May 2002
603
Experimental
CH2Cl2 (1 ml), cooled to 0 °C, was added CF3COOH (1 ml), and the mixture
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Optical rotations were determined with a JASCO digital polarimeter. H- was stirred for 1 h at room temperature and concentrated. Ethyl acetate and
and 13C-NMR spectra were recorded on a JNM A 500 FT NMR spectrome- toluene (1 : 2) were added and evaporated to give the 1-hydroxy compound.
ter in CDCl3 with Me4Si as the internal standard. Matrix-assisted laser des- To a solution of the residue in CH2Cl2 (2 ml) cooled at 0 °C were added
orption ionization-time of flight mass spectrometer (MALDI-TOF-MS) was trichloroacetonitlile (161 ml, 1.2 mmol) and DBU (6.9 ml, 0.05 mmol). The
recorded on a Perceptive Voyager RP mass spectrometer. TLC was per- mixture was stirred for 30 min at 0 °C. After completion of the reaction, the
formed on Silica gel 60 F254 (E. Merck) with detection by quenching of UV mixture was concentrated. Column chromatography of the residue on silica
fluorescence and by spraying with 10% H2SO4. Column chromatography gel (3 : 1 hexane–ethyl acetate) gave 10 (28 mg, quant.); [a]D24 ϩ10.3°
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was carried out on silica gel 60 (E. Merck). Octyl 4,6-O-benzylidene-2,3-di- (cϭ0.7, CHCl3); H-NMR (CDCl3) d: 8.54 (1H, s, NH), 7.67—6.85 (14H,
O-benzyl-b-D-glucopyranoside (3), 2-(trimethylsilyl)ethyl 2-deoxy-2-phthal- m, Phϫ3), 6.41 (1H, d, J1,2ϭ8.5 Hz, H-1), 4.90, 4.83, 4.67, 4.50 (4H, each d,
imido-b-D-glucopyranoside (5) and ethyl 4,6-O-benzylidene-3-O-tert-butyl
diphenylsilyl-2-O-p-methoxybenzyl-1-thio-a-D-mannopyranoside (11) were
prepared by literature method.25—27)
Jgemϭ10.9 Hz, benzyl methyleneϫ2), 4.45—4.43 (3H, m, H-2, H-3, H-6a),
4.32 (1H, dd, H-6b), 3.89 (1H, q, H-5), 3.77 (1H, t, H-4), 1.24 (9H, t,
C(CH3)3).
Octyl 2,3,6-Tri-O-benzyl-b-D-glucopyranoside (4) To a solution of 3
(1.82 g, 3 mmol) and NaBH3CN (1.64 g, 24 mmol) in dry tetrahydrofuran
(THF) (10 ml) was added 3A MS, and the mixture was stirred for 2 h at
room temperature, then cooled to 0 °C. HCl–Et2O was added until the solu-
Octyl 4,6-O-Benzylidene-3-O-tert-butyldiphenylsilyl-b-D-mannopyra-
nosyl-(1→4)-2,3,6-tri-O-benzyl-b-D-glucopyranoside (12) To a stirred
mixture of DDQ (248 mg, 1.1 mmol) and 4A MS in dry CH2Cl2 (3 ml) were
added 11 (550 mg, 0.82 mmol), 4 (340 mg, 0.6 mmol) and 4A MS in dry
tion was acidic (pH paper, gas evolution). After 1 h, the reaction mixture was CH2Cl2 (11 ml) at 0 °C. The mixture was stirred for 10 min at 0 °C and for
poured into ice-water and extracted with CHCl3. The extract was washed se- 3 h at room temperature. The mixture was quenched with a solution of
quentially with saturated aqueous NaHCO3, dried (Na2SO4) and concen- ascorbic acid (0.7%) and NaOH (0.9%) in water (5 ml), diluted with ethyl
trated. The product was purified by silica gel column chromatography using acetate and filtered off. The filtrate was successively washed with water, sat-
6 : 1 hexane–ethyl acetate as eluent to give 4 (1.1 g, 66%).
