A facile access to aryl α-sialosides: The combination of a volatile amine base and acetonitrile in glycosidation of sialosyl chlorides

Article abstract of DOI:10.1055/s-1998-1717

We have succeeded in achieving a facile access to 4-nitrophenyl and 4-methylumbelliferyl-α-sialosides. To sialosyl chlorides which are fully protected with acetyl groups as glycosyl donors, the action of phenols with diisopropylethylamine in acetonitrile brought about high yield as well as facile product isolation.

Full text of DOI:10.1055/s-1998-1717

May 1998
SYNLETT
479
A Facile Access to Aryl α-Sialosides: the Combination of a Volatile Amine Base and
Acetonitrile in Glycosidation of Sialosyl Chlorides
Atsuhito Kuboki, Takahiro Sekiguchi, Takeshi Sugai,* Hiromichi Ohta
Department of Chemistry, Keio University, 3-14-1 Hiyoshi, Yokohama 223-8522, Japan
Fax 81 45 563 5967; sugai@chem.keio.ac.jp
Received 24 February 1998
Abstract: We have succeeded in achieving a facile access to 4-
nitrophenyl and 4-methylumbelliferyl-α-sialosides. To sialosyl
chlorides which are fully protected with acetyl groups as glycosyl
donors, the action of phenols with diisopropylethylamine in acetonitrile
brought about high yield as well as facile product isolation.
In recent years, the addition of sialic acids on the terminal of
oligosaccharides by means of the transglycosylation catalyzed by
1
2
sialidase
or trans-sialidase
has attracted attention, since
3
sialyloligosaccharides play important roles in many biological events
such as infection of the influenza virus, metastasis of cancer and so
4
5
Scheme 1
on. In these enzyme-catalyzed reactions, aryl α-sialosides have worked
2b,2d
very well as the substrates,
due to the irreversible process. Another
clinical importance of chromogenic 4-nitrophenyl (1) or fluorimetric 4-
methylumbelliferyl (2) α-sialosides has been emphasized in the
measurement of the activity and/or amount of expression of these
6
7-9
enzymes, based on a colorimetric or fluorimetric method.
The
methods for the preparation of such sialosides so far had mainly been
based on the nucleophilic displacement of glycosyl chlorides with
10
sodium phenoxides in N,N-dimethylformamide or equimolar use of
11
benzyltrimethylammonium phenoxides in a two-phase solvent system
12
besides other conventional glycosidations. Our recent success in the
13
preparative-scale synthesis of sialic acid and related compounds
prompted us to elaborate a more facile access to these α-sialosides.
of excessive amount of phenol (2 molar excess) to triethylamine (pKa
15
16
10.7 ) in acetonitrile as solvent. Encouraged by this result, we further
investigated the reaction conditions through changing the basicity and
steric bulkiness of the amine, expecting an increase of the yield of
15
glycoside 4b. Weaker bases such as pyridine (pKa 5.2 ) and N-
15
methylmorpholine (pKa 7.4 ) proved ineffective (Table 1, entry 3 and
4). On the other hand, the use of another base, diisopropylethylamine
17
(pKa 10.5 ) with an increased steric bulkiness, indeed, could suppress
the path via the direct abstraction of the proton on the 3-position to give
the undesired glycal and, accordingly, the ratio of glycoside to glycal
was dramatically enhanced (Table 1, entry 5).
Figure 1
14
In this attempt, Kasai's glycosidation procedure seemed attractive,
because evaporation of both the volatile amine base and solvent and the
subsequent chromatography would remarkably simplify the product
isolation in the workup procedure. Kasai and co-workers emphasized a
combination of phenols, triethylamine and glycosyl halides in
acetonitrile, which was successful in the case of the glycosidation of
2,3,4,6-tetra-O-acetyl-α-D-glucosaminyl chloride.
