188
K. Ikeda et al./Carbohydrate Research 312 (1998) 183±189
puri®ed by silica gel chromatography using 100:1
CH2Cl2±MeOH to give 2 (34 mg, 98% from the
silica gel column chromatography using (10:1)
CH2Cl2±MeOH to give 11 (12 mg, 45%), [ꢃ]d +42ꢀ
(c 0.34, CHCl3); ꢄmax 1744 (AcO), 1636, and
1559 cm 1 (CONH); 1H NMR (CDCl3): ꢀ 1.47 (s, 9
H, t-BuOCO), 1.98, 1.99 (s, each 3 H, AcNH), 2.14
(s, 6 H, AcO), 3.32 (ddd, 1 H, J8,9a 7.8, J9a,9b
14.0 Hz, H-9a), 3.81 (s, 3H, CO2Me), 4.04, 4.13 (d,
each 1 H, Jgem 16.5 Hz, t-BuOCOCH2O±), 4.16
(ddd, 1 H, J4,5 7.3 J5,6 8.4 J5,NH 8.4 Hz, H-5), 4.33
(dd, 1H, J3,4 3.0 Hz, H-4), 4.43 (dd, 1 H, J6,7
3.5 Hz, H-6), 5.11 (ddd, 1 H, J7,8 4.6 Hz, H-8), 5.43
(dd, 1 H, H-7), 6.10 (d, 1 H, J 8.4 Hz, AcNH), 6.15
(d, 1 H, H-3), 6.65 (t, 1 H, J 6.0 Hz, AcNHCH2±).
Positive f.a.b.-m.s. (NBA): (M+H)+ m/z 545,
(M+Na)+ 567.
ꢀ
triol) as a white powder, m.p. 85±87 C, [ꢃ]d 62ꢀ
(c 0.54, CHCl3); ꢄmax 2100 (N3), 1735 (AcO), 1654,
and 1542 cm 1 (CONH); 1H NMR (CDCl3): ꢀ 1.50
(s, 9 H, t-BuOCO), 1.99 (s, 3 H, AcNH), 2.10, 2.14
(s, each 3 H, OAc), 2.76 (dd, 1 H, J3ax,3eq 14.0,
J3ax,4 3.8 Hz, H-3eq), 3.33 (dd, 1 H, J8,9a 9.2, J9a,9b
13.2 Hz, H-9a), 3.64 (s, 3 H, CO2Me), 3.66 (dd, 1
H, J8,9b 2.2 Hz, H-9b), 3.89±3.97 (m, 2 H, H-4, H-
5), 3.86, 4.03 (d, each 1 H, Jgem 17.3 Hz, t-BuO-
COCH2O±), 4.54 (dd, 1H, J5,6 9.9, J6,7 2.2 Hz, H-
6), 4.81 (ddd, 1 H, J7,8 1.9 Hz, H-8), 5.41 (dd, 1H,
H-7), 6.14 (d, 1 H, J5,NH 8.1 Hz, AcNH), 7.38±7.44
(m, 5 H, PhS-). Positive f.a.b.-m.s. (NBA):
(M+H)+ m/z 639, (M+Na)+ 661.
Methyl 5,9-diacetamido-7,8-di-O-acetyl-2,6-an-
hydro-3,5,9-trideoxy-4-O-methoxycarbonyl-d-gly-
cero-d-galacto-non-2-enonate (12).ÐCompound 11
(12 mg, 0.02 mmol) was added to a solution of
Methyl 5-acetamido-7,8-di-O-acetyl-2,6-anhydro-
9-azido-4-O-tert-butoxycarbonylmethyl-3,5,9-tri-
deoxy-d-glycero-d-galacto-non-2-enonate (10).Ð
To a solution of compound 2 (32 mg, 0.05 mmol)
and MS 4 A (0.3 g) in dry CH2Cl2 (2 mL) was
added NBS (27 mg, 0.15 mmol) and I2 (38 mg,
0.15 mmol) and TBAOTf (10 mg, 0.025 mmol) at
15 ꢀC under Ar. After stirring for 1 h at the same
temperature, to the mixture was added a solution
of DBU (23 mg, 0.15 mmol) in dry CH2Cl2
ꢀ
CF3CO2H±CH2Cl2 (1:2) (1.5 mL) at 0 C, and the
mixture was stirred for 15 h at room temperature.
