were added and the mixture was stirred for 4 h at 0 °C. After
concentration, the residue was purified by flash chromatography
on silica gel (petroleum ether: EtOAc, 12:1) to give compound 8
4.2.7 2´-O-[N-[3,4,6-tri(O-allyloxycarbonyl)-2-fluoroallylester-
β-D-glucopyranosyl]carbamoyl-4-
oxy]benzyloxycarbonylpaclitaxel (10)
(510 mg, 64%) as a syrup. R
f
= 0.75 (petroleum ether: EtOAc,
;
3:1); [α]20D -3.9 (c 0.12, CHCl3)
1H NMR (400 MHz, CDCl3)
Compound 2 (55 mg, 0.073 mmol) and paclitaxel (63 mg,
0.073 mmol) were dissolved in distilled CH2Cl2 (5 mL). Then 4-
dimethylaminopyridine (DMAP) was added under argon and the
mixture was stirred for 12 h at room temperature. After
evaporation, purification over silica gel afforded the compound
δ 7.26 (d, J = 7.9 Hz, 2H, ArH), 7.19 (s, 1H, ArH), 7.18 (d, J
= 1.5 Hz, 1H, ArH), 6.87 (s, 1H, NH), 5.89–5.81 (m, 2H, 2×
CHCH2), 5.79 (d, J = 5.0 Hz, 1H, 2F-Glc1-H), 5.79–5.75 (m,
1H, CHCH2), 5.32
(t, J = 9.7 Hz, 1H, 2F-Glc2-H), 4.60 (s, 2H, ArCH2), 4.59
4.50 (m, 6H, 3× CHCH2), 4.42 4.19 (m, 3H, 2F-Glc4,5,6b-
H), 3.89 (d, J = 10.0 Hz, 1H, 2F-Glc6a-H), 0.84 (s, 9H,
C(CH3)3), -0.01 (s, 6H, Si(CH3)2). 13C NMR (101 MHz,
CDCl3) δ 154.49, 154.01, 153.70, 131.27, 130.96, 126.87,
119.01, 92.40 (2F-Glc1-C), 91.90 (2F-Glc1-C),, 88.88, 86.97,
76.45, 71.91, 71.50, 71.43, 69.29, 69.15, 68.85, 64.74, 64.49,
25.90, 18.36, -5.27. 19F NMR (376 MHz, CDCl3) δ -199.53, -
200.28. HRMS m/z calcd for C32H44FNO13SiNa [M+Na]+:
720.2464, found: 720.2417.
–5.13 (m, 7H, 3×CH2CH+2F-Glc3-H), 4.91
–
10 (65 mg, 60%) as a white solid. R =0.48 (petroleum ether:
f
EtOAc, 1:1); [α]20 -56.5 (c 0.16, CHCl3); 1H NMR (400
–
D
MHz, CDCl3) δ 8.05 (d, J = 7.6 Hz, 2H), 7.63 (d, J = 7.6 Hz,
2H), 7.52 (t, J = 7.2 Hz, 1H), 7.46
(m, 11H), 6.92 (s, 1H), 6.26 6.16 (m, 2H), 5.93
5.61 (d, J = 7.0 Hz, 1H, 2F-Glc1-H), 5.37 (d, J = 2.8 Hz, 1H),
5.33 5.12 (m, 7H), 5.02 (dd, J = 23.2, 12.0 Hz, 2H), 4.94
4.85 (m, 2H), 4.62 4.47 (m, 6H), 4.41 4.00 (m, 6H), 3.87 (td,
J = 9.6, 3.2 Hz, 1H), 3.74 (d, J = 7.2 Hz, 1H), 2.48 (s, 2H),
2.40 2.28 (m, 4H), 2.19 2.09 (m, 4H), 1.87 1.74 (m, 5H),
1.62 (s, 3H), 1.24
1.12 (m, 6H), 1.06 (s, 3H). 13C NMR (101
–7.37 (m, 3H), 7.34–7.17
–
–
5.73 (m, 5H),
–
–
–
–
–
–
–
–
4.2.5 N-[4-(hydroxymethyl)phenyl]-O-[3,4,6-tri-(O-
allyloxycarbonyl)-2-fluoroallylester-β-D-
glucopyranosyl]carbamate (9)
MHz, CDCl3) δ 203.72, 171.19, 169.80, 167.88, 167.16,
166.96, 154.44, 154.05, 153.99, 153.66, 142.48, 137.50,
136.62, 133.63, 133.43, 132.82, 131.95, 131.23, 130.97,
130.87, 130.17, 129.96, 129.59, 129.13, 129.06, 128.69,
128.61, 128.49, 127.10, 126.56, 119.32, 119.14, 119.01, 92.20
(2F-Glc1-C), 91.96 (2F-Glc1-C), 88.84, 86.92, 84.40, 81.01,
79.05, 77.32, 77.00, 76.83, 76.68, 76.37, 75.54, 75.04, 72.09,
72.05, 71.96, 71.40, 71.32, 70.25, 69.29, 69.14, 68.83, 64.67,
58.43, 52.75, 45.60, 43.13, 35.55, 29.63, 26.75, 22.64, 22.04,
20.76, 14.71, 9.57. 19F NMR (376 MHz, CDCl3) δ -200.23.