Scheme 2
At this point, efforts were focused on reducing the total amount of
reagents under a nearly fixed proportion of phenol to amine (1 : 0.9 to 1
: 0.8) in the glycosidation of 3a with 4-nitrophenol (Scheme 2). In a
practical sense, use of 10 molar excess of phenol was mostly effective
(Table 2, entry 8). Excessively decreasing the phenol markedly lowered
the reaction rate of glycosidation as well as the yield of glycoside.
In our first attempt for the glycosidation of a glycosyl chloride 3b with
2-nitrophenol under Kasai's glycosidation conditions, however, only the
elimination of the chlorine atom occurred, and glycal 5b was obtained
as the sole product (Scheme 1 and Table 1, entry 1). It turned out that
the yield of the desired product 4b, however, was improved with the use

480
LETTERS
SYNLETT
References and Notes
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18
Under thus optimized reaction conditions, 4-nitrophenyl and 4-
methylumberifellyl groups (Scheme 3) could be introduced to sialic acid
and KDN in good yield, respectively (Table 3).
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Related Substances; Gottschalk, A. Ed. Cambridge Univ. Press:
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Ann./Recuiel 1997, 1059-1064.
The use of benzyl ester in place of more commonly used methyl ester 3c
deserves comment. Any contamination of glycal (5a-c) in α-sialoside
(6/7a-c) should be thoroughly avoided, since the eventually deprotected
19
(4) Suzuki, T.; Tsukimoto, M.; Kobayashi, M.; Yamada, A.;
Kawaoka, Y.; Webster, T. G.; Suzuki, Y. J. Gen. Virol. 1994, 75,
1769-1774. Suzuki, Y. Prog. Lipid Res. 1994, 33, 429-457.
form of glycal works as the inhibitor for sialidase. Although
glycosides could be obtained in better yield from methyl ester donor 3c
(98%, Table 3, entry 12) than benzyl ester donor 3a (94%, Table 3,
entry 13), the separation of glycoside 6c from glycal 5c was very
laborious due to an almost identical chromatographic behavior of these
products. In the case of benzyl ester donor 3a, in contrast, glycal 5a
could be easily removed because of the highly crystalline nature of the
glycoside 6a.
(5) Kurosaka, A.; Nakajima, H.; Funakoshi, I.; Matsuyama, M.;
Nagayo, T.; Yamashina, I. J. Biol. Chem. 1983, 258, 11594-
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Matsumoto, M.; Ueda, S.; Kato, S. Cancer Res. 1985, 45, 3796-
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Kameyama, M.; Imaoka, S.; Furukawa, H.; Ishikawa, O.; Sasaki,
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Res. 1993, 53, 3623-3627.
Scheme 3
(6) Shenkman, S.; Jiang, M.-S.; Hart, G. W.; Nussenzweig, V. A. Cell
1991, 65, 1117-1125. Vandekerckhove, F.; Schenkman, S.; Pontes
de Carvalho, L.; Tomlinsin, S.; Kiso, M.; Yoshida, M.; Hasegawa,
A.; Nussenzweig, V. Glycobiology 1992, 2, 541-548. Guo, X.;
Laver, W. G.; Vimr, E.; Sinnott, M. L. J. Am. Chem. Soc. 1994,
116, 5572-5578. Lee, K. B.; Lee, Y. C. Anal. Biochem. 1994, 216,
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Y.; Troy, F. A.; Kitajima, K. J. Biol. Chem. 1996, 271, 2909-
2913.
In conclusion, we have achieved a facile access to aryl α-sialosides.
Combination of phenols and volatile diisopropylethylamine in
20
acetonitrile brought about the high yield as well as the facile product
isolation, whose results can be applied to scaled-up preparation.
The authors thank Nippon Gaishi Co. for the generous gift of N-
acetylneuraminic acid. We are grateful to Prof. Kazuo Achiwa,
University of Shizuoka, Dr. Toshio Nishikawa, Nagoya University and
Prof. Yoshitaka Ichikawa, Johns Hopkins University, for valuable
discussions. This work was supported by the Special Coordination
Funds of the Science and Technology Agency of the Japanese
Government and Kato Bioscience Foundation, which are acknowledged
with thanks.
