´
M. B. Cid, J. B. Bonilla, F. Alfonso, M. Martın-Lomas
FULL PAPER
(d, J ϭ 3.5 Hz, 1 H, H1Ј), 4.90 (AB, J ϭ 11.0 Hz, 1 H, CH-Ph), washed with water and finally lyophilized to give the fully depro-
4.83 (AB, J ϭ 1.0 Hz, 1 H, CH-Ph), 4.68 (AB, J ϭ 11.0 Hz, 1 H, tected pseudodissacharide XII (6.1 mg, 0.02 mmol, 95%). Rf
CH-Ph), 4.49 (m, 2 H, H2, C2OH), 4.48 (m, 1 H, H2), 4.39 (AB,
(EtOAc/MeOH/H2O/AcOH, 2:2:1:1): 0.34. [α]2D0 ϭ ϩ38 (c ϭ 0.2,
1
J ϭ 11.0 Hz, 1 H, CH-Ph), 4.25Ϫ4.20 (m, 2 H, H3, CH-Ph), 3.99 H2O). H NMR (500 MHz, D2O): δ ϭ 5.36 (d, J ϭ 3.8 Hz, 1 H,
(t, J ϭ 10.0 Hz, 1 H, H3Ј), 3.88 (AB, J ϭ 11.0 Hz, 1 H, CH-Ph),
3.73Ϫ3.66 (m, 2 H, H4Ј, H5Ј), 3.60 (dd, JH2Ј-H3Ј ϭ 10.0, JH2Ј-H1Ј
H1Ј), 4.04 (dt, JH5Ј-H4Ј ϭ 10.0, JH5Ј-H6aЈ ϭ JH5-H6bЈ ϭ 3.0 Hz, 1 H,
H5Ј), 3.99 (t, J ϭ 3.5 Hz, 1 H, H6), 3.96 (t, J ϭ 3.5 Hz, 1 H, H1),
ϭ
3.5 Hz, 1 H, H2Ј), 3.22 (br. d, J ϭ 11.2 Hz, 1 H, H6aЈ), 2.69 (br. d, 3.92 (dd, JH2ϪH3 ϭ 9.5, JH2ϪH1 ϭ 3.5 Hz, 1 H, H2), 3.82 (t, J ϭ
J ϭ 11.2 Hz, 1 H, H6bЈ) ppm. 13C NMR (125 MHz, CDCl3): δ ϭ
10.0 Hz, 1 H, 1 H, H3Ј), 3.80 (m, 2 H, H6aЈ, H6bЈ), 3.74 (dd,
165.8, 165.5, 165.1, 164.7 (4 CO), 138.0 (C, Ph), 137.6 (2 C, Ph), JH5ϪH4 ϭ 9.5, JH5ϪH6 ϭ 3.5 Hz, 1 H, H5), 3.66 (t, J ϭ 9.5 Hz, 1
133.8Ϫ133.2 (4 CHpara, Bz), 130.1Ϫ127.9 (35 C, Bz, Ph), 100.4
H, H3), 3.62 (t, J ϭ 9.5 Hz, 1 H, H4), 3.50 (t, J ϭ 10.0 Hz, 1 H,
(C1Ј), 83.2 (C3), 80.9 (C3Ј), 77.7 (C4Ј), 75.7, 74.7, 73.4 (3 CH2Ph), H4Ј), 3.16 (dd, JH2Ј-H3Ј ϭ 10.5, JH2Ј-H1Ј ϭ 3.8 Hz, 1 H, H2Ј) ppm.
72.0 (C5Ј), 70.9 (C2), 70.7 (C5), 70.6 (C4), 69.7 (C1), 68.6 (C6), 67.0 13C NMR (D2O, 125 MHz): δ ϭ 97.1 (C1Ј), 80.2 (C3), 71.7 (C5Ј),
(C6Ј), 64.6 (C2Ј) ppm. C61H55N3O14 (1054.121): calcd. C 69.50, H 71.4 (C1), 70.9 (C6), 70.7 (C4), 70.6 (C3Ј), 70.5 (C5), 70.1 (C2), 68.9
5.26, N 3.99 found C 69.55, H 5.25, N 3.99. HR-FABMS: calcd.