HRMS m/z calcd for C74H79FN2O28Na [M+Na]+: 1485.4701,
found: 1485.4572.
To a solution of compound 8 (340 mg, 0.78 mmol) in
anhydrous THF (5 mL), glacial acetic acid (38 µL, 0.63 mmol)
and TBAF (174 µL, 0.63 mmol) were added. After stirring
overnight at room temperature, the mixture was diluted with
dichloromethane, washed with brine, dried over Na2SO4 and
concentrated under reduce pressure. Chromatography afforded 9
(190 mg, 67%). R
-6.2 (c 0.10, CHCl3)
1H), 7.28 (d, J = 7.6 Hz, 2H), 7.19 (d, J = 8.4 Hz, 2H), 5.90
5.71 (m, 4H), 5.33 5.10 (m, 7H), 4.92 4.83 (t, J = 19.6 Hz,
9.6 Hz, 1H), 4.63 4.14 (m, 12H), 3.84 (dt, J = 10.0 Hz, 2.8
f
= 0.42 (petroleum ether: EtOAc, 1:1); [α]20
;
D
1H NMR (400 MHz, CDCl3) δ 7.39 (s,
–
–
–
4.2.8 2´-O-[N-(2-fluoroallylester-β-D-
glucopyranosyl)carbamoyl-4-oxy]benzyloxycarbonylpaclitaxel
(1)
–
Hz,1H). 13C NMR (101 MHz, CDCl3) δ 154.43, 153.99,
153.67, 131.19, 130.98, 130.88, 127.78, 119.28, 119.07,
119.01, 92.08 (2F-Glc1-C), 91.84 (2F-Glc1-C), 88.75, 86.84,
76.50, 76.40, 71.71, 71.39, 71.32, 69.25, 69.21, 69.11, 68.84,
64.67, 64.49. 19F NMR (376 MHz, CDCl3) δ -200.39. HRMS
m/z calcd for C26H30FNO13Na [M+Na]+: 606.1599, found:
606.1587.
To a solution of compound 10 (60 mg, 0.04 mmol) in
anhydrous THF (6 mL), triethylamine (17 µL, 0.12 mmol) and
HCOOH (3 µL, 0.082 mmol) were added. The mixture was
stirred for 10 min under argon, then Pd(PPh3)4 (9.5 mg, 0.008
mmol) was added at 0 °C and stirred for 2 h at room temperature.
