Synthesis of N-protected azaoligosaccharides and their cyclic derivatives

Article abstract of DOI:10.1016/j.tetlet.2005.02.057

Azaoligosaccharides are prepared through the glycosylation of nojirimycin derivatives with catalytic amounts of TMSOTf. Also, the 1-6′, 1′-6-cyclic azadisaccharides are successfully synthesized, and their one-pot syntheses are demonstrated.

Full text of DOI:10.1016/j.tetlet.2005.02.057

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2399–2403
Synthesis of N-protected azaoligosaccharides and their
cyclic derivatives
Daisuke Sawada,a Hideyo Takahashi,a Moto Shirob and Shiro Ikegamia,*
aFaculty of Pharmaceutical Sciences, Teikyo University, Sagamiko Kanagawa 199-0195, Japan
bRigaku Corporation, 3-9-12 Matsubara, Akishima, Tokyo 196-0003, Japan
Received 17 January 2005; revised 31 January 2005; accepted 10 February 2005
Abstract—Azaoligosaccharides are prepared through the glycosylation of nojirimycin derivatives with catalytic amounts of
TMSOTf. Also, the 1-60, 10-6-cyclic azadisaccharides are successfully synthesized, and their one-pot syntheses are demonstrated.
Ó 2005 Elsevier Ltd. All rights reserved.
Table 1. Glycosylation of 1 and 2 or 3
It is well-known that sugars play an important role in
OBn
Boc
OBn
Boc
human life, and recently, functional oligosaccharides
are much of interest. Azasugars, on the other hand,
are rare natural products such as nojirimycin,1 and a
large number of their derivatives has been reported.2
In those cases, researchers focused on mono-azasugars,
and directed their interest mainly to glycosidase-inhibi-
tory activities.3 As a result, few research efforts have
been made on azaoligosaccharide chemistry and limited
examples of oligosaccharides containing azasugars have
been reported.4–7 Azasugars, however, have interesting
properties, which are not possessed by sugars. First,
azasugars are able to make a covalent bond from the
ring-nitrogen to the outside of the sugar ring. By this un-
ique bond, azaoligosaccharides are expected to have
various structures and new functions. Secondly, a hy-
droxyl group at an anomeric carbon of an azasugar is
so reactive that elongation of the azasugar chains will
be easier than that of sugar chains. Here we report the
synthesis of azaoligosaccharides and their cyclic com-
pounds using their unique properties.
promoter
N
N
BnO
BnO
BnO
BnO
R'OH (2 or 3)
(1.2 eq)
BnO
4, 5
BnO
OH
OR'
THF
1
Run
Acceptor
Promoter (equiv)
Temp. (°C)
% Yield
(4 or 5)
1
2
3
4
5
6
2
2
2
3
3
3
TsOHÆH2O (1)
La(OTf)3 (1)
TMSOTf (0.5)
La(OTf)3 (5)
TMSOTf (1)
TMSOTf (0.5)
rt
10
72
89
29
40
86
0
À78
rt
0
À40
Boc: t-butoxycarbonyl; 2, 4: R0 = cyclohexyl; 3, 5: = BnO
O
BnO
BnO
OMe
9
careful investigation of the promoters, La(OTf)3 and
TMSOTf10 were found to be more effective in this reac-
tion. Besides, the azasugars are so reactive that it is not
necessary to convert the hydroxyl group at the anomeric
carbons to more active leaving groups. Next, we investi-
gated the synthesis of a disaccharide using the sugar
derivative(3) as an acceptor with La(OTf)3 and
TMSOTf. The reaction of the azasugar 1 and 3 with
La(OTf)3 was less reactive, resulting in 29% yield of
the product 5 even using excess amounts of the pro-
moter. By using TMSOTf, the starting material 1 rapi-
dly disappeared, and the reaction afforded 40% of 5 at
0 °C accompanied by many by-products. Therefore,
the reaction was carried at À40 °C with 0.5 equiv of
TMSOTf to give 5 in 86% yield. The products 4 and 5
In the first place, we optimized the conditions of glyco-
sylation with the known azasugar 18 as a donor and
cyclohexanol (2) as an acceptor (Table 1). According
to Vasellaꢀs report,8 the reaction of 1 and 2 in THF
was examined using TsOHÆH2O as a promoter, and
afforded the desired product 4 only in 10% yield, and
by-products were derived from both 1 and 4. After
Keywords: Amino sugars; Dimeric cycloazasugar; Azaoligosaccharide.
