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A. Nikolakakis et al. / Bioorg. Med. Chem. 11 (2003) 1551–1556
.
solution of BF3 OEt2 (4 mL, 0.032 mmol) in CH2Cl2
(40 mL) was added and the mixture was stirred at 4 ꢁC
for 1 h. The mixture was separated from the molecular
sieves. After dilution with chloroform, the mixture was
washed with aqueous NaHCO3 to pH 8 and then with
brine to neutrality. The organic phase was dried, filtered
and evaporated. The residue was purified by chromato-
graphy on silica gel (gradient of EtOAc/hexane, 30:70 to
40:60) affording compound 11 (0.065 g, 43% based on
J=11.3 Hz, 1H, Bn-3b), 4.61 (d, J=12.4 Hz, 1H, Bn-
6a), 4.56 (d, J=11.2 Hz, 1H, Bn-4b), 4.53 (d,
J=12.4 Hz, 1H, Bn-6b), 4.39 (d, J=11.4 Hz, 1H, OH-
9), 4.34 (dd, J=9.7, 7.6 Hz, 1H, H-7), 4.30 (o.m, 1H, H-
9), 4.30 (o.d, 1H, H-20a), 4.16 (o.d, J=8.5 Hz, 1H, H-
20b), 3.85 (t, J=8.6 Hz, 1H, GL-H-3), 3.73 (o.m, 2H,
GL-H-6), 3.70 (o.t, J=9.0 Hz, 1H, GL-H-4), 3.59 (d.t,
J=10.0, 3.0 Hz, 1H, GL-H-5), 3.45 (t, J=8.1 Hz, 1H,
GL-H-2), 3.12 (d, J=6.0 Hz, 1H, H-3), 2.76 (ddd,
J=15.5, 9.0, 7.8 Hz, 1H, H-6a), 2.26 (o.m, 1H, H-14a),
2.23 (s, 3H, Ac), 2.08 (br.s, 3H, H-18), 2.07 (o.m, 1H,
H-14b), 2.07 (o.m, 1H, H-6b), 1.99 (s, 3H, Ac), 1.84 (s,
3H, H-19), 1.65 (s, 3H, H-17), 1.64 (s, 1H, OH-1), 1.09
(s, 3H, H-16); 13C NMR (125 MHz, CDCl3) d 171.5
(CO-Ac), 169.9 (CO-Ac), 166.9 (CO-Bz), 141.1(C-12),
138.0 (C-1 of Ph(Bn)), 135.3 (C-11), 133.5 (C-4 of Bz),
130.0 (C-2,6 of Bz), 128.5 (C-3,5 of Bz), 128.2 (C-2,6 of
Ph(Bn)), 127.2 (C-4 of Ph(Bn)), 102.1 (GL-1), 84.7 (GL-
3), 84.4 (C-5), 82.3 (C-7), 82.1 (C-4), 80.3 (GL-2), 78.6
(C-1), 77.9 (GL-4), 76.3 (C-20), 75.8 (C-9), 75.1 (GL-5),
74.8 (Bn-3), 74.5 (Bn-4), 74.1 (Bn-2), 73.2 (Bn-6), 73.0
(C-2), 72.5 (C-10), 68.5 (C-13), 68.5 (GL-6), 47.4 (C-3),
45.4 (C-8), 42.6 (C-15), 38.6 (C-14), 37.2 (C-6), 28.2 (C-
16), 22.9 (Ac), 21.1 (Ac), 22.0 (C-17), 14.9 (C-18), 13.0
(C-19); FAB-HR-MS m/z: 1243.4033 (calculated for
C65H74O16Cs, 1243.4031).