2-(Trimethylsilyl)ethyl 6-O-Trityl-2-deoxy-2-phthalimido-b-
urated aqueous NaHCO3, dried (Na2SO4), and concentrated to give mixed
acetal. To a solution of this acetal, 2,6-di-tert-butyl-4-methyl-pyridine
D
-glucopy-
ranoside (6) To a solution of 5 (500 mg, 1.2 mmol) in pyridine (5 ml) was (DTBMP: 683 mg, 3.3 mmol) and 4A MS in dry CH2Cl2 (20 ml) were stirred
added trityl chloride (375 mg, 1.3 mmol) for 4 h at 50 °C, then concentrated. for 2 h at room temperature, then cooled to 0 °C. Methyl trifluoromethane-
The product was purified by silica gel column chromatography using 20 : 1 sulfonate (MeOTf: 340 ml, 3.1 mmol) was added to the mixture, which was
CHCl3–MeOH as eluent to give 6 (600 mg, 77%); [a]D24 Ϫ16.5° (cϭ1.0, stirred for 10 min at 0 °C and for 24 h at room temperature, then neutralized
CHCl3); 1H-NMR (CDCl3) d: 7.85—7.24 (19H, m, Phϫ4), 5.24 (1H, d, with Et3N. The mixture was filtered off and washed with water, dried
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1,2ϭ7.9 Hz, H-1), 4.30 (1H, t, H-3), 4.13 (1H, t, H-2), 3.94 (1H, q, (Na2SO4) and concentrated. The product was purified by silica gel column
–OCH2–), 3.62 (1H, t, H-4), 3.61 (1H, t, H-6a), 3.53—3.48 (2H, m, H-5, chromatography using 8 : 1 hexane–ethyl acetate as eluent to give 12 (222
–CH2–), 3.44 (1H, dd, H-6b), Ϫ0.08 (9H, s, Si(CH3)3). MALDI-TOF-MS: mg, 35%); [a]D24 ϩ11.2° (cϭ1.0, CHCl3); H-NMR (CDCl3) d: 7.66—7.14
Calcd for C38H41NO7Si: m/z 651. Found: m/z 674 [MϩNa]ϩ.
(30H, m, Phϫ6), 5.34 (1H, s, benzylidene methyne), 4.95, 4.87, 4.75, 4.68,
2-(Trimethylsilyl)ethyl 3,4-Di-O-benzyl-6-O-trityl-2-deoxy-2-phthal- 4.57, 4.30 (6H, each d, Jgemϭ10.4 Hz, benzyl methyleneϫ3), 4.41 (1H, s, H-
imido-b-D-glucopyranoside (7) To a solution of 6 (580 mg, 0.9 mmol), 1Ј), 4.33 (1H, d, 1,2ϭ7.9 Hz, H-1), 4.04 (1H, dd, 5,6aϭ10.4 Hz,
tetrabutyl ammonium bromide (88 mg, 0.27 mmol) and BnBr (0.44 ml, 3.6 6a,6bϭ4.9 Hz, H-6aЈ), 3.92 (1H, q, –OCH2–), 3.90 (1H, t, J4,5ϭ9.2 Hz, H-4Ј),
1
J
J
J
mmol) in N,N-dimethylformamide (DMF) (10 ml) was added NaH (66 mg, 3.85 (1H, t, J3,4ϭ9.2 Hz, H-3), 3.72 (1H, dd, J2,3ϭ3.7 Hz, J3,4ϭ9.8 Hz, H-3Ј),
0.27 mmol) for 2 h at 0 °C. The mixture was diluted with ethyl acetate 3.60—3.59 (2H, m, H-4, H-6b), 3.58 (1H, d, J2,3ϭ3.7 Hz, H-2Ј), 3.56 (1H, t,
(10 ml), then washed with water, dried (Na2SO4) and concentrated. The
J6a,6bϭ10.4 Hz, H-6bЈ), 3.48—3.45 (2H, m, H-5, –OCH2–), 3.38—3.35 (2H,
product was purified by silica gel column chromatography using 10 : 1 m, H-2, H-6b), 2.89 (1H, q, H-5Ј), 2.69 (1H, s, OH), 1.64 (2H, q,