*
Corresponding author. Tel.: +81 426853728; fax: +81 426851870;
e-mail: shi-ike@pharm.teikyo-u.ac.jp
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.02.057

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D. Sawada et al. / Tetrahedron Letters 46 (2005) 2399–2403
Table 2. Synthesis of an azadisaccharide
OMPM
OMPM
Boc
Boc
OR2
NH
N
N
OMPM
BnO
BnO
BnO
BnO
BnO
Boc
b
a
N
BnO
BnO
BnO
BnO
BnO
OMPM
BnO
O
O
BnO
O
Boc
H
N
BnO
7 : R2=H
Boc
BnO
BnO
O
N
N
BnO
BnO
9 : R2=TMS
promoter
THF
BnO
BnO
6 : R1 = H
8 : R1 = TMS
OR1
NH
BnO
11
BnO
BnO
BnO
10
BnO
O
O
10
O
OMPM
Boc
OMPM
Boc
N
N
BnO
BnO
BnO
Run Donor Acceptor Promoter
(equiv)
Temp.
(°C)
% Yield
(10)
BnO
c
(equiv)
BnO
BnO
O
O
1
2
3
4
5
6
7
8
6
6
6
8
8
8
8
8
7 (2)
7 (1.2)
7 (2)
7 (2)
9 (2)
9 (2)
9 (2)
9 (3)
La(OTf)3 (1)
TMSOTf (0.5)
TMSOTf (0.5)
0 to rt
0
60
71
47
52
75
Boc
OH
Boc
N
N
BnO
BnO
BnO
BnO
0
0
12
13
BnO
BnO
OTMS
TMSOTf (0.5) À40
TMSOTf (0.5)
Scheme 1. Reagents and conditions: (a) (Boc)2O, DMAP, CH3CN;
92%; (b) NaBH4, MeOH; 100%; (c) TMSCl, imidazole, DMF; 100%.
0
TMSOTf (0.5) À40
TMSOTf (0.2) À78 to À40 90a
TMSOTf (0.5) À40
53
a A stereoisomer was obtained in 2% yield.
Table 3. Synthesis of an azatrisaccharide
OMPM
Boc
N
OMPM
BnO
BnO
Boc
N
BnO
BnO
BnO
were obtained as a single stereoisomer irrespective of the
stereochemistry at the anomeric carbon of the starting
materials.
O
7 or 9
BnO
Boc
N
O
BnO
BnO
TMSOTf
Boc (0.5eq)
BnO
N
BnO
BnO
O
THF
OR1
To synthesize an azadisaccharide, we investigated the
reaction using the azasugar 711 as an acceptor (Table
2). With La(OTf)3, the reaction of 611 and 7 did not pro-
ceed due to the strong coordination with La(OTf)3 by
the amide moiety of 7. Using TMSOTf, we could obtain
the corresponding azadisaccharide 10 in 60% yield by
using 1.2equiv of 7, and in 71% yield by using 2equiv
of 7 at 0 °C. Next, compounds 8 and 9 with the hydroxyl
groups protected as TMS ethers, were prepared for fur-
ther examination of this glycosylation.12 Fortunately,
the reaction of 8 and 9 smoothly proceeded and 10
was obtained in 52% yield though some decomposition
of the compounds still occurred. Then, the reaction at
lower temperature gave a better result (75% yield at
À40 °C, run 6). Finally, after the addition of 0.2equiv
of TMSOTf at À78 °C, the mixture was reacted at
À40 °C, and this reaction afforded the azadisaccharide
10 in 90% yield (run 7).13
BnO
NH
BnO
BnO
12 : R1=H
13 : R1=TMS
14
O
BnO
Run Acceptor Donor (equiv) Temp. (°C) % Yield of 14
1
2
3
12
13
13
7 (2)
9 (2)
9 (2)
0
0 (10: 52 )
À78 to À40 41 (10: 43)
À78 to À60 41 (10: 18)
a similar route in Scheme 1, we prepared the starting
substrate for the cyclization reaction. Removal of the
MPM group of 11 by DDQ oxidation (86%) and reduc-
tion by NaBH4 afforded the dihydroxyl compound
(95%), which was converted to di-TMS ether 15
(100%). Using this compound, the cyclization was exam-
ined (Table 4). Compound 15 was reacted with TMSOTf
at À40 °C, and the cyclic compound 16, which shows a
1
complex asymmetric H NMR due to the steric repul-
Further elongation of the azadisaccharide 10 was exam-
ined. As shown in Scheme 1, the amide nitrogen of 10
was protected by a Boc group, and the subsequent
reduction by NaBH4 afforded 12, which was converted
to TMS ether 13. Using 12 or 13 as a donor, we tried
to synthesize an azatrisaccharide under the above glycos-
ylation conditions (Table 3). With 0.5 equiv of
TMSOTf, 12 and 7 were reacted at 0 °C in THF to give
the unexpected azadisaccharide 1014 instead of the de-
sired azatrisaccharide 14. The reaction of 13 and 9 at
À78 °C to À40 °C, however, afforded 14 in 41% yield
as a single stereoisomer, although the azadisaccharide
10 was still obtained in 43% yield. The same reaction
at À78 °C to À60 °C gave 14 in 41% yield, 10 in 18%
yield, and recovery of starting material (30%).
