686
Vol. 53, No. 6
Et2O (100 ml), and the reaction mixture was stirred for 1.75 h at room tem-
perature. The reaction mixture was treated with acetone (6 ml) and H2O, and
extracted with Et2O. The organic layer was washed with brine and dried over (3H, s), 2.40 (1H, dd, Jꢂ15.0, 10.0 Hz), 2.91 (1H, qdd, Jꢂ6.0, 10.0, 6.0 Hz),
MgSO4. Evaporation of the organic solvent gave a crude residue, which was 2.94 (1H, dd, Jꢂ15.0, 6.0 Hz), 3.59 (1H, d, Jꢂ14.0 Hz), 3.62 (1H, d,
less oil.
IR (KBr) cmꢃ1: 3404, 1608, 1509, 1243. H-NMR d: 0.98 (3H, s), 2.23
1
chromatographed on silica gel (195 g, hexane/AcOEtꢂ5 : 1) to give 8
(9.26 g, 99%) as a colorless oil.
Jꢂ14.0 Hz), 6.71 (2H, d, Jꢂ8.0 Hz), 6.98 (2H, d, Jꢂ8.0 Hz), 7.18—7.31
(5H, m). Anal. Calcd for C17H21NO: C, 79.96; H, 8.29; N, 5.49. Found: C,
79.56; H, 8.38; N, 5.46. FAB-MS (m/z): [MꢁH]ꢁ 256.
IR (neat) cmꢃ1: 3339, 2938, 1509. 1H-NMR d: 0.18 (6H, s), 0.97 (9H, s),
1.54 (1H, s), 2.78 (2H, t, Jꢂ6.0 Hz), 3.79 (2H, t, Jꢂ6.0 Hz), 6.77 (2H, d,
Methyl 1,2,3,4-Tetraacetyl-a- and b-D-glucopyranuronates (15, 16)
Jꢂ8.0 Hz), 7.06 (2H, d, Jꢂ8.0 Hz). Anal. Calcd for C14H24SiO2: C, 66.61; A solution of glucuronolactone (14; 8.0 g, 45 mmol) and Et3N (0.8 ml) in
H, 9.58. Found: C, 66.80; H, 9.69. FAB-MS (m/z): Mꢁ 252.
MeOH (60 ml) was stirred for 2 h at room temperature, and then MeOH was
2-(4-tert-Butyldimethylsiloxyphenyl) Acetaldehyde (9) A solution of
removed in vacuo. The resulting syrup was dissolved in pyridine (20 ml) and
8 (4.50 g, 18 mmol) in CH2Cl2 (10 ml) was added to a mixture of pyridinium acetic anhydride (30 ml). The mixture was allowed to stand in the refrigera-
chlorochromate (PCC; 7.76 g, 36 mmol) in CH2Cl2 (100 ml) and celite (18 g) tor for 5 d, then concentrated in vacuo. Et2O was added to the resulting
at 0 °C, and the reaction mixture was stirred for 5 h at the same temperature.
The reaction mixture was filtered with the aid of celite and the filtrate was 16). The mother liquor was evaporated to give a crude oil (13.82 g), which
residue, and the less soluble product was filtered to give a solid (b-isomer
concentrated in vacuo. The residue was chromatographed on silica gel
(100 g, hexane/AcOEtꢂ10 : 1) to give 9 (3.59 g) as a colorless oil.
was chromatographed on silica gel (50 g, hexane/AcOEtꢂ3 : 1) to yield 16
(6.43 g, 38%). The NMR data of 16 were identical with those of the reported
16.7) The crude oil from the mother liquor was again chromatographed on
silica gel (160 g, hexane/AcOEtꢂ4 : 1) to provide 15 (4.30 g, 25% as a-iso-
mer).
1H-NMR d: 0.18 (6H, s), 0.97 (9H, s), 3.59 (2H, d, Jꢂ2.0 Hz), 6.82 (2H,
d, Jꢂ8.0 Hz), 7.05 (2H, d, Jꢂ8.0 Hz), 9.70 (1H, t, Jꢂ2.0 Hz).
2-(4-tert-Butyldimethylsiloxyphenyl) Propanol ((ꢀ)-10) To a stirred
solution of 9 (3.59 g, 14 mmol) in Et2O (100 ml) was added dropwise 1 M
methyllithium (MeLi)–Et2O solution (14 ml, 14 mmol) at ꢃ78 °C under an
argon atmosphere. The reaction mixture was stirred for 1 h at the same tem-
perature and quenched by the addition of aqueous ammonium chloride
(NH4Cl). The mixture was extracted with Et2O and the organic layer was
15: 1H-NMR d: 1.97 (3H, s), 2.00 (3H, s), 2.00 (3H, s), 2.14 (3H, s), 3.70
(3H, s), 4.37 (1H, d, Jꢂ10.0 Hz), 5.07 (1H, dd, Jꢂ10.0, 4.0 Hz), 5.18
(1H, dd, Jꢂ10.0, 10.0 Hz), 5.47 (1H, dd, Jꢂ10.0, 10.0 Hz), 6.35 (1H, d,
Jꢂ4.0 Hz).