(C4Ј), 59.6 (C6Ј), 54.2 (C2Ј) ppm. HR-FABMS: calcd. for
for [C61H55N3O14 ϩ Na]ϩ, 1076.3582; found, 1076.3616; Data for [C12H23NO10 ϩ Na]ϩ, 364.1220; found, 364.1225.
6: M.p. 122Ϫ126 °C; Rf (toluene/acetone, 3:1): 0.51. [α]2D0 ϭ Ϫ39
1
2-Azido-2-deoxy-3,4,6-tri-O-benzyl-
1,4,5,6-tetra-O-benzoyl- -chiro-inositol (8a) and 2-Azido-2-deoxy-
3,4,6-tri-O-benzyl- -galactopyranosyl-α-(1Ǟ2)-1,4,5,6-tetra-O-
benzoyl- -chiro-inositol (9a). These pseudodisaccharides were pre-
D-galactopyranosyl-α-(1Ǟ3)-
(c ϭ 1.0, CHCl3). H NMR (500 MHz, CDCl3): δ ϭ 8.13 (d, J ϭ
8.0 Hz, 2 H, Hortho), 8.02 (m, 4 H, Hortho), 7.76 (d, J ϭ 8.0 Hz, 2
H, Hortho), 7.64 (t, J ϭ 8.0 Hz, 2 H, Hpara), 7.55Ϫ7.00 (m, 25 H,
Bz, Ph), 6.01 (t, J ϭ 9.8 Hz, 1 H, H4), 5.93 (t, J ϭ 4.0 Hz, 1 H,
H6), 5.82 (m, 2 H, H1, H5), 5.24 (d, J ϭ 3.5 Hz, 1 H, H1Ј), 4.68
(AB, J ϭ 10.5 Hz, 1 H, CH-Ph), 4.65 (AB, J ϭ 11.5 Hz, 1 H, CH-
Ph), 4.61 (AB, J ϭ 10.5 Hz, 1 H, CH-Ph), 4.57 (AB, J ϭ 12.0 Hz,
1 H, CH-Ph), 4.49 (td, JH3ϪH2 ϭ JH3-H4 ϭ 9.8, JH3-OH ϭ 2.0 Hz,
1 H, H3), 4.42 (AB, J ϭ 11.2 Hz, 1 H, CH-Ph), 4.35 (AB, J ϭ
12.0 Hz, 1 H, CH-Ph), 4.22 (dd, JH2ϪH3 ϭ 9.8, JH2ϪH1 ϭ 3.5 Hz,
1 H, H2), 3.88 (d, J ϭ 2.0 Hz, 1 H, C3OH), 3.80 (br. d, 1 H, J ϭ
9.5 Hz, H6aЈ), 3.73Ϫ3.61 (m, 4 H, H3Ј, H4Ј, H5Ј,H6aЈ), 3.54 (dd, JH2Ј-
L
D
L
pared from 4a (62 mg, 0.10 mmol, 1.2 equiv.) and 2 (50 mg,
0.08 mmol, 1 equiv.) as described for the preparation of 5, stirring
the reaction mixture for 1 h at Ϫ40 °C, 2 h between Ϫ40 °C and
Ϫ30 °C and then overnight at room temperature, yielding 8a
(37 mg, 0.04 mmol, 42%) and 9a (5 mg, 0.005 mmol, 6%) after flash
chromatography (toluene/acetone, 40:1). Data for 8a: Rf (toluene/
acetone, 15:1): 0.48. [α]2D0 ϭ Ϫ5 (c ϭ 1.0, CHCl3). 1H NMR
(500 MHz, CDCl3): δ ϭ 8.14 (d, J ϭ 8.0 Hz, 2 H, Hortho), 8.06 (d,
J ϭ 7.5 Hz, 2 H, Hortho), 7.99 (d, J ϭ 7.2 Hz, 2 H, Hortho), 7.72 (d,
J ϭ 8.0 Hz, 2 H, Hortho), 7.63 (m, 2 H, Hpara), 7.52 (m, 4 H, Hmeta),
7.46 (t, J ϭ 7.2 Hz, 1 H, Hpara), 7.41Ϫ6.98 (m, 20 H, Bz, Ph), 6.02
(t, J ϭ 10.0 Hz, 1 H, H4), 5.88 (br. t, J ϭ 3.5 Hz, 1 H, H6), 5.83
ϭ 9.5, JH2Ј-H1Ј ϭ 3.5 Hz, 1 H, H2Ј) ppm. 13C NMR (125 MHz,
H3Ј
CDCl3): δ ϭ 166.1, 165.6, 165.0, 164.7 (4 CO), 138.0, 137.7, 137.5
(3 C, Ph), 138.1, 137.7, 137.6, 137.5 (4 CHpara, Bz) 130.1Ϫ127.3
(35 C, Bz, Ph), 100.9 (C1Ј), 80.7 (C2, C3Ј), 77.8 (C4Ј), 75.5, 74.4,
73.5 (3 CH2Ph), 71.9 (C3), 71.8 (C5Ј), 71.5 (C4), 70.0, 69.8 (C1, C5),
68.7 (C6), 67.6 (C6Ј), 64.3 (C2Ј) ppm. C61H55N3O14 (1054.121):
calcd. C 69.50, H 5.26, N 3.99 found C 69.35, H 5.39, N 4.08. HR-
FABMS: calcd. for [C61H55N3O14 ϩ Na]ϩ, 1076.3582; found,
1076.3602.
