1258
T. Schulz, T. Eicher
PAPER
13C NMR (CDCl3): = 169.9, 169.4, 168.0, 165.4, 161.6, 160.8,
135.0, 131.9, 128.6, 128.6, 128.5, 128.2, 123.1, 114.3, 92.9, 70.2,
70.6, 69.8, 68.2, 67.2, 65.8, 61.9, 20.6, 20.5, 20.4.
residue purified by flash chromatography (SiO2, Et2O–petroleum
ether, 1:1) to give the product.
Yield: 124 mg (46%); colorless oil.
1H NMR (CDCl3): = 8.07 (d, 2 H, J = 8.8 Hz, ArH), 6.96 (d, 2 H,
J = 8.8 Hz, ArH), 5.45 (t, 1 H, J = 8.8 Hz, glucose H4), 5.11 (dd, 1
H, J1 = 8.8, J2 = 5.8 Hz, glucose H3), 4.86 (dd, 1 H, J1 = 11.1,
J2 = 6.2 Hz, glucose H2), 4.82 (d, 2 H, J = 8.4 Hz, ArOCH2CO2R),
4.80 (dd, 1 H, J1 = 11.7, J2 = 3.1 Hz, glucose H6), 4.48 (d, 1 H,
J = 5.3 Hz, anomeric CH), 4.21 (dd, 1 H, J1 = 11.7, J2 = 5.3 Hz, glu-
cose H6), 4.10–4.03 (m, 2 H), 3.99–3.95 (m, 1 H, glucose H5),
3.19–3.13 (m, 1 H), 3.07–3.02 (m, 1 H), 2.08 (s, 3 H), 2.04 (s, 3 H),
2.03 (s, 3 H), 1.17–0.95 (m, 4 H).
Glycosylation of Monobenzylated Butane-1,4-diol (8a) with
Trichloroacetimidate 16
A solution of trichloroacetimidate 16 (3.52 g, 4.90 mmol) and 4-
benzyloxy-1-butanol (8a) (973 mg, 5.40 mmol) in anhyd CH2Cl2
(20 mL) was cooled in a salt H2O bath to approximately –20 °C.
Within 15 min a solution of trimethylsilyl trifluoromethane-
sulfonate (0.1 M; 500 l, 0.50 mmol) in CH2Cl2 was added. After stir-
ring for 1 h at –20 °C the reaction was quenched by the addition of
a few drops of Et3N. CH2Cl2 (100 mL) was added and the solution
was washed with sat. aq K2CO3 (2 × 50 mL). The combined organic
phases were dried (MgSO4) and concentrated to give a crude prod-
uct, which was purified by flash column chromatography (SiO2,
Et2O–petroleum ether, 1:1) to give the pure product.
13C NMR (CDCl3): = 170.0, 169.4, 169.2, 168.6, 165.9, 161.9,
132.0, 123.5, 114.9, 99.3, 73.6, 72.7, 70.8, 69.2, 69.0, 65.9, 64.9,
61.6, 26.3, 25.4, 20.7.
MS (CI): m/z (%) = 539 (22, M+).
Yield: 3.24 g (87%); slightly yellow oil.
Anal. Calcd for C25H30O13 (538.50): C, 55.76; H, 5.62. Found C,
55.69; H, 5.58.
1H NMR (CDCl3): = 7.97 (d, 2 H, J = 8.1 Hz, ArH), 7.40–7.27 (m,
10 H, benzyl H), 6.93 (d, 2 H, J = 8.1 Hz, ArH), 5.47 (dd, 1 H,
J1 = J2 = 8.4 Hz, glucose H), 5.22 (s, 2 H, PhCH2), 5.10 (m 1 H, glu-
cose H), 4.85 (dd, 1 H, J1 = 8.4, J2 = 5.9 Hz, glucose H), 4.76 (2 H,
ArOCH2CO2Bn), 4.51–4.47 (m, 1 H, glucose H6), 4.48 (d, 1 H,
J = 7.1 Hz, anomeric CH), 4.45 (s, 2 H, PhCH2), 4.40–4.34 (m, 2 H,
glucose H5, H6), 3.38 (t, 2 H, J = 6.5 Hz, OCH2R), 3.15 (t, 2 H,
J = 6.4 Hz, OCH2R), 2.04 (s, 3 H), 2.03 (s, 3 H), 2.02 (s, 3 H), 1.14–
0.98 (m, 4 H).
13C NMR (CDCl3): = 170.0, 169.5, 169.2, 168.5, 165.8, 161.9,
134.2, 134.1, 132.0, 128.3, 128.3, 127.7, 127.6, 127.5, 127.4, 123.4,
114.9, 99.2, 72.9, 72.8, 72.4, 70.8, 69.3, 69.2, 69.0, 67.2, 65.9, 65.7,
26.4, 25.3, 20.7, 20.5, 20.4.
Cyclization of Hydroxy Acid 18 According to the Modified DCC
Protocol
To a refluxing solution of DCC (206 mg, 1.00 mmol), DMAP (183
mg, 1.50 mmol) and DMAP trifluoroacetate (236 mg, 1.00 mmol)
in anhyd, EtOH-free CHCl3 (50 mL) was added a solution of hy-
droxy acid 18 (278 mg, 0.50 mmol) in anhyd, EtOH-free CHCl3 (50
mL) within 4 h. After complete addition, the resulting solution was
refluxed for 16 h. After cooling to r.t., MeOH (2 mL) and HOAc
(0.1 mL) were added and stirring was continued for 30 min at r.t.
