13C, by the Wittig reaction using Ph3P13CH3I and n-BuLi, is described. The introduction of 13CH3I to produce the
[1-13C]- and [6-13C]-labeled compounds was accomplished in 62%, 56%, and 71% yields, respectively. All mannose and fucose pro-
tons, from H-1 to H-6, were observed by the HMQC-TOCSY technique using 1:1 mixtures of [1-13C]- and [6-13C]-labeled
compounds.
Ó 2004 Elsevier Ltd. All rights reserved.
1. Introduction
for convenient observation of all protons of NeuAc
from H-3 to H-9 by the HMQC-HOHAHA technique.
We have also synthesized [3-13C]- and [9-13C]-labeled
NeuAc and demonstrated that identical results are ob-
tained by NMR for [3,9-13C]NeuAc as for 1:1 mixtures
of [3-13C] and [9-13C]NeuAc.5a This efficient method for
preparation of minimally 13C-labeled compounds has
enabled us to prepare practical amounts of important
13C-labeled monosaccharides, such as NeuAc, KDN,
galactose, mannose, mannosamine, and fucose for use
in the preparation of cell surface sialyl and KDN oligo-
saccharides. Labeled oligosaccharides are necessary
for the study of the interactions between these oligosac-
charides and the corresponding receptor molecules.
We previously reported5 a practical synthesis of mini-
mally 13C-labeled NeuAc, KDN, and galactose mono-
saccharides.
Sialyl glycoconjugates are important cell surface compo-
nents, active in a variety of intercellular recognition
events. Therefore, the study of the conformation and
dynamics of these sialyl oligosaccharides and their ana-
logues is necessary in order to gain insight into how
these cell surface oligosaccharides intact with the corre-
sponding receptor molecules. However, although the
conformational properties1–3 of low molecular weight
sialyl oligosaccharide analogues have been reported by
many research groups, the conformation and dynamics
of sialyl oligosaccharides and their analogues attached
to glycoproteins have not yet been fully analyzed. To ad-
dress this problem, 13C-labeled sialic acid (NeuAc) has
been utilized for the conformational analysis of sialyl
oligosaccharides on artificial membrane surfaces4 and
by TRNOE experiments.4 Recently, a novel NMR tech-
nique, HSQC-TOCSY-NOESY-TOCSY, for observa-
tion of all protons of glycoprotein NeuAc, H-3 to H-9,
even with only a single 13C-labeled atom (3-position),
has been reported.2 However, since combined multi-
pulse techniques generally suffer from low sensitivity,
we have synthesized minimally labeled [3,9-13C]NeuAc
In this letter, the practical syntheses of D-[1-13C]-
mannose, L-[1-13C]fucose, and L-[6-13C]fucose are
described. 13C is preferably introduced at the last stage,
thereby preserving as much labeled compound as possi-
ble, in a strategy analogous to that reported previously.
As
a
13C source, commercially available 13CH3I
was used and the introduction of 13C was performed
by extension of either the terminal head or end of the
precursor with labeled reagents derived from 13CH3I.
D-[6-13C]Mannose has already been synthesized
Keywords: Carbohydrates; Labeling; NMR.
*
Corresponding author. Tel.: +81 45 481 5661x3853; fax: +81 45 413
9770; e-mail: satouk01@kanagawa-u.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.11.073

238
K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
efficiently in previous studies.5 The synthesis of L-
[6-13C]fucose was achieved using a similar procedure
to that for the unlabeled compound.6 The labeling effect
of a 1:1 mixture of these monosaccharides by the
HMQC-TOCSY technique was also examined.
0.01 equiv) in t-BuOH at rt for 5 h gave a mixture of
the syrupy diol compounds 610 and 7, which were puri-
fied on a column of silica gel (ethyl acetate/hexane =
2:3), in 71% and 23% yields, respectively. Another effort
to obtain the 2,3,4,5-tetra-O-benzyl derivative of 4 from
D-arabinose was also made, but the oxidation products
of the corresponding enitol derivative of 5 could not
be separated.
