2976
T. Yamanoi et al.
LETTER
R1
O
(5) (a) Kraus, G. A.; Molina, M. T. J. Org. Chem. 1988, 53,
752. (b) Czernecki, S.; Ville, G. J. Org. Chem. 1989, 54,
610.
(6) (a) Schlesselmann, P.; Fritz, H.; Lehmann, J.; Uchiyama, T.;
Brewer, C. F.; Hehre, E. J. Biochemistry 1982, 21, 6606.
(b) Brockhaus, M.; Lehmann, J. Carbohydr. Res. 1977, 53,
21. (c) Li, X.; Ohtake, H.; Takahashi, H.; Ikegami, S. Synlett
2001, 1885. (d) Penner, M.; Taylor, D.; Desautels, D.;
Marat, K.; Schweizer, F. Synlett 2005, 212.
(7) (a) Li, X.; Ohtake, H.; Takahashi, H.; Ikegami, S.
Tetrahedron 2001, 57, 4297. (b) As the analogues of the 1-
C-alkyl-hexopyranose derivatives, the glycosidation using
the 1-C-alkoxyalkyl-hexopyranose derivatives was reported.
See: Heskamp, B. M.; Veeneman, G. H.; van der Marel, G.
A.; van Boeckel, C. A. A.; van Boom, J. H. Tetrahedron
1995, 51, 5657. (c) As the 1-C-alkyl-hexofuranose
derivative, the glycosidation using 2,3:5,6-di-O-isopropyl-
idene-1-C-methyl-D-mannofuranosyl acetate was reported.
See: Dondoni, A.; Marra, A.; Rojo, I.; Scherrmann, M.-C.
Tetrahedron 1996, 52, 3057.
AcO
BnO
BnO
R2 OH
9, 12
R1
O
AcO
BnO
R3
BnO
R2
OH
11a–e
R1
O
AcO
BnO
BnO
O
+
R2
R1
O
HO
10, 13
BnO
BnO
R3
R2
OH
1a–e, 6a
9, 10, 11a–e, 1a–e: R1 = H, R2 = –OBn
12, 13, 6a: R1 = –OBn, R2 = H
R
3 = a: Me; b: –CH2CH=CH2; c: n-Bu; d: Ph; e: Bn
(8) Yamanoi, T.; Oda, Y.; Yamazaki, I.; Shinbara, M.;
Morimoto, K.; Matsuda, S. Lett. Org. Chem. 2005, 2, 242.
(9) Compounds 1a–e and 6a were synthesized as follows
(Scheme 3). The reaction of 6-O-acetyl-2,3,4-tri-O-benzyl-
D-glucopyranose (9) using DMSO–Ac2O gave the
Scheme 3
(12) Typical Intramolecular Glycosidation Procedure (Table
1, Entry 4).
corresponding 6-O-acetyl-2,3,4-tri-O-benzyl-D-glucono-
1,5-lactone (10) in the good yield of 92%. The alkyl groups
were then introduced into C-1 of 10 by the reaction of the
carbonyl group at C-1 with organometallic reagents such as
RMgX or RLi. The reaction of 10 with MeLi (2.4 equiv) in
dry THF at –78 °C gave 6-O-acetyl-2,3,4-tri-O-benzyl-1-C-
methyl-a-D-glucopyranose (11a) and 2,3,4-tri-O-benzyl-1-
C-methyl-a-D-glucopyranose (1a) in 14% and 64% yields,
respectively. The treatment of 11a using NaOMe in MeOH
quantitatively afforded 1a. The reaction using AllMgCl and
n-BuLi similarly gave the mixtures of 6-O-acetyl-1-C-allyl-
2,3,4-tri-O-benzyl-a-D-glucopyranose (11b) and 1-C-allyl-
2,3,4-tri-O-benzyl-a-D-glucopyranose (1b) in 30% and 54%
yields, and of 6-O-acetyl-2,3,4-tri-O-benzyl-1-C-n-butyl-D-
glucopyranose (11c) and 2,3,4-tri-O-benzyl-1-C-n-butyl-a-
D-glucopyranose (1c) in 64% and 12% yields, respectively.
The reactions using PhMgCl and PhCH2MgCl afforded 6-O-
acetyl-2,3,4-tri-O-benzyl-1-C-phenyl-a-D-glucopyranose
(11d) and 6-O-acetyl-1-C-benzyl-2,3,4-tri-O-benzyl-a-D-
glucopyranose (11e) in 89% and 82% yields, respectively,
with almost no production of the deacetylated compounds. It
seemed that these bulky organometallic reagents were apt to
produce the nucleophilic attack on the conformationally
fixed carbonyl group at C-1 of 10 rather than on the acetyl
group at C-6. The treatment of 11b–e using NaOMe in
MeOH quantitatively afforded 1b-e. 2,3,4-Tri-O-benzyl-1-
C-methyl-a-D-mannopyranose (6a) was similarly prepared
in 82% yield from 6-O-acetyl-2,3,4-tri-O-benzyl-D-manno-
1,5-lactone(13). Preparation of 9 and 12 was reported in the
following literature. See: (a) Koto, S.; Morishima, N.;
Takenaka, K.; Kanemitsu, K.; Shimoura, N.; Kase, M.;
Kojiro, S.; Nakamura, T.; Kawase, T.; Zen, S. Bull. Chem.