(7) Nagai, T.; Miyauchi, Y.; Tomimori, T.; Suzuki, Y.; Yamada, H.
Chem. Pharm. Bull. 1990, 38, 1329-1332. Sinnott, M. L.; Guo, X.;
Li, S.-C.; Li, Y.-T. J. Am. Chem. Soc. 1993, 115, 3334-3335.
Nagai, T.; Suzuki, Y.; Yamada, H. Biol. Pharm. Bull. 1995, 18,
1251-1254. Yuziuk, J. A.; Nakagawa, H.; Hasegawa, A.; Kiso,
M.; Li, S.-C.; Li, Y.-T. Biochem. J. 1996, 315, 1041-1048.
(8) Potier, M.; Mameli, L.; Belisle, M.; Dallaire, L.; Melancon, S. B.
Anal. Biochem. 1979, 94, 287-296. Chang, A. K. J.; Pegg, M. S.;
von Itzstein, M. Biochem. Int. 1991, 24, 165-171. Chong, A. K. J.;

May 1998
SYNLETT
481
Pegg, M. S.; Taylor, N. R.; von Itzstein, M. Eur. J. Biochem.
1H, J = 4.4, 12.5 Hz), 2.76 (dd, 1H, J = 4.6, 12.7 Hz), 2.38 (d, 1H,
1992, 207, 335-343. Angata, T.; Kitajima, K.; Inoue, S.; Chang,
J.; Warner, T. G.; Troy, F. A. I.; Inoue, Y. Glycobiology 1994, 4,
517-523. Wilson, J. C.; Angus, D. I.; von Itzstein, M. J. Am.
Chem. Soc. 1995, 117, 4214-4217.
J = 1.0 Hz), 2.29 (dd, 1H, J = 12.7, 12.7 Hz), 2.18-1.92 (s, 3Hx5);
13
C NMR (100 MHz, CDCl ) δ 170.80, 170.62, 170.24, 170.18,
3
170.01, 167.47, 160.89, 156.72, 154.14, 152.24, 133.96, 128.70,
128.39, 128.29, 125.64, 115.91, 114.94, 113.25, 107.13, 99.82,
73.86, 69.03, 68.30, 68.11, 67.17, 61.98, 49.26, 38.61, 23.20,
(9) Meindl, P.; Tuppy, H. Monatsh. Chem. 1967, 98, 53-60. Tuppy,
H.; Palese, P. FEBS Lett. 1969, 3, 2785-2792. Santer, U. V.; Yee-
Foon, J.; Glick, M. C. Biochem. Biophys. Acta 1978, 523, 435-
442. Cabezas, J. A.; Calvo, P.; Eid, P.; Martin, L.; Perez, N.;
Regelero, A.; Hannoun, C. Biochem. Biophys. Acta 1980, 616,
228-238. Fujii, I.; Iwabuchi, Y.; Teshima, T.; Shiba, T.; Kikuchi,
M. BioMed. Chem. 1993, 1, 147-150.
+
21.00, 20.81, 20.73, 18.70; MS (70 eV) m/z (%) 725 (M , 3), 664
(7), 549 (14), 490 (base peak), 448 (9), 414 (22), 370 (11), 328
(13), 268 (11), 245 (4), 218 (6), 176 (42), 148 (30), 119 (6);
+
HRMS m/z Found 668.1980 (M +1-Ac-CH ). C
H N O
33 34 1 14
3
requires 668.6313.
Benzyl (4-nitrophenyl 4,7,8,9-tetra-O-acetyl-5-acetylamino-3,5-
dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate (6a).