hexane–ethyl acetate as eluent to give 7 (666 mg, 88%); [a]D24 ϩ5.50° –OCH2CH2–), 1.25 (10H, s, –CH2–ϫ5), 1.03 (9H, s, CH3ϫ3), 0.88 (3H, t,
(cϭ1.0, CHCl3); 1H-NMR (CDCl3) d: 7.81—6.84 (34H, m, Phϫ6), 5.20
–CH2CH3). 13C-NMR (CDCl3): d 103.7 (JCHϭ157.2 Hz, C-1), 101.1 (ben-
(1H, d, J1,2ϭ7.9 Hz), 4.80, 4.69, 4.44, 4.42 (4H, each d, Jgemϭ11.2 Hz, ben- zylidene methyne), 100.1 (JCHϭ159.3 Hz, C-1Ј), 82.8 (C-3), 81.8 (C-2), 78.1
zyl methyleneϫ2), 4.28 (1H, t, H-3), 4.26 (1H, t, H-2), 4.05—3.98 (2H, m, (C-4Ј), 78.1 (C-4), 75.4, 74.9, 74.7 (benzyl methylene), 74.3 (C-5), 72.6 (C-
H-6a, –OCH2–), 3.63 (1H, t, H-4), 3.60—3.54 (2H, m, H-5, H-6b), 3.28 3Ј), 71.4 (C-2Ј), 70.2 (–OCH2–), 68.6 (C-6), 68.5 (C-6Ј), 66.6 (C-5Ј), 31.8
(1H, q, –OCH2–), Ϫ0.07 (9H, s, Si(CH3)3). MALDI-TOF-MS: Calcd for (–OCH2CH2–), 29.8, 29.7, 29.4, 29.3 (–CH2–), 26.8 (CH3ϫ3), 26.2
C52H53NO7Si: m/z 831. Found: m/z 854 [MϩNa]ϩ.
(–CH2CH3), 14.1 (–CH2CH3). MALDI-TOF-MS: Calcd for C64H78O11Si:
2-(Trimethylsilyl)ethyl 3,4-Di-O-benzyl-2-deoxy-2-phthalimido-b-D-
glucopyranoside (8) To a solution of 7 (315 mg, 0.34 mmol) in CH2Cl2
(3 ml) and MeOH (1.5 ml) was added p-toluene sulfonic acid (146 mg,
0.68 mmol) for 20 h at room temperature. The mixture was added Et3N, and
m/z 1050. Found: m/z 1073 [MϩNa]ϩ.
Octyl 2-O-Benzyl-4,6-O-benzylidene-3-O-tert-butyldiphenylsilyl-b-D-
mannopyranosyl-(1→4)-2,3,6-tri-O-benzyl-b-D-glucopyranoside (13) To
a solution of 12 (437 mg, 0.41 mmol) and BnBr (0.10 ml, 0.8 mmol) in DMF
concentrated. The product was purified by silica gel column chromatography (5 ml) was added NaH (14.9 mg, 0.62 mmol) for 2 h at 0 °C. The mixture
using 20 : 1 benzene–acetone as eluent to give 8 (293 mg, quant.); [a]D24
was diluted with ethyl acetate (10 ml), washed with water, dried (Na2SO4)
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ϩ1.40° (cϭ1.0, CHCl3); H-NMR (CDCl3) d: 7.67—6.86 (14H, m, Phϫ3), and concentrated. The product was purified by silica gel column chromatog-
5.19 (1H, d, J1,2ϭ7.9 Hz), 4.38, 4.80, 4.73, 4.45 (4H, each d, Jgemϭ11.0 Hz, raphy using 10 : 1 hexane–ethyl acetate as eluent to give 13 (341 mg, 72%);
benzyl methyleneϫ2), 4.35 (1H, t, J3,4ϭ8.8 Hz, H-3), 4.20 (1H, t, H-2), 3.93 [a]D24 Ϫ8.71° (cϭ1.0, CHCl3); 1H-NMR (CDCl3) d: 7.65—7.12 (35H, m,
(1H, dd, H-6a), 3.87 (1H, q, –OCH2–), 3.80—3.72 (2H, m, H-4, H-6b), 3.56 Phϫ7), 5.31 (1H, s, benzylidene methyne), 4.95, 4.93, 4.92, 4.77, 4.76, 4.71,
(1H, q, H-5), 3.43 (1H, q, –OCH2–), Ϫ0.08 (9H, s, Si(CH3)3). MALDI-TOF- 4.68, 4.43 (8H, each d, Jgemϭ11.6 Hz, benzyl methyleneϫ4), 4.30 (1H, d,
MS: Calcd for C33H59NO7Si: m/z 589. Found: m/z 612 [MϩNa]ϩ.
