T. Kajimoto et al. / Bioorg. Med. Chem. Lett. 16 (2006) 5736–5739
5739
10.1 Hz, 1H, H-5), 3.93 (t, J = 6.6 Hz, 2H, PhOCH2), 4.19
(dd, A part of AB type, J = 2.4 and 12.3 Hz, 1H, H-6),
4.27 (dd, B part of AB type, J = 4.6 and 12.3 Hz, 1H, H-
6), 4.28 (t, J = 10.1 Hz, H-4, 1H), 5.09 (t, J = 9.6 Hz, 1H,
H-3), 5.57 (d, J = 10.5 Hz, 1H, H-1), 5.75 (dd, J = 10.5
and 9.6 Hz, H-2), 6.78 and 7.33 (each d, AB type,
J = 8.8 Hz, 1H), 7.75 and 7.88 (each dd, AB type,
J = 3.0 and 5.3 Hz, 1H).
rides. It is noteworthy that there were almost no differenc-
es in terms of chemical yield and anomeric selectivities be-
tween the reactions using thioglycosides prepared with 2
and those prepared with 1. Thus, newly synthesized odor-
less thiol 2 was convenient to use for the purpose of fine
chemistry while the previously prepared thiol was useful
for industrial and large-scale synthesis. Our method
would be widely acceptable as a general method in many
syntheses of biologically active oligosaccharides subject-
ed in both solid and homogeneous phases.
9. General method for the synthesis of thioglycosides:
boron trifluoride diethyl etherate (0.6 ml) was added to
a solution of odorless benzenethiol (1 or 2, 4.5 mmol)
and peracetylated monosaccharide (4.0 mmol) in dichlo-
romethane (20 ml) at 0 °C, and the mixture was stirred
for 12 h at room temperature. The reaction mixture was
poured into ice-water and extracted with ethyl acetate.
The organic layer was washed with brine, dried over
MgSO4, and condensed in vacuo. The residue was
purified by silica gel chromatography to afford the
desired thioglycoside.
Acknowledgments
This research was financially supported in part by Fron-
tier Research Program and the 21st Century Center of
Excellence Program ‘‘Development of Drug Discovery
Frontier Integrated from Tradition to Proteome’’ of
the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
´
10. Liptak, A.; Imre, J.; Harangi, J.; Nanasi, P.; Nezmelyi, A.
Tetrahedron 1982, 38, 3721; and also see Watanabe, S.;
Sueyoshi, T.; Ichikawa, M.; Uehara, C.; Iwamura, M.
Org. Lett. 2001, 3, 255.
11. 1H NMR (300 MHz, CDCl3) of 13; d: 0.89 (br t,
J = 7.0 Hz, 3H), 1.2–1.6 (m, 12H), 2.14 (s, 3H), 3.85 (t,
J = 9.9 Hz, 1H), 3.93 (t, J = 6.6 Hz, 2H, PhOCH2), 4.01
(dd, J = 3.5 and 9.9 Hz, 1H), 4.12 (t, J = 9.9 Hz, 1H), 4.23
(dd, J = 4.8 and 10.3 Hz, 1H), 4.38 (dt, J = 4.8 and 9.9 Hz,
1H), 4.68 and 4.73 (each d, AB type, J = 12.2 Hz, 1H),
5.28 (d, J = 1.5 Hz, 1H, H-1), 5.60 (dd, J = 1.5 and 3.5 Hz,
1H, H-2), 5.64 (s, 1H, PhCH<), 6.81 (d, J = 8.8 Hz, 2H),
7.2–7.4 (m, 10H), 7.52 (d, J = 8.8 Hz, 2H).
References and notes
1. For example (a) Nicolaou, K. C. J. Am. Chem. Soc. 1997,
119, 449; (b) Hanashima, S.; Manabe, S.; Inamori, K.;
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5674.
2. (a) Node, M.; Kumar, K.; Nishide, K.; Ohsugi, S.;
Miyamoto, T. Tetrahedron Lett. 2001, 42, 9207; (b)
Nishide, K.; Miyamoto, T.; Kumar, K.; Ohsugi, S.; Node,
M. Tetrahedron Lett. 2002, 43, 8569; (c) Nishide, K.;
Ohsugi, S.; Fudesaka, M.; Kodama, S.; Node, M. Tetra-
hedron Lett. 2002, 43, 5177; (d) Ohsugi, S.; Nishide, K.;
Oono, K.; Okuyama, K.; Fudesaka, M.; Kodama, S.;
Node, M. Tetrahedron 2003, 59, 8393; (e) Node, M. Foods
& Food Ingredients J. Jpn. 2004, 209, 88; (f) Nishide, K.;
Patra, P. K.; Matoba, M.; Shanmugasundaram, K.; Node,
M. Green Chem. 2004, 6, 142; (g) Nishide, K.; Ohsugi, S.;
Miyamoto, T.; Kumar, K.; Node, M. Monatsh. Chem.
2004, 135, 189; (h) Nishide, K.; Node, M. J. Synth. Org.