1
recovered 2). H NMR of 11 (500 MHz, CDCl3) d 8.08
(d, J=7.7 Hz, 2H, H-2,6 of Bz), 7.59 (t, J=7.5 Hz, 1H,
H-4 of Bz), 7.46 (t, J=7.7 Hz, 2H, H-3,5 of Bz), 7.33–
7.14 (m, 20H, Ph(Bn)), 6.15 (o.d, J=11.0 Hz, 1H, H-
10), 6.14 (o.m, 1H, H-13), 5.74 (d, J=6.0 Hz, 1H, H-2),
4.91 (o.d, J=10.0 Hz, 1H, H-5), 4.88 (d, J=11.9 Hz,
1H, Bn-2a), 4.87 (o.d, J=7.0 Hz, 1H, GL-H-1), 4.78
(o.d, 1H, Bn-2b), 4.75 (o.d, J=11.2 Hz, 2H, Bn-3a/b),
4.75 (o.d, 1H, Bn-4a), 4.61 (d, J=12.2 Hz, 1H, Bn-6a),
4.56 (o.d, J=11.2 Hz, 1H, Bn-4b), 4.54 (o.d,
J=12.2 Hz, 1H, Bn-6b), 4.44 (d, J=11.4 Hz, 1H, OH-
9), 4.34 (o.dd, J=9.5, 7.7 Hz, 1H, H-7), 4.31 (o.m, 1H,
H-9), 4.29 (o.d, J=8.5 Hz, 1H, H-20a), 4.15 (d,
J=8.3 Hz, 1H, H-20b), 3.84 (t, J=8.5 Hz, 1H, GL-H-
3), 3.73 (o.m, 2H, GL-H-6), 3.70 (o.t, J=9.0 Hz, 1H,
GL-H-4), 3.60 (d.t, J=9.8, 2.8 Hz, 1H, GL-H-5), 3.46
(t, J=7.6 Hz, 1H, GL-H-2), 3.07 (d, J=5.8 Hz, 1H, H-
3), 2.79 (ddd, J=15.5, 9.0, 7.5 Hz, 1H, H-6a), 2.23 (s,
3H, Ac), 2.18 (d, J=8.5 Hz, 1H, H-14a), 2.15 (s, 3H,
Ac), 2.08 (dd, J=15.4, 10.1 Hz, 1H, H-6b), 1.98 (s, 3H,
Ac), 1.93 (s, 3H, H-18), 1.85 (s, 3H, H-19), 1.69 (s, 3H,
H-17), 1.67 (s, 1H, OH-1), 1.24 (s, 3H, H-16); 13C NMR
(125 MHz, CDCl3) d 170.2 (CO-Ac), 169.8 (CO-Ac),
168.8 (CO-Ac), 166.8 (CO-Bz), 138.0 (C-12), 138.0 (C-1
of Ph(Bn)), 135.7 (C-11), 133.6 (C-4 of Bz), 130.0 (C-2,6
of Bz), 128.5 (C-3,5 of Bz), 128.2 (C-2,6 of Ph(Bn)),
127.2 (C-4 of Ph(Bn)), 102.2 (GL-1), 84.7 (GL-3), 84.2
(C-5), 82.7 (C-7), 81.7 (C-4), 80.1 (GL-2), 78.6 (C-1),
77.9 (GL-4), 76.3 (C-20), 75.5 (C-9), 75.1 (GL-5), 74.9
(Bn-3), 74.6 (Bn-4), 74.1 (Bn-2), 73.3 (Bn-6), 73.3 (C-2),
72.0 (C-10), 69.6 (C-13), 68.6 (GL-6), 47.5 (C-3), 45.4
(C-8), 42.8 (C-15), 37.2 (C-6), 35.2 (C-14), 28.2 (C-16),
22.8 (Ac), 22.4 (C-17), 21.2 (Ac), 21.1 (Ac), 14.7 (C-18),
13.1 (C-19); FAB-HR-MS m/z: 1285.4141 (calculated
for C67H76O17Cs, 1285.4137).