2. Synthesis of D-[1-13C]mannose from D-mannitol
D-[1-13C]Mannose was synthesized from D-mannitol as
follows (Scheme 1). 1,2:3,4-Di-O-isopropylidene-D-man-
nitol (1) was synthesized by InchÕs method.7 Compound
1 was treated with sodium hydride (2.5 equiv) and benz-
yl bromide (2.2 equiv) in DMF at 0 °C to give the syr-
upy benzyl derivative 210 in 88% yield, which was
purified on a column of silica gel (ethyl acetate/hex-
ane = 1:8). Compound 2 was then treated with 90%
aqueous acetic acid at room temperature (rt) for 11 h
to give the partially hydrolyzed syrupy derivative 310
in 85% yield. The structure of 3 was confirmed by prep-
aration of the corresponding 1,2-di-O-acetyl derivative.
Compound 3 was then treated with sodium metaperio-
date (2.0 equiv) in methanol until disappearance of 3
to give the corresponding syrupy degradation product,
4,5-di-O-benzyl-2,3-O-isopropylidene-D-arabinose (4)
[1H NMR (500 MHz, CDCl3): d 9.68 ppm, doublet,
J = 1.7 Hz, –CHO] quantitatively. After azeotropic re-
moval of water from 4 with toluene, the Wittig reaction
of 4 with Ph3P13CH3I (1.0 equiv) and n-BuLi in hexane
(2.44 M, 1.0 equiv) in dry THF at ꢀ30 °C gave the
syrupy arabino-hex-1-[1-13C]enitol (5),10 which was puri-
fied on a column of silica gel (ethyl acetate/hexane = 1:8)
in 80% yield. The 13C-labeled phosphonium salt
Ph3P13CH3I was conveniently synthesized using
13CH3I and PPh3 in toluene in almost quantitative yield.
Oxidation of 5 with 4-methylmorphorine N-oxide
(NMO, 2.0 equiv) and OsO4 (t-BuOH solution,
For the transformation to mannose, selective oxidation
of the primary OH of the D-mannitol derivative 6
with trichloroisocyanuric acid (TCCA, 1.1 equiv) and
2,2,6,6-tetramethyl-1-piperidinyloxy radical8 (TEMPO,
0.01 equiv) in CH2Cl2 at 0 °C for 2 h gave the corre-
sponding aldehyde derivative in good yield. The alde-
hyde derivative was then treated with 10% Pd–C
and H2 in EtOH, followed by acid hydrolysis with
Dowex H+ in H2O at 50 °C to give the required
D-[1-13C]mannose. The yield of D-[1-13C]mannose
from 6 (three steps) was 89%. The structure of 13C-
labeled D-[1-13C]-mannose was confirmed by compari-
son of the NMR data with that of non-labeled mannose.
NMR data for the non-labeled and the 13C-labeled man-
nose are shown in Figure 1. The undesired D-glucitol
derivative 7 can be converted into 6 as follows: com-
pound 7 was treated with benzoyl chloride (1.1 equiv)
in pyridine at 0 °C until disappearance of the starting
material, followed by mesylation with methanesulfonyl
chloride (2.0 equiv) to give the corresponding syrupy
derivative 8,10 followed by separation on a column of
silica gel (ethyl acetate/hexane = 1:4), in 90% yield.
Compound 8 was then treated with a solution of KOH
(3.0 equiv) in MeOH for 3 h at rt to give the syrupy
1,2-epoxy derivative 9,10 which was purified on a column
of silica gel (ethyl acetate/hexane = 1:3), in 88% yield.
The epoxy derivative 9 was hydrolyzed with 1 M KOH
in DMSO at 70 °C for 6 h to give 6, which was purified
OH
OBn
OH
O
HO
O
BnO
HO
O
c)
a)
b)
Ref. 7
O
O
D-Mannitol
O
O
O
O
O
O
O
O
y. quant.
2 steps
y. 88 %
y. 85 %
OBn
OBn
OBn
OBn
1
2
6
3
4
13C
OH
HO
HO
OH
O
HO
i)
O
13C
HO
O
y. 89 %
(3 steps)
OH
y. 71%
e)
OBn
OBn
13CH2
D
-[1-13C]Mannose
d)
O
h)
O
y. 80 %
OBn
OBn
y. 90%
y. 23%
13C
13C
13C
OH
OH
OBz
OMs
5
O
f)
g)
O
O
O
O
O
O
y. 90%
y. 88%
OBn
OBn
OBn
OBn
OBn
OBn
7
8
9
Scheme 1. Reagents and conditions: (a) BnBr, NaH/DMF; (b) 90% AcOH aq, (c) NaIO4/MeOH–H2O; (d) Ph3P13CH3I, n-BuLi/THF; (e) OsO4,
NMO/t-BuOH–H2O; (f) BzCl, Py then MsCl; (g) KOH/MeOH; (h) 1 M KOH/DMSO; (i) i. TEMPO, TCCA/CH2Cl2, ii. 10% Pd–C, H2/EtOH, iii.