(10) (a) Warner, T. G.; O'Brien, J. S. Biochemistry 1979, 18, 2783-
2787. (b) Myers, R. W.; Lee, R. T.; Lee, Y. C.; Thomas, G. H.;
Reymonds, L. W.; Uchida, Y. Anal. Biochem. 1980, 101, 166-
174. (c) Eschenfelder, V.; Brossmer, R. Carbohydr. Res. 1987,
162, 294-297. (d) Furuhata, K.; Ogura, H. Chem. Pharm. Bull.
1989, 37, 2037-2040. (e) Furuhata, K.; Komiyama, K.; Ogura, H.;
Hata, T. Chem. Pharm. Bull. 1991, 39, 255-259.
10d
11b
Mp 82.0-82.5 °C [lit.
mp 88-90 °C, lit.
mp 66-70 °C];
24
24
[α]
[lit.
–4.9 (c, 0.98, chloroform), [α]
+20 (c, 1, methanol), lit.
methanol)]; H NMR (400 MHz, CDCl ) δ 7.98 (m, 2H,
–0.6 (c, 0.98, methanol)
D
D
10c
22
11b
20
[α]
[α]
+5.5 (c, 1.01,
D
D
1
3
aromatic), 7.25-7.15 (m, 5H, aromatic), 7.00 (m, 2H, aromatic),
5.35 (d, 1H, J = 1.2 Hz), 5.35 (ddd, 1H, J = 1.2, 2.2, 5.0 Hz), 5.22
(d, 1H, J = 10.3 Hz), 5.19 (d, 1H, J = 11.7 Hz), 4.97 (ddd, 1H, J =
4.6, 10.5, 13.2 Hz), 4.93 (d, 1H, J = 11.7 Hz), 4.68 (d, 1H, J = 10.8
Hz), 4.22 (dd, 1H, J = 2.2, 12.6 Hz), 4.14 (ddd, 1H, 10.3, 10.5,
10.8 Hz), 4.09 (dd, 1H, J = 5.0, 12.6 Hz), 2.77 (dd, 1H, J = 4.6,
(11) (a) Rothermel, J.; Faillard, H. Carbohydr. Res. 1990, 196, 29-40.
(b) Reinhard, B.; Faillard, H. Liebigs Ann. Chem. 1994, 193-203.
(12) Privalova, J. M.; Khorlin, Y. A. Izv. Akad. Nauk SSSR, Ser. Khim.
1969, 2785-2792. Vzdykhan'ko, A. S.; Glushenko, V. V.;
Mirzayanova, M. N.; Khorlin, A. Y. Izu. Akad. Nauk SSSR, Ser.
Khim. 1976, 699-701. Baggett, N.; Marsden, B. J. Carbohydr.
Res. 1982, 110, 11-18. Schreiner, E.; Zbiral, E. A. Liebigs Ann.
Chem. 1990, 581-586.
13.2 Hz), 2.31 (dd, 1H, J = 12.3, 13.2 Hz), 2.20-1.93 (s, 3Hx5);
13
C NMR (100 MHz, CDCl ) δ 170.80, 170.57, 170.23, 170.04,
3
169.97, 167.61, 158.95, 143.23, 133.74, 128.78, 128.73, 128.43,
125.48, 118.24, 99.48, 73.79, 68.33, 68.29, 68.15, 66.91, 62.07,
49.22, 38.85, 23.20, 20.99, 20.80, 20.73 (Cx2); MS (70 eV) m/z
(%) 552 (23), 490 (64), 415 (4), 370 (8), 310 (7), 268 (4), 218 (4),
139 (13), 91 (base peak); Its NMR spectrum was in good
(13) Sugai, T.; Kuboki, A.; Hiramatsu, S.; Okazaki, H.; Ohta, H. Bull.
Chem. Soc., Jpn. 1995, 68, 3581-3589. Kuboki, A.; Okazaki, H.;
Sugai, T.; Ohta, H. Tetrahedron 1997, 53, 2387-2400.
11b
accordance with that reported previously.