Chem. Jpn. 2004, 62, 895; (i) Patra, P. K.; Nishide, K.;
Fuji, K.; Node, M. Synthesis 2004, 1003.
3. Hasegawa, J.; Hamada, M.; Miyamoto, T.; Nishide, K.;
Kajimoto, T.; Uenishi, J.; Node, M. Carbohydr. Res. 2005,
340, 2360.
4. Dohi, H.; Nishida, Y.; Tanaka, H.; Kobayashi, K. Synlett
2001, 1446; Nishida, Y.; Tsurumi, T.; Sasaki, K.; Watan-
abe, K.; Dohi, H.; Kobayashi, K. Org. Lett. 2003, 5, 3775.
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12. Konradsson, P.; Udodong, U.; Fraser-Reid, B. Tetrahe-
dron Lett. 1990, 31, 4313.
13. 1H NMR of 29 (300 MHz, CDCl3); d: 0.1 (s, 9H), 1.0 (m,
2H), 2.16 (s, 3H), 3.4–4.1 (m, 13H), 4.20 (br d, J = 6.0 Hz,
1H), 4.37 (d, J = 7.9 Hz, 1H), 4.50 (d, J = 11.0 Hz, 1H),
4.63 (d, J = 11.9 Hz, A part of AB, 1H), 4.70 (d,
J = 11.9 Hz, B part of AB, 1H), 4.74 (dd, J = 4.0 and
11.0 Hz, 1H), 4.81 (d, J = 10.0 Hz, 1H), 4.86 (d,
J = 1.5 Hz, 1H, man-1), 4.96 (dd, J = 4.3 and 11.0 Hz,
2H), 5.46 (dd, J = 1.5 and 4.0 Hz, 1H, man-2), 5.61 (s, 1H,
PhCH<), 7.1–7.4 (m, 23H), 7.46 (m, 2H).
14. General method for glycosylation: silver triflate (32 mg)
and NIS (70 mg) were successively added to a suspen-
sion of thioglycoside (0.125 mmol), acceptor glycoside
(0.125 mmol), and molecular sieves 4A (200 mg) in
dichloromethane (5 ml), and the mixture was stirred at
room temperature. After the reaction, the reaction
mixture was filtrated through CeliteÒ, and the filtrate
was partitioned between ethyl acetate and water. The
organic layer was washed with saturated aqueous
solution of sodium thiosulfate, dried over MgSO4, and
condensed in vacuo. The residue was purified by silica
gel chromatography.
6. Khan, S. H.; Crawley, S. C.; Kanie, O.; Hindsgaul, O.
J. Biol. Chem. 1993, 268, 2468.
7. Preparation of 2: sulfuric acid (5.0 ml) was added to octyl
phenyl ether (5.0 g), and the mixture was stirred for 30 min
at room temperature. The mixture was poured into a
saturated aqueous solution of sodium chloride, and
appearing precipitates were collected by suction. After
drying the precipitates by freeze-dry, a part of the
obtained sodium sulfonate (2.0 g) was treated with
refluxed thionyl chloride (7.5 ml) for 8–10 h to convert
to sulfonyl chloride, which was reduced with LiAlH4
(600 mg) in refluxed tetrahydrofuran (45 ml) for 10 h. The
reaction residue obtained by usual work-up was purified
by silica gel column chromatography (hexane/ethyl ace-
tate = 100:1) afforded 2.
15. 1H NMR of 33 (300 MHz, CDCl3); d: À0.01 (s, 9H), 1.05
(m, 2H), 1.83 (s, 3H, NHAc), 2.01, 2.02, and 2.03 (each s,
3H, OAc), 3.76 and 3.44 (each t, J = 9.0 Hz, 2H), 3.55–
3.95 (m, 12H), 4.05–4.25 (m, 5H), 4.27 (dd, J = 5.0 and
12.1 Hz, 1H), 4.40 (d, J = 10.4 Hz, 1H), 4.42 (d,
J = 13.4 Hz, 1H), 4.73 (s, 2H), 4.75–4.80 (m, 2H), 4.84
(d, J = 1.7 Hz, 1H), 4.90–5.05 (m, 2H), 5.04 (d,
J = 19.8 Hz, 1H), 5.52 (dd, J = 1.7 and 3.0 Hz, 1H, man-
2), 5.53 (d, J = 19.8 Hz, 1H), 5.59 (s, 1H, PhCH<), 7.1–7.4
(m, 23H), 7.43 (m, 2H).
16. Hasegawa, A.; Nagahama, T.; Ohki, H.; Hotta, K.;
Ishida, H.; Kiso, M. J. Carbohydr. Res. 1991, 10, 493;
Veeneman, G. H.; van Leeumen, S. H.; van Boom, J. H.
Tetrahedron Lett. 1990, 31, 1331.
8. 1H NMR (300 MHz, CDCl3); d: 0.89 (br t, J = 7.0 Hz,
3H), 1.2–1.6 (m, 12H), 1.78 (quint, J = 7.0 Hz, 2H), 1.83,
2.01, and 2.10 (each s, 3H), 3.84 (ddd, J = 2.4, 4.6, and