Table 4. Synthesis of cyclic azaoligosaccharides
Boc
Boc
N
N
H
H
OTMS
Boc
O
O
N
H
OBn
H
OBn
OBn
BnO
BnO
BnO
BnO
BnO
O
16
promoter
BnO
O
+
THF
Boc
N
BnO
BnO
BnO
BnO
17
Boc
15
BnO
N
BnO
OTMS
Run
Promoter (equiv)
TMSOTf (0.5)
Temp. (°C)
À40
% Yield of 16
1
2TMSOTf (0.5)
10
À78 to À50
À78 to À50
À78
60 (17: 42a)
37 (17: 57a)
24 (17: 35a)
3
4
TBSOTf (0.5)
TIPSOTf (0.5)
To investigate the new function of the azaoligosacchar-
ides, we tried the possibility of a cyclic disaccharide. By
a Two mol equivalents of 17 might be synthesized from 15.

D. Sawada et al. / Tetrahedron Letters 46 (2005) 2399–2403
2401
sion of the two carbamate groups, was obtained as a sin-
gle stereoisomer in 10% yield. The measurement of
its 1H NMR at high temperature (100 °C, DMSO-d6 sol-
vent) resulted in broad peaks like a single sugar. Also in
this reaction, TMSOTf would activate the glycosyl bond
of 15 and the 1,6-anhydro azasugar 17 was also ob-
tained. To prevent the formation of 17, we tried the
reaction at lower temperature (À78 °C to À50 °C),
affording 16 in 60% yield (run 2). Using TBSOTf and
TIPSOTf as a bulky promoter decreased the yield in
16 (runs 3 and 4).
Using 18 and 19, the one-pot cyclization was also exam-
ined. The cyclic azadisaccharide 20 was obtained in 57%
(0.2M, run 6), and in 88% yield (0.3 M, run 7) from 18,
and similarly, 21 was obtained in 43% (0.2M, run 8),
and in 65% yield (0.3 M, run 9) from 19, which are given
as a single stereoisomer.
Then, we tried to synthesize another type of cyclic oligo-
saccharides. The known compound 22 was reacted with
NH3 in MeOH to afford the amide 23, whose diol moi-
ety was oxidatively cleaved by NaIO4. After stirring the
given mixture with 1 N HCl in THF, we could obtain
the azasugar derivative 24. The hydroxyl group of 24
was converted to TBS ether and the diastereomers were
separated. The amide nitrogen of 25 was protected by
Boc or methyl carbamate, and finally the reduction with
NaBH4 gave the precursors 28 and 29 for one-pot cycli-
zation reactions (Scheme 2). Using these compounds,
the cyclization under similar conditions used in Table
5 was carried out, and afforded the cyclic compounds
30 and 31 successfully. After several attempts, it gave
the best results when the compounds, whose C5 stereo-
chemistry was S (from 25b), were reacted in the reduced
substrate concentration (0.03 M) at low temperature
(À78 to À40 °C) (Scheme 3). The unfavoured isomer
25a with R stereochemistry at C5 was easily recycled:
cleavage of the TBS group by TBAF, and then stirring
with 1 N HCl in THF gave 24 with both C5 stereoiso-
mers. The cyclic compounds 30 and 31 indicated the
For the synthesis of the cyclic compounds, the 1,6-anhy-
dro azasugar 17 should be a good precursor (Table 5).