23
According to the reported procedure, benzyl ester and O-acetyl
(14) Kasai, K.; Okada, K.; Yamaji, N. Chem. Pharm. Bull. 1995, 43,
group of protected 4-methylumbelliferyl and 4-nitrophenyl α-
sialosides were hydrolyzed in basic conditions to give
corresponding α-sialosides in 99% and 97 % yield, respectively.
Sodium (4-nitrophenyl 5-acetylamino-3,5-dideoxy-D-glycero-α-
266-270.
(15) Hall, J. H. K. J. Phys. Chem. 1956, 60, 63-70.
(16) 1,2-Dichloroethane and dichloromethane as a solvent made the
reaction very slow. Moreover, in the case of tetrahydrofuran and
1,4-dioxane as a solvent, the reaction hardly proceeded.
1
D-galacto-2-nonulopyranosid)onate (1a). H NMR (400 MHz,
D O) δ 8.20 (d, 2H, J = 9.3 Hz), 7.22 (d, 2H, J = 9.3 Hz), 4.14 (dd,
2
1H, J = 1.2, 10.5 Hz), 3.94 (dd, 1H, J = 9.8, 10.5 Hz), 3.82 (dd,
1H, J = 2.2, 12.5 Hz), 3.81 (ddd, 1H, J = 2.2, 6.8, 9.8 Hz), 3.76
(ddd, 1H, J = 4.6, 9.8, 10.0 Hz), 3.60 (dd, 1H, J = 6.8, 12.5 Hz),
3.57 (dd, 1H, J = 1.2, 9.8 Hz), 2.82 (dd, 1H, J = 4.6, 12.6 Hz), 2.02
(s, 3H), 2.00 (dd, 1H, J = 10.0, 12.6 Hz). Its NMR spectrum was in
(17) Kricheldorf, H. R. Makromol. Chem. 1974, 175, 3325-3342.
(18) Typical glycosidation procedure: benzyl (4,7,8,9-tetra-O-acetyl-5-
acetylamino-2-chloro-2,3,5-trideoxy-D-glycero-α-D-galacto-2-
21
nonulopyranosid)onate (3a, 100 mg, 0.17 mmol) was added to a
solution of 4-methylumbelliferone (4-methyl-2-oxo-2H-1-
benzopyran-7-ol) (302 mg, 1.71 mmol) and diisopropyl-
ethylamine (245 µl, 1.41 mmol) in acetonitrile (4 ml) at room
temperature for 3 h. A reaction mixture was concentrated in vacuo
and diluted with toluene for three times. The resultant residue was
charged on a column of silica gel (33 g) and eluted with ethyl
acetate-n-hexane (4 : 1) to give 7a (106 mg, 85 %) and 5c (5 mg, 5
%). 4-Nitrophenol and 4-methylumbelliferone could easily be
recovered after chromatographic separation, and were reused
without any further purification.
11a
good accordance with that reported previously.
Sodium (4-methyl-2-oxo-2H-1-benzopyran-7-yl 5-acetylamino-
3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate
1
(2a). H NMR (400 MHz, D O) δ 7.66 (m, 1H, aromatic), 7.15
2
(m, 2H, aromatic), 6.22 (d, 1H, J = 1.0 Hz), 4.05 (dd, 1H, J = 1.5,
10.5 Hz), 3.93 (dd, 1H, J = 9.8, 10.5 Hz), 3.86 (ddd, 1H, J = 2.4,
6.4, 9.0 Hz), 3.85 (dd, 1H, J = 2.4, 12.0 Hz), 3.77 (ddd, 1H, J =
4.6, 9.8, 11.7 Hz), 3.61 (dd, 1H, J = 6.4, 12.0 Hz), 3.58 (dd, 1H, J
= 1.5, 9.0 Hz), 2.85 (dd, 1H, J = 4.6, 12.7 Hz), 2.40 (d, 1H, J = 1.0
Hz), 2.02 (s, 3H), 1.97 (dd, 1H, J = 11.7, 12.7 Hz). Its NMR
spectrum was in good accordance with that reported
Benzyl (4-methyl-2-oxo-2H-1-benzopyran-7-yl 4,7,8,9-tetra-O-
acetyl-5-acetylamino-3,5-dideoxy-D-glycero-α-D-galacto-2-
11a
previously.