The precipitated N,N -dicyclohexyl urea was filtered off and
washed with portions of anhyd CHCl3 (2 × 25 mL) . The filtrate was
concentrated and the crude product obtained was purified by flash
chromatography (silica gel; Et2O–petroleum ether, 1:1) to give the
product.
MS (CI): m/z (%) = 737 (7, M+).
Anal. Calcd for C39H44O14 (736.76): C, 63.58; H, 6.02. Found C,
63.62; H, 6.05.
Yield: 145 mg (54%); colorless oil.
The spectral data obtained for the product matched those of the
product from the previous experiment.
Debenzylation of Glycoside 17
A solution of glycoside 17 (3.00 g, 4.07 mmol) and Pearlman’s cat-
alyst (0.60 g) in THF–MeOH (1:1; 200 mL) was hydrogenated in a
Parr hydrogenation apparatus under a pressure of 35 psi for 18 h.
The catalyst was filtered off and the resulting solution was concen-
trated. The crude product was purified by passing through a short
plug of silica gel eluting with Et2O to give the pure compound.
Hydrogenolysis of Benzyl Ester 15
Benzyl ester 15 (1.85 g, 3.00 mmol) was dissolved in THF (200
mL), 5% palladium on charcoal (0.40 g) was added and the resultant
mixture was hydrogenated at 35 psi for 4 h. The catalyst was filtered
off, the solvent evaporated and the residue purified by filtration
through a short plug of silica gel eluting with Et2O to give the prod-
uct.
Yield: 1.63 g (72%); colorless oil.
1H NMR (CDCl3): = 8.06 (d, 2 H, J = 7.9 Hz, ArH), 7.02 (d, 2 H,
J = 7.9 Hz, ArH), 5.52 (dd, 1 H, J1 = J2 = 8.6 Hz, glucose H), 5.19
(m 1 H, glucose H), 4.80 (dd, 1 H, J1 = 8.2, J2 = 5.3 Hz, glucose H),
4.73 (2 H, ArOCH2CO2H), 4.49–4.43 (m, 2 H, glucose H6 + ano-
meric CH), 4.39–4.31 (m, 2 H, glucose H5, H6), 3.35 (t, 2 H, J = 6.7
Hz, OCH2R), 3.20 (t, 2 H, J = 6.3 Hz, OCH2R), 2.04 (s, 3 H), 2.03
(s, 3 H), 2.02 (s, 3 H), 1.19–1.01 (m, 4 H).
13C NMR (CDCl3): = 169.4, 169.3, 169.2, 168.9, 165.7, 162.0,
132.3, 124.1, 114.7, 99.5, 71.9, 71.0, 69.4, 69.3, 69.1, 68.6, 66.8,
65.7, 27.5, 25.9, 21.0, 20.8, 20.4.
Yield: 1.38 g (87%); slightly yellow oil.
1H NMR (CDCl3): = 8.01 (d, 2 H, J = 8.8 Hz, ArH), 7.54 (br s, 1
H, OH), 6.95 (d, 2 H, J = 8.8 Hz, ArH), 5.76 (d, 1 H, J = 8.0 Hz,
anomeric CH), 5.29 (t, 1 H, J = 9.3 Hz, glucose H), 5.22 (t, 1 H,
J = 9.3 Hz, glucose H), 5.15 (t, 1 H, J = 8.4 Hz, glucose H), 4.72 (s,
2 H, ArOCH2CO2H), 4.48 (dd, 1 H, J1 = 12.4, J2 = 2.2 Hz, glucose
H6), 4.35 (dd, 1 H, J1 = 12.4, J2 = 4.4 Hz, glucose H6), 3.99–3.95
(m, 1 H, glucose H5), 2.09 (s, 3 H), 2.04 (s, 3 H), 2.02 (s, 3 H), 2.01
(s, 3 H).
MS (CI): m/z (%) = 558 (2, M+ + 1).
13C NMR (CDCl3): = 171.8, 170.2, 169.5, 169.4, 169.0, 165.6,
161.5, 132.0, 114.4, 112.0, 91.8, 73.0, 72.8, 70.5, 68.3, 64.7, 62.1,
24.9, 20.5.
Cyclization of Hydroxy Acid 18 According to the Yamaguchi
Protocol
MS (CI): m/z (%) = 467 (23, M+ – HOAc).
To a solution of hydroxy acid 18 (278 mg, 0.50 mmol) in anhyd
THF (5 mL) was added anhyd Et3N (56 mg, 0.55 mmol, 77 l) fol-
lowed by 2,6-dichlorobenzoyl chloride (105 mg, 0.50 mmol). After
2 h at r.t., the suspension was diluted with anhyd toluene (100 mL).
DMAP (37 mg, 3.00 mmol) was added and the milky white suspen-
sion was stirred for 18 h at r.t. The solvent was evaporated and the
Esterification of Carboxylic Acid 19 with Butane-1,4-diol (8b)
A solution of acid 19 (1.32 g, 2.50 mmol), butane-1,4-diol (1.13 g,
12.5 mmol), 2-chloro-1-methylpyridinium iodide (960 mg, 3.76
mmol) and anhyd Et3N (760 mg, 7.52 mmol, 1.05 mL) in anhyd
MeCN (50 mL) was refluxed for 3 h. The solvent was evaporated
Synthesis 2003, No. 8, 1253–1261 ISSN 1234-567-89 © Thieme Stuttgart · New York