Dowex H+/H2O.

K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
239
Figure 1. 1H NMR spectra of non-labeled and 13C-labeled D-mannoses.
on a column of silica gel (ethyl acetate/hexane = 1:3), in
90% yield. These procedures result in 62% utilization of
13CH3I in this D-[1-13C]mannose synthesis.
1110 in 83% yield. Compound 11 was treated with tri-
phenylmethyl chloride (1.2 equiv) in pyridine at 55 °C
for 1 h to give the trityl derivative 1210 in 90% yield.
To a solution of 12 and NaH (3.3 equiv) in DMF, ben-
zyl bromide (3.3 equiv) was added dropwise at 0 °C and
quenched with NaOMe in methanol to give 1310 in 95%
yield. Compound 13 was then hydrolyzed in 90% aq ace-
tic acid at 50 °C for 30 min to give the syrupy compound
1410 [purified on a column of silica gel, (ethyl acetate/
hexane = 1:5)] in 95% yield. The primary hydroxyl
group of the product was then selectively oxidized with
TCCA (1.2 equiv) and TEMPO (0.01 equiv) in CH2Cl2
at 0 °C to give the syrupy 5-deoxy-L-lyxo derivative
1510 [purified on a column of silica gel, (ethyl acetate/
hexane = 1:5)] quantitatively. Wittig reaction of 15 with
Ph3P13CH3I (1.0 equiv) and n-BuLi in hexane (2.44 M,
1.0 equiv) in dry THF at ꢀ20 °C gave the syrupy
L-lyxo-hex-1-[1-13C]enitol (16)10 [purified on a column
of silica gel, (ethyl acetate/hexane = 1:12)] in 71% yield.
Oxidation of 16 with NMO (2.0 equiv) and OsO4
(t-BuOH solution, 0.01 equiv) in t-BuOH/H2O (1:1) at
0 °C until the disappearance of 16 gave a mixture of
the syrupy diol compounds 1710 and 18,10 which were
purified on a column of silica gel (ethyl acetate/hex-
ane = 1:2), in 9% and 88% yields, respectively. For
transformation into fucose, the primary OH of 6-
deoxy-L-galactitol derivative 17 was selectivity oxidized
with TCCA (1.1 equiv) and TEMPO8 (0.01 equiv) in
CH2Cl2 at 0 °C for 30 min to give the corresponding
3. Synthesis of D-[6-13C]mannose from D-mannose
We have already reported a convenient chemoenzymatic
synthesis of [3,9-13C]-labeled NeuAc and KDN using
D-[6-13C]mannose.5a In that work, D-[6-13C]mannose
was synthesized via the benzyl 2,3-O-isopropylidene-a-
D-mannofuranoside for use as an intermediate in labeled
KDN syntheses. The utilization of 13CH3I in the synthe-
sis of D-[6-13C]mannose from D-mannose was 54%.
NMR data for each 13C-labeled mannose are given in
Ref. 6. HMQC-TOCSY spectra of the 1:1 mixture of
methyl a-D-[1-13C] and [6-13C]mannopyranoside is
shown in Figure 2. It is easy to analyze the chemical
shifts and J values of all protons using this technique.
4. Synthesis of L-[1-13C]fucose from L-arabinose
This compound was synthesized from L-arabinose as
shown in Scheme 2. The reaction of L-arabinose and eth-
ane thiol (4.0 equiv) in 12 M HCl at 0 °C gave the corre-
sponding diethyl dithioacetal 1010 in 87% yield.
Reduction of 10 with Raney Ni in 70% aq ethanol solu-
tion under reflux conditions gave the deoxy derivative

240
K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
Figure 2. HMQC-TOCSY spectra of a 1:1 mixture of methyl a-D-[1-13C] and [6-13C]mannopyranoside.