J1,2ϭ7.9 Hz, H-1), 4.22 (1H, s, H-1Ј), 4.19 (1H, dd,
J5,6aϭ10.4 Hz,
2-(Trimethylsilyl)ethyl 3,4-Di-O-benzyl-6-O-pivaloyl-2-deoxy-2-phthal-
imido-b-D-glucopyranoside (9) To a solution of 8 (293 mg, 0.34 mmol) in
pyridine (4 ml) was added pivaloyl chloride (2 ml) for 5 h at 0 °C. The mix-
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6a,6bϭ4.88 Hz, H-6aЈ), 4.10 (1H, t, H-6a), 4.05 (1H, t, J4,5ϭ9.9 Hz, H-4Ј),
3.86 (1H, dd, J2,3ϭ3.3 Hz, J3,4ϭ12.8 Hz, H-3Ј), 3.83—3.78 (2H, m, H-6b,
–OCH2–), 3.51 (1H, d, H-2Ј), 3.46—3.45 (2H, m, H-5, –OCH2–), 3.39—3.3
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ture was diluted with MeOH (5 ml), then extracted with CHCl3, washed with (3H, m, H-2, H-4, H-6b), 3.01 (1H, q, H-5Ј), 1.55 (2H, q, –OCH2CH2–),
5% HCl, dried (Na2SO4) and concentrated. The product was purified by sil-
ica gel column chromatography using 4 : 1 hexane–ethyl acetate as eluent to
1.25 (10H, s, –CH2–ϫ5), 1.00 (9H, s, CH3ϫ3), 0.88 (3H, t, –CH2CH3). 13C-
NMR (CDCl3): d 103.5 (C-1), 102.3 (benzylidene methyne), 101.7 (C-1Ј),
give 9 (336 mg, quant.); [a]D24 ϩ0.58° (cϭ1.0, CHCl3); 1H-NMR (CDCl3) d: 84.7 (C-3), 82.3 (C-2), 79.5 (C-2Ј), 78.5 (C-4Ј), 78.1 (C-4), 75.7, 75.4, 74.9,
7.67—6.87 (14H, m, Phϫ3), 5.15 (1H, d, J1,2ϭ7.9 Hz, H-1), 4.89, 4.80,
4.64, 4.67 (4H, each d, Jgemϭ11.2 Hz, benzyl methyleneϫ2), 4.45 (1H, d, H-
74.4 (benzyl methyleneϫ4), 74.5 (C-5), 73.4 (C-2), 69.9 (–OCH2–), 68.9
(C-6), 68.5 (C-6Ј), 67.3 (C-5), 31.6 (–OCH2CH2–), 29.9, 29.7, 29.4, 29.3
6a), 4.35 (1H, t, J3,4ϭ8.5 Hz, H-3), 4.22 (1H, dd, H-6b), 4.15 (1H, t, H-2), (–CH2–), 26.8 (CH3ϫ3), 26.0 (–CH2CH3), 14.3 (–CH2CH3). MALDI-TOF-
3.86 (1H, q, –OCH2–), 3.71 (1H, q, H-5), 3.64 (1H, t, J4,5ϭ9.8 Hz, H-4), MS: Calcd for C71H84O11Si: m/z 1140. Found: m/z 1063 [MϩNa]ϩ.
3.45 (1H, q, –OCH2–), 1.26 (9H, t, C(CH3)3), Ϫ0.08 (9H, s, Si(CH3)3).
MALDI-TOF-MS: Calcd for C38H47NO8Si: m/z 673. Found: m/z 696
[MϩNa]ϩ.
Octyl 2-O-Benzyl-4,6-O-benzylidene-b-D-mannopyranosyl-(1→4)-2,3,6-
tri-O-benzyl-b-D-glucopyranoside (14) To a solution of 13 (180 mg, 0.15
mmol) in THF (3 ml) was added tetrabutylammoniumfluoride, 1.0 M solution
3,4-Di-O-benzyl-6-O-pivaloyl-2-deoxy-2-phthalimido-b-D-glucopyra- in THF (TBAF: 4 ml). The reaction mixture was stirred for 2 h at room tem-
nosyl Trichloroacetimidate (10) To a solution of 9 (26 mg, 0.04 mmol) in perature, then extracted with CHCl3, washed with 5% HCl, dried (Na2SO4)