Methyl 2,3,4-Triacetyl-a-D-glucopyranuronate (17) (1) A mixture of
washed with brine (6 ml), and dried over MgSO4. Evaporation of the organic 15 (2.0 g, 5.3 mmol) and tributyltin methoxide (Bu3SnOMe; 1.57 ml,
solvent gave a crude residue, which was chromatographed on silica gel
5.3 mmol) in ClCH2CH2Cl (30 ml) was stirred for 5 h at 90 °C, and the
(75 g, hexane/AcOEtꢂ20 : 1) to provide 10 (1.99 g, 42%, from 8) as a color- whole mixture was evaporated to give a crude residue. It was chro-
less oil.
matographed on silica gel (70 g, hexane/AcOEtꢂ3 : 1) to give 17 (1.06 g,
60%) as a colorless oil. The NMR data of 17 were identical with those of the
reported 17.8)
IR (neat) cmꢃ1: 3361, 2934, 1509. 1H-NMR d: 0.18 (6H, s), 0.97 (9H, s),
1.20 (3H, d, Jꢂ6.0 Hz), 1.64 (1H, br s), 2.60 (1H, dd, Jꢂ8.0, 14.0 Hz), 2.69
(1H, dd, Jꢂ4.0, 14.0 Hz), 3.94 (1H, qdd, Jꢂ4.0, 6.0, 8.0 Hz), 6.77 (2H, d,
(2) A mixture of 16 (1.0 g, 2.7 mmol) and Bu3SnOMe (0.8 ml, 2.7 mmol)
Jꢂ8.0 Hz), 7.04 (2H, d, Jꢂ8.0 Hz). Anal. Calcd for C15H26SiO2: C, 67.62; in ClCH2CH2Cl (15 ml) was stirred for 2 h at 90 °C. The reaction mixture
H, 9.84. Found: C, 67.60; H, 9.98. FAB-MS (m/z): Mꢁ 266.
was worked up in the same way as for 15 to give 17 (0.90 g, 99%). The
2-(4-tert-Butyldimethylsiloxyphenyl) Propanone (11) Dimethyl sul- NMR data of 17 were identical with those of the reported 17.8)
foxide (DMSO; 1.25 g, 16 mmol) was added to a stirred solution of oxalyl
chloride ((COCl)2; 1.02 g, 8 mmol) in CH2Cl2 (40 ml) at ꢃ78 °C under
Methyl 2,3,4-Triacetyl-1-O-(trichloroacetimidoyl)-a-D-glucopyra-
nouronate (18) mixture of 17 (1.50 g, 4 mmol), K2CO3 (0.94 g,
A
argon. After 10 min, a solution of 10 (1.01 g, 4 mmol) in CH2Cl2 (8 ml) was 6.8 mmol) and molecular sieves (MS 3 Å, 0.5 g) in CH2Cl2 (5 ml) under an
added to the above mentioned reaction mixture and the mixture was kept at argon atmosphere was stirred for 25 min at 0 °C. A solution of trichloroace-
the same temperature for 1 h. Triethylamine (Et3N; 3.24 g, 32 mmol) was tonitrile (Cl3CCN; 1.73 g, 12 mmol) in CH2Cl2 (5 ml) was added to the above
added to the reaction mixture and the whole mixture was warmed to ꢃ20 °C
mentioned reaction mixture, and the whole mixture was stirred for 2 h at the
for 1 h. The whole mixture was diluted with brine (40 ml) and extracted with same temperature. The reaction mixture, including a solid, was filtered and
CH2Cl2. The organic layer was dried over MgSO4 and evaporated to give a
crude residue, which was chromatographed on silica gel (25 g,
hexane/AcOEtꢂ20 : 1) to give 11 (0.88 g, 83%) as a colorless oil.
the filtrate was treated with 7% aqueous NaHCO3, then concentrated in
vacuo. The resulting residue was chromatographed on silica gel (50 g,
hexane/AcOEtꢂ5 : 1) to give 18 (1.44 g, 75%) as a solid. The NMR data of
18 were identical with those of the reported 18.6)
IR (neat) cmꢃ1: 2938, 1715, 1509. 1H-NMR d: 0.17 (6H, s), 0.96 (9H, s),
2.10 (3H, s), 3.59 (2H, s), 6.78 (2H, d, Jꢂ8.0 Hz), 7.03 (2H, d, Jꢂ8.0 Hz).