EtS
SEt
OH
CH3
OH
CH3
OH
CH3
OBn
CH3
OBn
a)
b)
c)
d)
e)
L
-Arabinose
HO
HO
HO
HO
HO
HO
BnO
BnO
BnO
BnO
y. 87%
y. 83%
y. 90%
y. 95%
y. 95%
OH
OH
OTr
OTr
OH
10
11
12
13
14
13C OH
13CHO
OH
13C
HO
HO
f)
i)
H3C
HO
O
OBn
OBn
OBn
OBn
OH
OH
y. quant.
y. 92%
BnO
BnO
y. 9%
13CH2
L
-[1-13C]Fucose
CH3
CH3
CHO
f)
y. quant.
g)
y. 71%
h)
OBn
OBn
17
19
OBn
OBn
l)
BnO
y. 96%
BnO
CH3
15
13C
CH3
y. 88%
13C
13C
OBz
OH
OH
OBn
OBn
O
16
OMs
OBn
OBn
j)
y. 96%
k)
OBn
OBn
y. 96%
BnO
BnO
BnO
CH3
CH3
CH3
18
20
21
Scheme 2. Reagents and conditions: (a) EtSH, 12 M HCl; (b) Raney Ni/70% EtOH aq; (c) TrCl, Py; (d) NaH, BnBr/DMF; (e) 90% AcOH aq;
(f) TEMPO, TCCA/CH2Cl2; (g) Ph3P13CH3I, n-BuLi/THF; (h) OsO4, NMO/t-BuOH–H2O; (i) 10% Pd–C, H2/EtOH–H2O; (j) BzCl, Py then MsCl;
(k) 1 M KOH/MeOH; (l) 1 M KOH/DMSO.
syrupy aldehyde derivative 1910 [IR: mC@O 1671 cmꢀ1
,
KOH in MeOH (1.0 M, 3.0 equiv) at 40 °C and the reac-
tion was monitored by TLC (acetone/toluene = 1:20) to
give the syrupy 1,2-epoxy derivative 2110 [purified on a
column of silica gel, (ethyl acetate/hexane = 1:10)] in
96% yield. The epoxy derivative 21 was then hydrolyzed
with 1 M KOH in DMSO at 70 °C to give 17 in 96%
yield. This method results in 56% utilization of 13CH3I
in the preparation of L-[1-13C]fucose.
purified on a column of silica gel (ethyl acetate/
hexane = 1:2)] in 92% yield. The product 19 was then
treated with Pd–C/H2 at rt to give 13C-labeled
L-fucose quantitatively. The structure of L-[1-13C]fucose
was confirmed by comparison of the NMR data with
those of non-labeled fucose. The NMR data for non-
labeled fucose and the 13C-labeled fucose are shown in
Figure 3. The undesired L-talitol derivative 18 was trans-
formed into 2010 [purified on a column of silica gel,
(acetone/toluene = 1:20)] by reaction with benzoyl
chloride (1.2 equiv) in pyridine at 0 °C, followed by
mesylation with methanesulfonyl chloride (1.5 equiv)
in 96% yield. Compound 20 was then treated with
5. Synthesis of L-[6-13C]fucose from D-mannose
L-[6-13C]Fucose was prepared according to the method
described by Petit et al. (Scheme 3). Therefore, here we

K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
241
Figure 3. 1H NMR spectra of non-labeled and 13C-labeled L-fucoses.
13CH3
with dimethoxypropane in the presence of a catalytic
amount of p-toluenesulfonic acid in acetone to give the
di-O-isopropylidene derivative 22 in 73% yield. A reac-
tion mixture of 22 and 13CH3Li (1.14 M in THF,
3.0 equiv, prepared from 13CH3I and lithium quantita-
tively) in THF was stirred at ꢀ50 °C and the tempera-
ture was allowed to rise to 0 °C gradually within 5 h
and then to rt for another 2 h under argon to give the
corresponding syrupy 13C-labeled heptitol derivative
2310 [purified on a column of silica gel, (acetone/tolu-
ene = 1:4)] in 94% yield. The structure of 23 was con-
firmed using NMR by preparation of the acetyl
derivative 230.10 Compound 23 was treated with NaH
(3.0 equiv) and benzyl bromide (2.5 equiv) in DMF at
0 °C and the temperature was allowed to rise to rt to
give the syrupy di-O-benzyl derivative 24 [purified on a
column of silica gel, (ethyl acetate/hexane = 1:9)] in
88% yield. Compound 24 was treated in 70% aq acetic
acid solution at 50 °C to give the de-isopropylidene
derivative 2510 quantitatively. The product of 25 was
treated with an aq NaIO4 solution in MeOH at 0 °C
O
OR
O
a)
b)
O
O
O
OH
D-Mannose
O
O
y. 73%
y. 94%
OR
O
O
c)
22
23 : R= H
y. quant.