7-(20,30,40,60-Tetra-O-benzyl-ꢀ-D-glucopyranosyloxy)-9-
dihydrobaccatin III-13-(4S,5R)-N-(t-butyloxycarbonyl)-2
- (4 - methoxyphenyl) - 4 - phenyl - 5 - oxazolidinecarboxylic
acid ester 14. Glucoside 12 (0.037 g, 0.033 mmol) in tol-
uene (0.6 mL) was treated with (4S,5R)-N-(t-butyloxy-
carbonyl)-2-(4-methoxyphenyl)-4-phenyl-5-oxazolidine-
carboxylic acid (13), (0.025 g, 0.063 mmol) in 0.3 mL
CH2Cl2, 4-pyrrolidinopyridine (3 mg, 0.020 mmol) and
DCC (0.014 g, 0.068 mmol) at 75 ꢁC for 3.5 h. The reac-
tion mixture was diluted with ethyl acetate, washed with
5% NaHSO4 to pH 1, 5% NaHCO3 to pH 8 and then
with brine to neutrality. The organic layer was dried,
filtered and evaporated. The residue was purified by
flash chromatography on silica gel with EtOAc/hexane,
40:60 as eluent to give a mixture of diastereomers 14
1
(0.046 g, 93%). H NMR of 14 (500 MHz, CDCl3) d
8.06 (d, J=7.5 Hz, 2H, H-2,6 of Bz), 7.61 (t, J=7.5 Hz,
1H, H-4 of Bz), 7.47 (t, J=7.8 Hz, 2H, H-3,5 of Bz),
7.38 (o.m, 2H, H-2,6 of p-(OMe)Ph), 7.33–7.14 (m, 20H,
Ph(Bn)), 6.88 (d, J=8.8 Hz, 2H, H-3,5 of p-(OMe)Ph),
6.36 (v.br, 1H, H-50), 6.06 (d, J=11.3 Hz, 1H, H-10),
6.00 (br, 1H, H-13), 5.68 (d, J=6.0 Hz, 1H, H-2), 5.40
(br, 1H, H-30), 4.86 (o.d, 1H, Bn-2a), 4.81 (br.d, 1H,
GL-H-1), 4.77 (o.m, 1H, H-5), 4.77 (o.d, 1H, Bn-3a),
4.76 (o.d, 1H, Bn-2b), 4.75 (o.d, 1H, Bn-4a), 4.72 (o.d,
1H, Bn-3b), 4.60 (o.d, 1H, Bn-6a), 4.56 (o.d, 1H, Bn-
4b), 4.55 (o.m, 1H, H-20), 4.51 (o.d, 1H, Bn-6b), 4.42 (d,
J=11.3 Hz, 1H, OH-9), 4.26 (o.m, 1H, H-7), 4.26 (o.m,
1H, H-9), 4.20 (d, J=8.5 Hz, 1H, H-20a), 4.08 (d,
J=8.5 Hz, 1H, H-20b), 3.81 (o.m, 1H, GL-H-3), 3.75
(o.m, 2H, GL-H-6), 3.75 (o.br.s, 3H, CH3 of p-
(OMe)Ph), 3.72 (o.m, 1H, GL-H-4), 3.56 (br.d,
J=9.7 Hz, 1H, GL-H-5), 3.43 (t, J=8.0 Hz, 1H, GL-H-
2), 2.95 (d, J=6.0 Hz, 1H, H-3), 2.71 (m, 1H, H-6a),
2.17 (o.m, 1H, H-14a), 2.03 (o.m, 1H, H-14b), 2.02
(o.m, 1H, H-6b), 1.96 (s, 3H, Ac), 1.79 (s, 3H, H-19),
7-(20,30,40,60-Tetra-O-benzyl-ꢀ-D-glucopyranosyloxy)-9-
dihydrobaccatin III 12. A solution of glucoside 11
(0.065 g, 0.056 mmol) in THF/0.05 M KPO4, pH 7.0
buffer (2.1 mL/1.05 mL) was treated with NaBH4 (3 ꢃ
8.6 mg, 0.23 mmol) at 23 ꢁC over a period of 6 h and at
4 ꢁC for 18 h. The reaction was quenched with acetone
and brine. The mixture was extracted with EtOAc and
the combined organic layers were dried, filtered and
evaporated. The residue was purified by chromato-
graphy on silica gel (EtOAc/hexane, 40:60) affording
compound 12 (0.040 g, 64%). 1H NMR of 12 (500 MHz,
CDCl3) d 8.10 (d, J=7.9 Hz, 2H, H-2,6 of Bz), 7.61 (t,
J=7.3 Hz, 1H, H-4 of Bz), 7.59 (t, J=7.7 Hz, 2H, H-3,5
of Bz), 7.33–7.14 (m, 20H, Ph(Bn)), 6.12 (d, J=11.1 Hz,
1H, H-10), 5.72 (d, J=6.0 Hz, 1H, H-2), 4.89 (o.d, 1H,
Bn-2a), 4.88 (o.d, 1H, H-5), 4.89 (o.d, 1H, GL-H-1),
4.80 (o.d, 1H, Bn-3a), 4.78 (o.d, 1H, Bn-4a), 4.78 (o.m,
1H, H-13), 4.78 (o.d, J=11.4 Hz, 1H, Bn-2b), 4.74 (d,