At first, TMSOTf was added to 17 in THF at À40 °C,
and then temperature of the mixture was raised to
0 °C; however, this reaction gave only trace amounts
of the cyclic compound. Fortunately, the addition of
TMSOH promoted the reaction, and the cyclic com-
pound 16 was obtained in 25% yield in 0.2 M and 31%
yield in 0.3 M. In this reaction, there is no other cyclic
compound composed of more than two azasugars. At
the reduced reaction temperature (À40 °C), we could
get the product in 77% yield, although the reaction pro-
ceeded a little slower, and 10% of 17 was recovered (run
4). To complete the reaction, TMSOTf was slowly
added for 15 min, but this trial was not satisfactory be-
cause of the decomposition of the product (run 5). Next,
for the synthesis of the azaoligosaccharide derivatives,
we modified the carbamate moiety. From the same inter-
mediate, which was converted to 6 and 17, the methyl
carbamate 18 and the Fmoc derivative 19 were synthe-
sized in three steps: (1) the amide protection of the aza-
sugar lactam by the methyl carbamate or Fmoc, (2)
reduction by NaBH4, (3) the removal of MPM by
DDQ and the spontaneous intramolecular cyclization.
1
symmetric H NMR.
OH
OH
OAc
O
b
a
BnO
BnO
BnO
BnO
NH2
BnO
BnO
O
O
23
22
TBSO
BnO
HO
H
N
NH
d or e
c
BnO
BnO
Table 5. One-pot synthesis of cyclic azadisaccharides
BnO
BnO
O
BnO
24
O
N
R
N
R
N
25a (R form at C5)
25b (S form at C5)
TMSOTf (0.5eq)
TMSOH (1 eq)
O
H
BnO
BnO
H
O
O
BnO
N
H
OBn
16 R = Boc
H
OBn
OBn
THF
BnO
BnO
R
N
R
f
R
BnO
BnO
BnO
BnO
TBSO OBnO
26 (R=Boc)
27 (R=CO2Me)
BnO
17 R = Boc
TBSO OBnOH
18 R = CO2Me
19 R = Fmoc
20 R = CO2Me
21 R = Fmoc
28 (R=Boc)
29 (R=CO2Me)
Run Substrate Concentration Temp.
of substrate
(M)
% Yield of
16/20/21a
(recovery of
S.M.)
Scheme 2. Reagents and conditions: (a) NH3, MeOH; 95%; (b) (1)
NaIO4, CH2Cl2, H2O, silica gel; (2) 1 N. HCl, THF; 95%; (c) TBSCl,
imidazole; 100% (25a:25b/4:3); (d) (Boc)2O, DMAP, CH3CN; 100%;
(e) ClCO2Me, n-BuLi, THF, À78 °C; 87%; (f) NaBH4, MeOH; 98% for
28, 82% for 29.
(°C)
1
2
3
4
5
6
7
8
9
17
17
17
17
17
18
18
19
19
0.2
0.2
0.3
0.3
0.3
0.20
0.3
0.20
0.3
À40 to 0
traceb
0
25 (20)
31 (17)
77 (10)
27 (20)c
0
À40
0
57 (17)
À78 to À40 88 (4)
R
N
R
N
H
H
TMSOTf
(0.5eq)
R
43 (15)
N
BnO
BnO
TBSO OBnOH
O
O
H
BnO
H
À20
65 (7)
OBn
OBn
BnO
BnO
THF
OBn
Fmoc: 9-fluorenylmethoxycarbonyl.
a % of weight per weight.
(0.03M)
28 (R=Boc)
30 (R=Boc, y. 43%)
31 (R=CO2Me, y. 57%)
-78ºC ~ -40ºC
29 (R=CO2Me)
b TMSOH was not added.
c TMSOTf was slowly added (15 min).
Scheme 3. One-pot synthesis of cyclic azadisaccharides.

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D. Sawada et al. / Tetrahedron Letters 46 (2005) 2399–2403
A. Helv. Chim. Acta 1991, 74, 2043; (d) Kajimoto, T.; Liu,
CO2Me
MeO2C
K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.;
Porco, J. A., Jr.; Wong, C.-H. J. Am. Chem. Soc. 1991,
113, 6187; (e) Dondoni, A.; Merino, P.; Perrone, D.
Tetrahedron 1993, 49, 2939; (f) Hudlicky, T.; Rouden, J.;
Luna, H.; Allen, S. J. Am. Chem. Soc. 1994, 116, 5099; (g)
Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv.