(br. t, J ϭ 3.5 Hz, 1 H, H1), 5.79 (dd, JH5ϪH4 ϭ 10.5, JH5ϪH6
ϭ
3.5 Hz, 1 H, H5), 5.16 (d, J ϭ 3.5 Hz, 1 H, H1Ј), 4.72Ϫ4.64 (m, 3
H, CH-Ph, CH2-Ph), 4.45 (m, 1 H, H2), 4.36 (AB, J ϭ 11.5 Hz, 1
H, CH-Ph), 4.21 (t, J ϭ 9.5 Hz, 1 H, H3), 4.08 (dd, JH2Ј-H3Ј ϭ 10.0,
JH2Ј-H1Ј ϭ 3.0 Hz, 1 H, H2Ј), 4.02Ϫ3.89 (m, 3 H, H3Ј, H4Ј, H5Ј) 3.28
(t, J ϭ 8.5 Hz, 1 H, H6aЈ), 2.72 (dd, JH6bЈ-H6aЈ ϭ 8.5 Hz, JH6bЈ-
2-Azido-2-deoxy-3,4,6-tri-O-benzyl-
D
-glucopyranosyl-α(1Ǟ3)-
L
-
ϭ 8.0 Hz, 1 H, H6bЈ) ppm. 13C NMR (CDCl3, 125 MHz): δ ϭ
H6aЈ
chiro-inositol (7): MeONa in MeOH (2 , 7 mL) was added at room
166.0, 165.6, 165.2, 164.9 (4 CO), 138.4, 137.8, 137.6 (3 C, Ph),
temperature to a solution of 5 (101 mg, 0.10 mmol, 1.0 equiv.) in 133.9Ϫ133.4 (4 CHpara, Bz), 130.2Ϫ127.8 (31 CH, Bz, Ph), 100.2
MeOH (10 mL). The solution was stirred overnight and then it was
quenched with Amberlite IRA-120 resin. The solvent and BzOMe
were evaporated by heating at 50 °C under vacuum to provide the
solid 7 (61 mg, 0.1 mmol, quantitative). M.p. 148Ϫ152 °C; Rf (ace-
(C1Ј), 82.7 (C3), 78.4 (C3Ј), 70.0 (CH2Ph), 73.2 (C4Ј), 72.8, 72.1 (2
CH2Ph), 70.9 (C2), 70.5 (C5), 70.1, 70.0 (C1, C5Ј), 68.7 (C6), 67.5
(C6Ј), 61.2 (C2Ј) ppm. C61H55N3O14 (1054.121): calcd. C 69.50, H
5.26, N 3.99 found C 69.51, H 5.12, N 4.13. HR-FABMS: calcd.