Soc. Jpn. 1989, 62, 3549. (b) Murakata, C.; Ogawa, T.
Carbohydr. Res. 1992, 235, 95. (c) The oxidation of 9 using
pyridinium chlorochromate also gave 10 in a moderate yield.
See: Horito, S.; Asano, K.; Umemura, K.; Hashimoto, H.;
Yoshimura, J. Carbohydr. Res. 1983, 121, 175.
A typical glycosidation procedure is as follows. To a stirred
solution of TfOH (0.48 mL, 0.0054 mmol) was added 1a (50
mg, 0.11 mmol) in MeCN (2 mL) at 0 °C in the presence of
dry MgSO4 (ca. 100 mg) in an Ar atmosphere. The resulting
mixture was stirred for 2 h. The reaction was then quenched
by the addition of a sat. NaHCO3 solution (5 mL). The
reaction mixture was extracted with EtOAc, and the organic
layer was washed with H2O and a sat. NaCl solution. After
the organic layer was dried over Na2SO4, the solvent was
evaporated under reduced pressure. The crude product was
purified by preparative silica gel TLC (EtOAc–hexane =
1:2) to give 2a (45 mg, 93%).
Compound 2a: [a]D23 –47.7 (c 1.54, CHCl3). 1H NMR (600
MHz, CDCl3): d = 1.49 (3 H, s, H-2¢), 3.23 (1 H, s, H-4), 3.31
(1 H, s, H-2), 3.59 (1 H, s, H-3), 3.75 (1 H, dd, J = 6.2 Hz,
J = 6.9 Hz, H-7a), 3.96 (1 H, d, J = 6.9 Hz, H-7b), 4.34–4.39
(3 H, m, OCH2Ph and OCHaHbPh), 4.53 (1 H, m,
OCHaHbPh), 4.53 (1 H, d, J = 6.2 Hz, H-1), 4.58–4.61 (2 H,
m, OCH2Ph). 13C NMR (150 MHz, CDCl3): d = 21.0 (C-2¢),
65.5 (C-7), 71.0 (OCH2Ph), 71.2 (OCH2Ph), 72.3 (OCH2Ph),
74.5 (C-2), 75.2 (C-3), 75.7 (C-1), 77.3 (C-4), 107.0 (C-5).
HRMS (ESI): m/z calcd for C28H30O5Na+: 469.1991; found:
469.2032.
Compound 2b: [a]D23 +7.6 (c 4.57, CHCl3). 1H NMR (600
MHz, CDCl3): d = 2.56 (1 H, dd, J = 7.6 Hz, J = 14.4 Hz, H-
2¢a), 2.64 (1 H,dd, J = 7.6 Hz, J = 14.4 Hz, H-2¢b), 3.24 (1
H, s, H-4), 3.26 (1 H, s, H-2), 3.54 (1 H, s, H-3), 3.66 (1 H,
dd, J = 6.2 Hz, J = 6.9 Hz, H-7a), 3.94 (1 H, d, J = 6.9 Hz,
H-7b), 4.29–4.34 (3 H, m, OCH2Ph and OCHaHbPh), 4.41–
4.52 (3 H, m, OCH2Ph and OCHaHbPh), 4.56 (1 H, d,
J = 5.5 Hz, H-1), 5.03–5.05 (2 H, m, H-4¢), 5.77 (1 H, m, H-
3¢). 13C NMR (150 MHz, CDCl3): d = 38.1 (C-2¢), 65.7 (C-
7), 70.9 (OCH2Ph), 71.5 (OCH2Ph), 72.2 (OCH2Ph), 74.6
(C-2), 74.9 (C-3), 75.5 (C-1), 76.2 (C-4), 107.2 (C-5), 118.4
(C-4¢), 132.0 (C-3¢). HRMS (ESI): m/z calcd for
C30H32O5Na+: 495.2147; found: 495.2195.
Compound 2c: [a]D23 –36.7 (c 1.08, CHCl3). 1H NMR (600
MHz, CDCl3): d = 0.84 (3 H, t, J = 6.9 Hz, H-5¢), 1.16 (1 H,
m, H-3¢a), 1.25 (2 H, m, H-4¢), 1.36 (1 H, m, H-3¢b), 1.75 (1
H, m, H-2¢a), 1.90 (1 H, ddd, J = 13.1 Hz, J = 3.4 Hz,
J = 13.7 Hz, H-2¢b), 3.25 (1 H, s, H-4), 3.31 (1 H, s, H-2),
(10) (a) Boon, G.-J.; Isles, S.; Setala, P. Synlett 1995, 755.
(b) Bernlind, C.; Oscarson, S. J. Org. Chem. 1998, 63, 7780.
(11) Grindley, T. B. Glycoscience: Chemistry and Chemical
Biology I; Fraser-Reid, B.; Tatsuta, K.; Thieme, J., Eds.;
Springer: Berlin, 2001, 4–51.
Synlett 2005, No. 19, 2973–2977 © Thieme Stuttgart · New York