26
nonulopyranosid)onate (7a). [α]
+28.6 (c, 1.01, chloroform).
D
1
H NMR (400 MHz, CDCl ) δ 7.32 (d, 1H, J = 8.8 Hz), 7.21-7.02
(19) Meindl, P.; Tuppy, H. Monatsh. Chem. 1969, 100, 1295-1306.
Palese, P.; Schulman, J. H. Chemoprophylaxis and virus infection
of the upper respiratory tract Vol. 1, Oxford, J. S. Ed. CRC:
Cleaveland, 1977, pp 189-205. Miller, C. A.; Wang, P.; Flashner,
M. Biochem. Biophys. Res. Commun. 1978, 83, 1479-1487.
Schreiner, E.; Zbiral, E.; Kleineidam, R. G.; Schauer, R. Liebigs
Ann. Chem. 1991, 129-134. von Itzstein, M.; Wu, W.-Y.; Kok, G.
3
(m, 5H, aromatic), 6.95 (dd, 1H, J = 2.4, 8.8 Hz), 6.84 (d, 1H, J =
2.4 Hz), 6.19 (d, 1H, J = 1.0 Hz), 5.38 (dd, 1H, J = 1.7, 8.3 Hz),
5.36 (ddd, 1H, J = 2.7, 4.4, 8.3 Hz), 5.26 (d, 1H, J = 10.3 Hz), 5.18
(d, 1H, J = 11.7 Hz), 4.95 (ddd, 1H, J = 4.6, 10.3, 12.7 Hz), 4.94
(d, 1H, J = 11.7 Hz), 4.61 (dd, 1H, J = 1.7, 10.8 Hz), 4.27 (dd, 1H,
J = 2.7, 12.5 Hz), 4.15 (ddd, 1H, J = 10.3, 10.3, 10.8 Hz), 4.12 (dd,

482
LETTERS
SYNLETT
25
B.; Pegg, M. S.; Dyason, J. C.; Jin, B.; van Phan, T.; Smuthe, M.
L.; White, H. F.; Oliver, S. W.; Colman, P. M.; Varghese, J. N.;
Ryan, D. M.; Woods, J. M.; Bethell, R. C.; Hotham, V. J.;
Cameron, J. M.; Penn, C. R. Nature 1993, 363, 418-423.
[α]
–37.3 (c, 1.10 chloroform)] in acetic acid (4 mL) was
D
added acetyl chloride (0.4 mL) and dry HCl gas was bubbled (15-
20 min) at 4 °C. The reaction flask was stoppered, and the mixture
was stirred at room temperature for 3 h. In most cases, the
disappearance of the starting material was confirmed within 3 h by
TLC analysis. If the starting material was still observed at this
stage, HCl gas was further bubbled for 2-3 min and the reaction
was further continued. The workup procedure was as followed.
The mixture was concentrated in vacuo. The residue was
concentrated with toluene for several times to remove acetic acid.
The residue was chromatographed on silica gel and the desired
fractions were concentrated in vacuo. The glycosyl chloride was
obtained as a solid (89 mg, 93 %). This was employed in the next
step without further purification. The glycosyl chloride related to
KDN could be prepared in same manner. Although, starting from
an anomeric mixture of peracetates, the substitution with chloride
proceeds, the authors recommends the use of pure β-anomer of
peracetate as the starting material. As the reaction of α-anomer is
slow, the prolonged reaction until the complete disappearance of
the both anomers of starting peracetates brought about the further
substitution at 9-position as well as the decomposition
(substitution with hydroxy group at 2-position) of desired product.