23': R= Ac
13CH3
13CH3
OBn
OBn
d)
e)
O
HO
HO
O
y. quant.
y. 88%
OBn
O
OBn
OH
O
OH
25
24
13CH3
OH
OH
OBn
O
f)
g)
H313C
O
OH
BnO
OH
y. quant.
y. 86%
HO
-[6-13C]Fucose
L
OH
26
to give
a
syrupy mixture of 2,5-di-O-benzyl-L-
Scheme 3. Reagents and conditions: (a) (CH3)2C(OCH3)2, p-TsOH/
acetone; (b) 13CH3Li/THF; (c) Ac2O, Py; (d) NaH, BnBr/DMF;
(e) 70% AcOH aq; (f) NaIO4/MeOH–H2O; (g) 10% Pd(OH)2–C,
H2/EtOH.
[6-13C]fucofuranose (a and b) 2610 [purified on a column
of silica gel, (ethyl acetate/hexane = 1:1)] in 86% yield.
Finally, catalytic reduction of 26 with 10% Pd(OH)2–
C/H2 in EtOH at 35 °C gave the desired L-[6-13C]fucose
quantitatively. The structure of L-[6-13C]fucose was con-
firmed by comparison of the NMR data with those for
the non-labeled fucose. This method results in 71%
only briefly describe the synthesis of the 13C-labeled
compound from D-mannose. D-Mannose was treated

242
K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
Figure 4. HMQC-TOCSY spectra of a 1:1 mixture of phenyl 1-thio-b-L-[1-13C] and [6-13C]fucopyranoside.
utilization of 13CH3I in this synthesis of L-[6-13C]fucose.
The NMR data for non-labeled fucose and the 13C-la-
beled fucose are shown in Figure 3. NMR data for each
13C-labeled fucose are given in Ref. 9. The HMQC-
TOCSY spectra of the 1:1 mixture of phenyl 1-thio-b-
L-[1-13C] and [6-13C]fucopyranoside is shown in Figure
4. Using this technique enabled us to determine the
chemical shifts and J values of all protons.
Ng, K. K.-S.; Weis, W. I. Biochemistry 1997, 36, 979–988;
(c) Henrichsen, D.; Ernst, B.; Magnani, J. L.; Wang,
W.-T.; Meyer, B.; Peters, T. Angew. Chem., Int. Ed. 1999,
38, 98–102; (d) Homans, S. W. Biochem. Soc. Trans. 1998,
26, 551–560.
4. (a) Aubin, Y.; Prestegard, J. H. Biochemistry 1993, 32,
3422–3428; (b) Salvatore, B. A.; Ghose, R.; Prestegard, J.
H. J. Am. Chem. Soc. 1996, 118, 4001–4008.
5. (a) Sato, K.; Akai, S.; Hiroshima, T.; Aoki, H.; Sakuma,
M.; Suzuki, K. Tetrahedron Lett. 2003, 44, 3513–3516; (b)
Sato, K.; Akai, S.; Sakuma, M.; Kojima, M.; Suzuki, K.
Tetrahedron Lett. 2003, 44, 4903–4907.
6. Gesson, J. P.; Jacquesy, J. C.; Petit, P. Tetrahedron Lett.
1992, 104, 3637–3640.
7. Inch, T. D.; Rich, P. J. Chem., Soc. Sect. C 1968, 13,
1683–1692.
As described above, a practical synthesis of minimally
13C-labeled D-mannose and L-fucose should facilitate
studies on the conformational properties and dynamic
behavior of oligosaccharides that contain mannose and
fucose. This short and efficient 13C-labeling method
should also be applicable for 14C-labeling, facilitating
the preparation of labeled oligosaccharides for reaction
with the corresponding receptor molecules in order to
determine the interaction mechanisms.
8. Luca, L. D.; Giacomelli, G.; Porcheddu, A. J. Org. Chem.
1975, 40, 2764–2769.
9. 1H and 13C NMR data of 13C-labeled mannose and
fucose.