Chim. Acta 1995, 78, 514; (h) Takahata, H.; Banba, Y.;
Ouchi, H.; Nemoto, H. Org. Lett. 2003, 5, 2527; (i)
Sawada, D.; Takahashi, H.; Ikegami, S. Tetrahedron Lett.
2003, 44, 3085; (j) Takahata, H.; Banba, Y.; Ouchi, H.;
Nemoto, H.; Kato, A.; Adachi, I. J. Org. Chem. 2003, 68,
3603; (k) Heck, M.-P.; Vincent, S. P.; Murray, B. W.;
Bellamy, F.; Wong, C.-H.; Mioskowski, C. J. Am. Chem.
Soc. 2004, 126, 1971, and references cited therein.
N
H
N
H
O
H
H
H
H
H
H
O
H H
NOE
OH
OH
HO
HO
OH
OH
H
H
Figure 1. Proposed structure of 32.
3. (a) Winchester, B.; Fleet, G. W. J. Glycobiology 1992, 2,
199; (b) Legler, G. Adv. Carbohydr. Chem. Biochem. 1990,
48, 318; (c) Papandreou, G.; Tong, M. K.; Ganem, B. J.
Am. Chem. Soc. 1993, 115, 11682; (d) Sinnot, M. L. Chem.
Rev. 1990, 90, 1171; (e) Bols, M. Acc. Chem. Res. 1998, 31,
1; (f) Gijsen, H. J. M.; Qiao, L.; Fitz, W.; Wong, C.-H.
Chem. Rev. 1996, 96, 443; (g) Martin, O. R. In Carbohy-
drate Mimics; Concepts and Methods; Chapleur, Y., Ed.;
Wiley-VCH: Weinheim, 1998, p 259; (h) Depezay, J. C. In
Carbohydrate Mimics; Concepts and Methods; Chapleur,
Y., Ed.; Wiley-VCH: Weinheim, 1998, p 307.
Figure 2. The X-ray single-crystal structure of 33. Hydrogen atoms
were omitted.
As mentioned above, the glycosylation of azasugars
indicates high stereoselectivity. To confirm the stereo-
chemistry of the glycosyl bonds, 20 and 30 were further
transformed. The benzyl groups of 20 were removed by
Pd/C and H2 in THF to afford the hexa-hydroxyl com-
pound 32 in quantitative yield, whose 1H NMR was rela-
tively simple.15 Analyzing the NOE of 32, we speculate
its structure as shown in Figure 1.
4. (a) Knapp, S.; Choe, Y. H.; Reilly, E. Tetrahedron Lett.
1993, 34, 4443; (b) Suzuki, K.; Hashimoto, H. Tetrahedron
Lett. 1994, 35, 4119.
5. Aza-C-disaccharide, see: (a) Martin, O. R.; Liu, L.; Yang,
´
F. Tetrahedron Lett. 1996, 37, 1991; (b) Frerot, E.;
Marquis, C.; Vogel, P. Tetrahedron Lett. 1996, 37, 2023;
(c) Johns, B. A.; Pan, Y. T.; Elbein, A. D.; Johnson, C. R.
J. Am. Chem. Soc. 1997, 119, 4856.
6. Oligosaccharide analogues based on azasugars, see: Rut-
tens, B.; Van der Eycken, J. Tetrahedron Lett. 2002, 43,
2215.
7. Disaccharides containing an azasugar at the reducing end,
see: (a) Moss, S. F.; Southgate, R. J. Chem. Soc., Perkin
Trans. 1993, 1787; (b) Spohr, U.; Bach, M. Can. J. Chem.
1993, 71, 1943; (c) Takahashi, S.; Kuzuhara, H.; Naka-
jima, M. Tetrahedron 2001, 57, 6915.
8. Granier, T.; Vasella, A. Helv. Chim. Acta 1998, 81, 865.
9. Another example of a glycosidation using lanthanides, see:
Hosono, S.; Kim, W.-S.; Sasai, H.; Shibasaki, M. J. Org.
Chem. 1995, 60, 4.
Compound 30 was also debenzylated (100% yield), and
converted to hexa-4-bromobenzoyl compound 33 (60%
yield). The recrystallization of 33 was successful (from
ethyl acetate and MeOH) and its X-ray crystallographic
analysis indicates the structure of 33 as Figure 2. Thus,
the stereochemistry of the glycoside bonds in the cyclic
compounds was found to be all a-glycosides, and it is
disclosed that the glycosylation of these azasugars af-
fords an a-glycoside selectively.