(20) 4-Nitrophenol could be introduced in an exclusive β-orientation in
the reaction with tri-O-acetyl-α-N-acetylglucosaminyl chloride
(quantitative) and tetra-O-acetyl-α-galactosyl bromide (93%),
respectively. On the other hand, the low reactivity of this system
was revealed on the glycosidation of α-mannosyl and 2-O-acyl β-
cf.24
glucosyl halides.
4-Nitrophenyl
2-acetylamino-3,4,6-tri-O-acetyl-2-deoxy-β-D-
25
glucopyranoside. Mp 248.0-249.0 °C [lit. mp 237.4-238.4 °C];
25
25
[α]
1
–25.6 (c, 0.5, chloroform). [lit. [α] –9.6 (chloroform)];
D
D
H NMR (400 MHz, CDCl ) δ 8.19 (2H, aromatic), 7.07 (2H,
3
aromatic), 5.62 (d, 1H, J = 8.6 Hz), 5.46 (d, 1H, J = 8.1 Hz), 5.45
(dd, 1H, J = 9.5, 10.5 Hz), 5.14 (dd, 1H, J = 9.5, 9.8 Hz), 4.28 (dd,
1H, J = 5.6, 12.5 Hz), 4.17 (dd, 1H, J = 2.4, 12.5 Hz), 4.11 (ddd,
1H, J = 8.1, 8.6, 10.5 Hz), 3.94 (ddd, 1H, J = 2.4, 5.6, 9.8 Hz),
2.07 (s, 3Hx2), 2.06 (s, 3H), 1.96 (s, 3H). Its NMR spectrum was
25
in good accordance with that reported previously. Anal. Calc.
for C
H N O : C, 51.28; H, 5.16; N, 5.98. Found C, 51.43; H,
20 24 2 11
5.20; N, 6.02.
4-Nitrophenyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside. Mp
(22) Nakamura, M.; Furuhata, K.; Ogura, H. Chem. Pharm. Bull. 1989,
37, 821-823.
26
25
146.0-147.0 °C [lit. mp 143-145 °C]; [α]
–10.0 (c, 2.0,
D
26
22
1
chloroform). [lit. [α]
–10 (c, 2 chloroform)]; H NMR (400
D
(23) Furuhata, K.; Komiyama, K.; Ogura, H.; Hata, T. Chem. Pharm.
Bull. 1991, 39, 255-259.
MHz, CDCl ) δ 8.21 (2H, aromatic), 7.07 (2H, aromatic), 5.52 (d,
3
1H, J = 7.7, 10.3 Hz), 5.48 (m, 1H), 5.17 (d, 1H, J = 7.7 Hz), 5.14
(dd, 1H, J = 3.7, 10.3 Hz), 4.23 (dd, 1H, J = 7.0, 11.3 Hz), 4.16
(dd, 1H, J = 5.8, 11.3 Hz), 4.13 (m, 1H), 2.19 (s, 3H), 2.07 (s,
3Hx2), 2.02 (s, 3H). Its NMR spectrum was in good accordance
(24) Roy, R.; Tropper, F. D.; Cao, S.; Kim, J. M. ACS Symp. Ser. 1997,
659, 163-180.
(25) Roy, R.; Tropper, F. D. Can. J. Chem. 1991, 69, 817-821.
26
with that reported previously.
(26) Dess, D.; Keleine, P.; Weinberg, D.V.; Kaufman, R.J.; Sidhu, R.S.
(21) The glycosyl chloride 3a was prepared starting from the
Synthesis 1981, 883-884.
27
corresponding peracetate in an essentially same manner reported
22
27
by Ogura and Furuhata.
To
a
solution of peracetate
(27) Shimizu, C.; Ikeda, K.; Achiwa, K. Chem. Pharm. Bull. 1988, 36,
20
[crystalline β-form 100 mg, 0.164 mmol, mp 123.5-124.0 °C,
1772-1778. Mp 113-115 °C, [α]
–29.1 (c, 1.0 chloroform).
D