1
D-[1-13C]mannose: H NMR (500 MHz, D2O): d 5.03 (1H,
dd, J1,2 = 1.4 Hz, J1,C = 170.4 Hz, H-1a), 4.75 (1H, dd,
J1,2 = 1.0 Hz, J1,C = 160.5 Hz, H-1b), 3.78 (1H, dd,
J2,3 = 3.3 Hz, H-2b), 3.78 (1H, dd, J2,3 = 3.3 Hz, H-2a),
Acknowledgements
0
This work was partially supported by a ÔHigh-Tech
Research Center ProjectÕ and
(15750148) for Scientific Research from the Ministry
of Education, Science, Sports and Culture, Japan. The
author thanks Professor T. Nakagawa for helpful
discussions.
3.76 (1H, dd, J6,5 = 2.3 Hz, J6;6 ¼ 12:3 Hz, H-6b), 3.73
0
(1H, dd, J6,5 = 2.1 Hz, J6;6 ¼ 12:0 Hz, H-6a), 3.70 (1H, dd,
a
Grant-in-Aid
J3,4 = 9.9 Hz, H-3a), 3.67 (1H, dddd, J5,4 = 9.7 Hz,
J5;6 ¼ 5:9 Hz, J5,C = 1.3 Hz, H-5), 3.61 (1H, dd, H-60a),
0
3.58 (1H, dd, J6 ;5 ¼ 6:3 Hz, H-60b), 3.51 (1H, dd, H-4a),
0
3.51 (1H, dd, J3,4 = 9.7 Hz, H-3b), 3.42 (1H, dd,
J4,5 = 9.7 Hz, H-4b), 3.23 (1H, dddd, J5,C = 2.1 Hz, H-5b);
13C NMR (125 MHz, D2O):
d 94.02 (C-1a), 93.66
(C-1b).
D-[6-13C]mannose: 1H NMR (500 MHz, D2O): d 5.06 (1H,
dd, J1,2 = 1.7 Hz, H-1a), 4.75 (1H, dd, J1,2 = 0.9 Hz, H-1b),
References and notes
1. Miyazaki, T.; Sakakibara, T.; Sato, H.; Kajihara, Y.
J. Am. Chem. Soc. 1999, 121, 1411–1412.
2. Miyazaki, T.; Sato, H.; Sakakibara, T.; Kajihara, Y. J.
Am. Chem. Soc. 2000, 122, 5678–5694. See also references
cited therein.
3.82 (1H, dd, J2,3 = 3.3 Hz, H-2b), 3.81 (1H, dd, J2,3
=
0
3.4 Hz, H-2a), 3.78 (1H, dd, J6,5 = 2.2 Hz, J6;6 ¼ 12:2 Hz,
J6,C = 144.3 Hz, H-6b), 3.73 (1H, dd, J6,5 = 2.2 Hz,
0
J6;6 ¼ 12:2 Hz, J6,C = 144.0 Hz, H-6a), 3.73 (1H, dd,
J3,4 = 9.6 Hz, H-3a), 3.70 (1H, ddd, J5,4 = 10.0 Hz,
3. (a) Weis, W.; Brown, J. H.; Cusack, S.; Paulson, J. C.;
Skehel, J. J.; Wiely, D. C. Nature 1988, 333, 426–431; (b)
0
0
J5;6 ¼ 5:8 Hz, H-5a), 3.64 (1H, ddd, J6 ;C ¼ 143:0 Hz, H-
60a), 3.60 (1H, ddd, J6 ;5 ¼ 6:0 Hz, J6 ;C ¼ 120:8 Hz, H-
0
0

K. Sato et al. / Tetrahedron Letters 46 (2005) 237–243
243
60b), 3.54 (1H, ddd, J4,C = 3.6 Hz, H-4a), 3.52 (1H, dd,
J3,4 = 9.8 Hz, H-3b), 3.46 (1H, ddd, J4,5 = 9.7 Hz,
J4,C = 3.6 Hz, H-4b), 3.26 (1H, dddd, J5,C = 2.2 Hz, H-
5b); 13C NMR (125 MHz, D2O): d 62.01 (C-6b), 62.00 (C-
6a).