tone): 0.61. [α]2D0 ϭ ϩ67 (c ϭ 0.6, MeOH). 1H NMR (400 MHz, for [C61H53N3O14 ϩ Na]ϩ, 1076.3592; found, 1076.3585. Some of
[D6]acetone): δ ϭ 7.37Ϫ7.24 (m, 15 H, Ph), 5.44 (d, J ϭ 3.6 Hz, 1 the most significant data for 9a: 1H NMR (500 MHz, CDCl3): δ ϭ
H, H1Ј), 4.88 (AB, 2 H, 2 CH-Ph), 4.80 (AB, J ϭ 10.8 Hz, 1 H,
CH-Ph), 4.64 (AB, J ϭ 10.8 Hz, 1 H, CH-Ph), 4.56 (AB, 2 H, 2
CH-Ph), 4.38 (m, 1 H, H5Ј), 4.02Ϫ3.92 (m, 5 H, H1, H6, H4, H5,
H3Ј), 3.80Ϫ3.63 (m, 5 H, H2, H3, H4Ј, H6aЈ, H6bЈ), 3.42 (dd, 1 H,
5.26 (d, J ϭ 5.3 Hz, 1 H, H1Ј), 3.91 (br. s, 1 H, H4Ј), 3.75 (dd, JH3Ј-
ϭ 9.5, JH3Ј-H4Ј ϭ 2.5 Hz, 1 H, H3Ј) ppm.
H2Ј
2-Azido-3,4,6-tri-O-benzyl-D-galactopyranosyl-α(1Ǟ3)-L-chiro-
JH2ЈH3Ј ϭ 10.0, JH2Ј-H1Ј ϭ 3.6 Hz, H2Ј), 2.82 (s, 5 H, OH) ppm. 13
C
inositol (10a): This compound was prepared from the fully pro-
tected pseudodisaccharide 8a (29 mg, 0.03 mmol, 1.0 equiv.), using
the procedure described for the preparation of 7, to yield 10a
(18 mg, 0.03 mmol, quantitative). Rf (acetone): 0.33. [α]2D0 ϭ ϩ9
NMR (100 MHz, [D6]acetone): δ ϭ 139.4 (3 C, Ph), 130.5Ϫ129.6
(15 CH, Ph), 98.0 (C1Ј), 81.0, 79.5 (C3, C2), 75.4, 75.3, 73.7 (3
CH2Ph), 73.1, 72.7, 72.6, 72.4, 72.3, 72.2 (C1, C4, C5, C6, C3Ј, C4Ј),
71.3, (C5Ј), 69.6 (C6Ј), 64.7 (C2Ј) ppm. C33H39N3O10 (637.688):
calcd. C 62.16, H 6.165, N, 6.589; found C 61.68, H 6.043, N 6.236.
HR-FABMS: calcd. for [C33H39N3O10 ϩ Na]ϩ, 660.2533; found,
660.2543.
1
(c ϭ 0.9, CHCl3). H NMR (500 MHz, CDCl3): 7.40Ϫ7.17 (m, 15
H, 3Ph), 4.99 (d, J ϭ 4.0 Hz, 1 H, H1Ј), 4.83 (AB, J ϭ 11.5 Hz, 1
H, CH-Ph), 4.71 (s, 2 H, CH2Ph), 4.49 (AB, J ϭ 11.5 Hz, 1 H, CH-
Ph), 4.46 (AB, J ϭ 11.5 Hz, 1 H, CH-Ph), 4.39 (AB, J ϭ 11.5 Hz, 1
H, CH-Ph), 4.15Ϫ4.10 (m, 3 H, H1, H2Ј, H6), 4.07 (dd, JH5Ј-H6aЈ
ϭ
2-Amino-2-deoxy-
Compound 7 (12 mg, 0.02 mmol, 1.0 equiv.) and 10% Pd/C (5 mg, H4Ј ϭ 2.5 Hz, 1 H, H3Ј), 3.87 (dd, JH2ϪH3 ϭ 10.0, JH2ϪH1 ϭ 3.0 Hz,
0.04 mmol) were stirred overnight in ethanol/water (4:1) under a
1 H, H2), 3.82 (d, JH4Ј-H3Ј ϭ 2.5 Hz, 1 H, H4Ј), 3.78 (dd, JH5ϪH4 ϭ
hydrogen atmosphere. The slurry was filtered through celite and 9.2, JH5ϪH6 ϭ 2.5 Hz, 1 H, H5), 3.59 (m, 2 H, H4, H6aЈ), 3.51 (t, J ϭ
D-glucopyranosyl-α(1Ǟ3)-L
-chiro-inositol (XII): 9.2, JH5Ј-H6bЈ ϭ 3.0 Hz, 1 H, H5Ј), 3.90 (dd, JH3Ј-H2Ј ϭ 9.5, JH3Ј-
3510
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2003, 3505Ϫ3514