After removal of the solvent, the residue was pur-
i®ed by silica gel column chromatography using
(5:1) CH2Cl2±MeOH to give 12 (13 mg, quant.); 1H
NMR (CDCl3): ꢀ 2.03, 2.12, 2.34 (s, 12H, AcO,
AcNH), 3.82 (s, 3H, CO2Me), 4.10±4.45 (m, 5 H,
H-4, 5, 6, 9), 5.12 (m, 1 H, H-8), 5.44 (br s, 1 H, H-
7), 6.13 (br s, 1 H, H-3). Positive f.a.b.-m.s. (NBA):
(M+H)+ m/z 489, (M+Na)+ 511.
ꢀ
(0.5 mL) at 15 C, and the mixture was stirred
overnight at room temperature. The suspension
was ®ltered through Celite 545 and the ®ltrate was
successively washed with aqueous 5% Na2S2O3,
and brine, dried (MgSO4), and concentrated. The
residue was puri®ed by silica gel chromatography
using 20:1 CH2Cl2±MeOH to give 10 (13 mg, 49%)
as a syrup, [ꢃ]d +42ꢀ (c 0.94, CHCl3); ꢄmax 2100
5,9 - diacetamido - 2,6 - anhydro - 4 - O - carbamoyl-
methyl-3,5,9-trideoxy-d -glycero-d -galacto-non-
enonic acid (1).ÐCompound 12 (12 mg, 0.02 mmol)
was dissolved in oxayl chloride (0.5 mL), and the
ꢀ
mixture was heated at 40±50 C for 0.5 h. After
coevaporation with toluene, the residue was dis-
solved in CH2Cl2 (1.0 mL) and to the mixture was
1
(N3), 1750 (AcO), 1655, and 1560 cm (CONH);
1H NMR (CDCl3): ꢀ 1.47 (s, 9 H, t-BuOCO), 2.00
(s, 3 H, AcNH), 2.09, 2.15 (s, each 3 H, AcO), 3.48
(dd, 1 H, J8,9a 7.8, J9a,9b 13.5 Hz, H-9a), 3.81 (s, 3
H, CO2Me), 4.09 (ddd, 1 H, J4,5 6.6, J5,6 8.6, J5,NH
8.4 Hz, H-5), 4.35 (dd, 1 H, J3,4 3.0 Hz, H-4), 4.43
(dd, 1 H, J6,7 3.5 Hz, H-6), 5.24 (ddd, 1 H, J7,8
3.8 Hz, H-8), 5.50 (dd, 1 H, H-7), 5.90 (s, 1H,
AcNH), 6.14 (d, 1 H, H-3). Positive f.a.b.-m.s.
(NBA): (M+H)+ m/z 529.
ꢀ
added 28% aqueous NH4OH (1.0 mL) at 0 C.
After stirring for 2 h, the solvent was evaporated to
dryness, the residue was dissolved in H2O (1.0 mL)
and the mixture was treated with Dowex 50W-X8
(Na+), the resin was ®ltered o through Celite 545,
and the ®ltrate was evaporated to dryness. The
residue was puri®ed by silica gel column chroma-
tography using (65:35:5) CHCl3±MeOH±H2O to
give 1 (7 mg, quant.) as a powder; 1H NMR (D2O):
ꢀ 2.01 (s, 3 H, NH), 3.20±3.28 (m, 2 H, H-7 and H-
9a), 3.54±3.78 (m, 2 H, H-8 and H-9b), 3.92±4.03
(m, 1 H, H-5), 4.10, 4.21 (d, each 1 H, Jgem 15.4 Hz,
H2NCOCH2O±), 4.33±4.45 (m, 2 H, H-4 and H-6),
6.02 (d, 1 H, J 2.4 Hz, H-3). Positive f.a.b.-m.s.
(glycerol-thioglycerol (1:2)): m/z 455 (M+2Na)+,
451 (M+ K+H)+.
Methyl 5,9-diacetamido-7,8-di-O-acetyl-2,6-an-
hydro-4-O-tert-butoxycarbonylmethyl-3,5,9-trideoxy-
d-glycero-d-galacto-non-2-enonate (11).ÐCom-
pound 10 (26 mg, 0.05 mmol) was dissolved in a
solution of thioacetic acid (7.4 mg, 0.10 mmol) in
pyridine (1.0 mL) under argon. The mixture was
stirred for 15 h at room temperature. After eva-
poration of the solvent, the residue was puri®ed by