After concentration, the product was purified over silica gel
(DCM: MeOH, 10:1) to give target 1 (36 mg, 72%) as white
4.2.6 O-[[N-[3,4,6-tri (O-allyloxycarbonyl)-2-fluoroallylester-β-
D-glucopyranosyl]carbamoyl-4-oxy]benzyloxycarbonyl]-4-
solid. R
=0.42 (DCM: MeOH, 10:1); [α]20D -31.8 (c 1.0, CHCl3);
f
nitrophenol (2)
1H NMR (400 MHz, CDCl3) δ 8.10 (d, J = 7.6 Hz, 2H), 7.70
(d, J = 8.0 Hz, 2H), 7.63 – 7.29 (m, 14H), 7.25 (s, 2H), 6.27
(s, 1H), 6.16 (s, 1H), 5.94 (d, J = 6.4 Hz, 1H), 5.72 (s, 1H),
5.65 (d, J = 6.8 Hz, 1H, 2F-Glc1-H), 5.44 (s, 1H), 5.09 (s,
1H), 4.95 (d, J = 9.2 Hz, 2H), 4.36 (s, 1H), 4.27 (s, 1H), 4.17
(s, 1H), 3.92 – 3.64 (m, 2H), 3.49 (d, J = 5.0 Hz, 8H), 2.39 (s,
2H), 2.18 (s, 3H), 1.76 (s, 1H), 1.64 (s, 11H), 1.25 (s, 1H),
1.18 (s, 3H), 1.11 (s, 2H), 0.96 (d, J = 5.4 Hz, 2H). 13C NMR
(101 MHz, CDCl3) δ 203.89, 171.28, 169.88, 168.04, 167.52,
166.82, 154.00, 151.94, 141.98, 139.24, 136.61, 135.12,
133.40, 132.79, 130.11, 129.08, 128.53, 127.14, 126.80,
123.96, 123.42, 119.07, 115.82, 114.02, 92.20 (2F-Glc1-C),
92.01 (2F-Glc1-C), 88.35, 86.90, 84.42, 80.86, 78.78, 77.20,
60.35, 58.23, 53.39, 43.07, 34.68, 33.77, 31.88, 31.58, 31.39,
30.25, 30.15, 29.65, 29.61, 29.46, 29.31, 29.11, 28.90, 26.58,
22.64, 22.51, 21.83, 20.73, 14.55, 14.14, 14.07, 9.70. 19F NMR
Anhydrous pyridine (36 µL, 0.45 mmol) was added to a
solution of compound 9 (130 mg, 0.22 mmol) in anhydrous
CH2Cl2 (5 mL). Then, 4-nitrophenyl chloroformate (90 mg, 0.45
mmol) was added and the mixture was stirred for 2 h at 0 °C.
After evaporation, the residue was chromatographed over silica
gel (petroleum ether: EtOAc, 3:1) to give compound 2 (136 mg,
78%). R
f
=0.35 (petroleum ether: EtOAc, 3:1); [α]20 -16.1 (c
D
0.43, CHCl3); 1H NMR (400 MHz, CDCl3) δ 8.23
–
8.15 (d, J =
9.2, 2H), 7.40
8.8, 4.4 Hz, 4H), 5.34 – 5.11 (m, 9H), 4.90 (t, J = 19.6 Hz, 9.6
Hz, 1H), 4.63 4.51 (m, 6H), 4.42 4.19 (m, 3H), 3.90 (dt, J =
–7.27 (m, 6H), 6.99 (s, 1H), 5.84 (ddt, J = 14.6,
–
–
10.0 Hz, 3.2 Hz,1H). 13C NMR (101 MHz, CDCl3) δ 155.45,
154.47, 153.99, 153.69, 152.41, 150.38, 145.37, 145.31,
137.60, 131.24, 130.97, 130.88, 129.86, 125.26, 121.74,
119.37, 119.19, 119.08, 92.23 (2F-Glc1-C), 91.99 (2F-Glc1-
C), 88.88, 86.96, 76.56, 76.36, 71.98, 71.41, 71.35, 70.47,
69.33, 69.19, 68.89, 64.72. 19F NMR (376 MHz, CDCl3) δ -
200.26. HRMS m/z calcd for C33H33FN2O17Na [M+Na]+:
771.1661, found: 771.1645.
(376 MHz, CDCl3)
δ -199.54. HRMS m/z calcd for
C62H67FN2O22Na [M+Na]+: 1233.4067, found: 1233.4074.
4.2.9 1,2,3,4,6-penta-(O-Allyloxycarbonyl-D-glucopyranose
(11).