10. Physical data ([a]D and mp) of synthesized compounds.
26
Compound 2: ½aꢁD +8.9 (c 1.1, CHCl3); compound 3:
26
26
26
½aꢁD ꢀ18.3 (c 1.0, CHCl3); compound 5: ½aꢁD +1.9 (c 1.0,
26
CHCl3); compound 6: ½aꢁD ꢀ19.4 (c 1.2, CHCl3);
compound 7: ½aꢁD ꢀ9.2 (c 1.1, CHCl3); compound 8:
26
26
L-[1-13C]fucose: 1H NMR (600 MHz, D2O): d 5.05 (1H, dd,
½aꢁD ꢀ17.1 (c 1.1, CHCl3); compound 9: ½aꢁD ꢀ1.3 (c 1.3,
CHCl3); compound 10: mp 127.0–128.7 °C, (recrystallized
from ethanol); compound 11: mp 131.5–132.3 °C, (recrys-
tallized from ethanol–hexane); compound 12: mp 89.8–
90.7 °C, (recrystallized from ethanol–hexane); compound
13: mp 94.3–95.2 °C, (recrystallized from ethyl acetate–
J1,2 = 4.0 Hz, J1,C = 168.9 Hz, H-1a), 4.40 (1H, d, J1,2
=
7.9 Hz, J1,C = 160.5 Hz, H-1b), 4.05 (1H, q, J5,6 = 6.5 Hz,
H-5a), 3.71 (1H, dd, J3,2 = 10.3 Hz, J3,4 = 3.3 Hz, H-3a),
3.66 (1H, d, H-4a), 3.66 (1H, dq, J5,6 = 6.5 Hz,
J5,C = 2.4 Hz, H-5b), 3.62 (1H, dd, H-2a), 3.60 (1H, d,
J4,3 = 3.4 Hz, H-4b), 3.49 (1H, ddd, J3,2 = 10.0 Hz,
J3,C = 1.2 Hz, H-3b), 3.30 (1H, ddd, J2,C = 7.9 Hz, H-2b),
1.10 (3H, d, H-6b), 1.06 (3H, d, H-6a); 13C NMR (150 MHz,
D2O): d 96.24 (C-1b), 92.22 (C-1a).
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hexane); compound 14: ½aꢁD +11.6 (c 1.1, CH3OH);
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compound 15: ½aꢁD +24.3 (c 1.0, CHCl3); compound 16:
25
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½aꢁD +26.6 (c 1.0, CH3OH); compound 17: ½aꢁD ꢀ15.8
(c 1.0, CHCl3); mp 75.0–76.0 °C, (recrystallized from ethyl
24
L-[6-13C]fucose: 1H NMR (500 MHz, D2O): d 5.08 (1H, d,
J1,2 = 3.7 Hz, H-1a), 4.44 (1H, d, J1,2 = 7.9 Hz, H-1b), 4.09
(1H, dq, J5,6 = 6.7 Hz, J5,C = 3.1 Hz, H-5a), 3.75 (1H, dd,
J3,2 = 10.4 Hz, J3,4 = 3.4 Hz, H-3a), 3.69 (1H, dq,
J5,6 = 6.7 Hz, J5,C = 3.3 Hz, H-5b), 3.66 (1H, d, H-4a),
3.65 (1H, dd, H-2a), 3.63 (1H, d, J4,3 = 3.7 Hz, H-4b), 3.52
(1H, dd, J3,2 = 10.1 Hz, H-3b), 3.34 (1H, dd, H-2b), 1.13
(3H, dd, J6,C = 127.6 Hz, H-6b), 1.09 (3H, dd,
J6,C = 127.3 Hz, H-6a); 13C NMR (125 MHz, D2O): d
15.63 (C-6a), 16.76 (C-6b).
acetate–hexane); compound 18: ½aꢁD ꢀ10.7 (c 0.8, CHCl3);
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compound 20: ½aꢁD ꢀ36.0 (c 1.1, CHCl3); mp 78.9–
25
81.2 °C, (recrystallized from ethyl acetate–hexane); com-
pound 21: ½aꢁD +18.3 (c 1.0, CHCl3); compound 23:
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28
½aꢁD +64.2 (c 0.3, CHCl3); compound 230: ½aꢁD ꢀ11.3
26
(c 1.0, CHCl3); mp 73.5–75.0 °C, (recrystallized from
ethanol–hexane); compound 24: ½aꢁD ꢀ2.5 (c 1.1, CHCl3);
22
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compound 25: ½aꢁD +26.7 (c 1.1, CHCl3); mp 99.5–101 °C,
(recrystallized from ethanol–hexane); compound 26: ½aꢁD
+13.9 (c 0.6, CHCl3).