10. (a) Pilli, R. A.; Dias, L. C.; Maldaner, A. O. J. Org. Chem.
1995, 60, 717; (b) Macdonald, S. J. F.; Clarke, G. D. E.;
Dowle, M. D.; Harrison, L. A.; Hodgson, S. T.; Inglis, G.
G. A.; Johnson, M. R.; Shah, P.; Upton, R. J.; Walls, S. B.
J. Org. Chem. 1999, 64, 5166; (c) Okitsu, O.; Suzuki, R.;
Kabayashi, S. Synlett 2000, 989; (d) Klitzke, C. F.; Pilli,
R. A. Tetrahedron Lett. 2001, 42, 5605; (e) Okitsu, O.;
Suzuki, R.; Kabayashi, S. J. Org. Chem. 2001, 66, 809; (f)
Sugiura, M.; Hagio, H.; Hirabayashi, R.; Kobayashi, S.
J. Am. Chem. Soc. 2001, 123, 12510.
In summary, we have developed glycosylation of azasu-
gars to obtain azaoligosaccharides. Also, the cyclic
azadisaccharides are successfully synthesized, and their
one-pot syntheses are demonstrated. These azaoligosac-
charides are thought to be precedents to develop various
oligosaccharides, novel biologically active compounds,
and new functional molecules. Study on their applica-
tion as functional molecules is now in progress in our
laboratory.
11. These compounds were prepared through the same steps
as for the synthesis of compound 1 using 6-(4-methoxy-
benzyl)-2,3,4-tri-O-benzyl-D-glucono-1,5-lactone. See also
Ref. 8.
References and notes
12. Suh, Y.-G.; Kim, S.-H.; Jung, J.-K.; Shin, D.-Y. Tetra-
hedron Lett. 2002, 43, 3165.
1. (a) Inouye, S.; Tsuruoka, T.; Ito, T.; Niida, T. Tetrahedron
1968, 23, 2124; (b) Ishida, N.; Kumagai, K.; Niida, T.;
Tsuruoka, T.; Yumato, H. J. Antibiot. 1967, 20, 66; (c)
Murao, S.; Miyata, S. Agric. Biol. Chem. 1980, 44, 219.
2. (a) Bashyal, B. P.; Chow, H.-F.; Fleet, G. W. J. Tetrahe-
dron Lett. 1986, 27, 3205; (b) Fleet, G. W. J.; Namgoong,
S. K.; Barker, C.; Baines, S.; Jacob, G. S.; Winchester, B.
Tetrahedron Lett. 1989, 30, 4429; (c) Ermert, P.; Vasella,
13. The 1H NMR is so complicated that it is difficult to know
the concise structure of this compound. However, it gives
a reasonable HR-Mass spectrum.
14. Because the azasugar itself might be a leaving group in
azaoligosaccharides, the cleavage of glycoside bond of 12
or 13 took place by TMSOTf, and same intermediate as
the reaction in Table 2 was generated in situ.

D. Sawada et al. / Tetrahedron Letters 46 (2005) 2399–2403
2403
21
1
15. Spectral data of 32: ½aꢀD +9.7 (c 1.15, MeOH); H NMR
3H), 3.76 (d, J = 5.5 Hz, 1H), 3.46 (m, 1H), 3.73 (m, 1H),
3.24 (dd, J = 5.7, 11.0 Hz, 1H), 3.24 (dd, J = 5.5, 11.0 Hz,
1H); 13C NMR (150 MHz, CD3OD) d 158.9, 157.4, 91.6,
91.0, 79.8, 79.7, 77.9, 77.5, 70.2, 68.2, 66.7, 66.6, 61.6, 61.0,
53.8, 53.5; FAB-MS m/z 461 (M+); FAB-HRMS calcd for
C16H26N2O12Na (M+) 461.1384, found 461.1381.
(600 MHz, CD3OD) d 5.33 (br s, 1H), 5.23 (br s, 1H), 4.25
(dd, J = 2.2, 12.4 Hz, 1H), 4.17 (dd, J = 2.5, 12.1 Hz, 1H),
4.05 (dd, J = 11.0, 11.0 Hz, 1H), 4.05 (dd, J = 11.0, 11.0 Hz,
1H), 3.95 (dd, J = 0.8, 12.4 Hz, 1H), 3.91 (dd, J = 1.2,
12.1 Hz, 1H), 3.76 (d, J = 5.7 Hz, 1H), 3.73 (s, 3H), 3.73 (s,