Coupling Reaction between (ꢀ)-13 and 18 A mixture of 13 (0.1214 g,
Anal. Calcd for C15H24SiO2: C, 68.13; H, 9.15. Found: C, 68.00; H, 9.26. 0.48 mmol), 18 (0.45 g, 0.94 mmol) and MS 3 Å (0.2 g) was dried under re-
FAB-MS (m/z): [MꢁH]ꢁ 265.
duced pressure, and CH2Cl2 (10 ml) was added to the above mentioned mix-
1-(4-tert-Butyldimethylsiloxyphenyl)-2-N-benzyl-N-methylamino- ture. The whole mixture was stirred for 10 min at room temperature under an
propane ((ꢀ)-12) To solution of N-methylbenzylamine (2.04 g, argon atmosphere. Boron trifluoride ether complex (BF3·Et2O; 0.06 ml,
a
16.8 mmol) and 1.8 M HCl/MeOH solution (3.1 ml, 5.6 mmol) in MeOH
(5 ml) was added a solution of 11 (0.73 g, 2.8 mmol) in MeOH (5 ml) at
0 °C. Cyanoborohydride (NaBH3CN; 0.35 g, 5.6 mmol) was added to the
above reaction mixture, and the whole mixture was stirred for 24 h at room
temperature. The reaction mixture was treated with NaHCO3 (0.47 g) and
concentrated to give a residue. It was diluted with H2O and extracted with
Et2O. The organic layer was dried over MgSO4 and evaporated to afford
0.42 mmol) was added to the above mentioned whole mixture at 0 °C and the
reaction mixture was stirred for 3 h at room temperature. The reaction mix-
ture was filtered and the filtrate was washed with 7% aqueous NaHCO3. The
organic layer was dried over MgSO4 and evaporated to give a crude residue,
which was chromatographed on silica gel (20 g, benzene/AcOEtꢂ5 : 1) to
provide 19 (0.225 g, 97%) as a colorless oil.
IR (KBr) cmꢃ1: 1755, 1375. 1H-NMR d: 0.96 (3H, d, Jꢂ6.0 Hz), 2.22
(3H, s), 2.43 (1H, dd, Jꢂ16.0, 12.0 Hz), 2.92 (1H, dd, Jꢂ16.0, 6.0 Hz), 2.94
(1H, qdd, Jꢂ12.0, 6.0, 6.0 Hz), 3.56 (1H, d, Jꢂ14.0 Hz), 3.60 (1H, d,
a
crude residue, which was chromatographed on silica gel (60 g,
benzene/AcOEtꢂ10 : 1) to give 12 (0.15 g, 51%) as a colorless oil.
1
IR (neat) cmꢃ1: 2934, 1506, 1258. H-NMR d: 0.19 (6H, s), 0.97 (3H, d, Jꢂ14.0 Hz), 3.71 (3H, s), 4.15 (1H, d, Jꢂ10.0 Hz), 5.09 (1H, d, Jꢂ8.0 Hz),
Jꢂ5.0 Hz), 0.98 (9H, s), 2.22 (3H, s), 2.42 (1H, dd, Jꢂ16.0, 12.0 Hz), 2.91 5.22—5.28 (1H, m), 5.29—5.35 (2H, m), 6.88 (2H, d, Jꢂ8.0 Hz), 7.05 (2H,
(1H, dd, Jꢂ16.0, 6.0 Hz), 2.94 (1H, qdd, Jꢂ12.0, 6.0, 6.0 Hz), 3.56 (1H, d, d, Jꢂ8.0 Hz), 7.17—7.30 (5H, m). Anal. Calcd for C30H37NO10: C, 63.04; H,
Jꢂ14.0 Hz), 3.60 (1H, d, Jꢂ14.0 Hz), 6.74 (2H, d, Jꢂ8.0 Hz), 6.99 (2H, d, 6.52; N, 2.45. Found: C, 63.26; H, 6.71; N, 2.19. FAB-MS (m/z): [MꢁH]ꢁ
Jꢂ8.0 Hz), 7.18—7.31 (5H, m). Anal. Calcd for C23H35SiNO: C, 74.74; H, 572.
9.54; N, 3.79. Found: C, 74.55; H, 9.68; N, 3.51. FAB-MS (m/z): [MꢁH]ꢁ
370.
Methyl 1-O-(4-Hydroxymethamphetaminyl)-a-D-glucopyranouronate
(5) A solution of 19 (0.1875 g, 0.3 mmol) and 1 M NaOH solution (2.4 ml)
1-(4-Hydroxyphenyl)-2-N-benzyl-N-methylaminopropane ((ꢀ)-13) in MeOH (3 ml) was stirred for 1.5 h at 0 °C, and the reaction mixture was
A solution of 12 (0.60 g, 1.6 mmol) and 1 M H2SO4 solution (4 ml) in MeOH
(8 ml) was stirred for 3.5 h at room temperature, then the reaction mixture
was treated with NaHCO3 (0.21 g). The reaction mixture was diluted with
H2O and extracted with Et2O. The organic layer was dried over MgSO4 and
evaporated in vacuo to provide a residue, which was chromatographed on
silica gel (30 g, benzene/AcOEtꢂ20 : 1) to give 13 (0.34 g, 83%) as a color-
acidified with 1 M HCl (3 ml). The whole mixture was stirred for 20 min at
0 °C and evaporated in vacuo. The resulting residue was dissolved in MeOH
and the precipitate was filtered. The filtrate was concentrated in vacuo to
provide a residue which was dissolved in MeOH (2 ml). The MeOH solution
was subjected to hydrogenolysis in the presence of 10% palladium hydrox-
ide on carbon (Pd(OH)2–C; 0.1 g) for 12 h at ambient temperature. The reac-