Greenwald et al.
SCHEME 2
45.6, 43.1, 35.5, 26.8, 22.7, 22.1, 20.8, 14.8, 9.6; ESI-MS (ES+)
(m/z) calcd for C64H65N2O17 1133.00, found 1133.46 (MH+).
P a clita xel Bsm oc Der iva tive: Com p ou n d 6. To a solu-
tion of 1 (1.00 g, 1.17 mmol), 5 (0.375 g, 1.34 mmol), and
(dimethylamino)pyridine (DMAP, 0.043 g, 0.35 mmol) in
methylene chloride (DCM, 100 mL) cooled to 10 °C was added
EDC (0.336 g, 1.75 mmol) and the solution was continuously
stirred at 10 °C for 50 min before it was warmed to room
temperature and stirred for another 30 min. The reaction
mixture was washed with 0.1 M HCl (2 × 50 mL) and water
(50 mL), dried (MgSO4), and filtered, and solvent was evapo-
rated under reduced pressure to give 6 (1.20 g, 1.05 mmol,
90%). 1H NMR (300.07 MHz, CDCl3) δ 1.14 (s, 3H), 1.22 (s,
3H), 1.68 (s, 3H), 1.83 (s, 2H), 1.90 (s, 3H), 2.22 (s, 3H), 2.30
(s, 1H), 2.43 (s, 3H), 2.56 (s, H), 3.79 (d, J ) 6.3 Hz, H), 4.04
(m, H), 4.12 (d, J ) 5.7 Hz, H), 4.19 (d, J ) 8.1 Hz, H), 4.30 (d,
J ) 8.4 Hz, H), 4.42 (m, H), 4.96 (d, J ) 9.6 Hz, H), 5.06 (s,
H), 5.56 (m, H), 5.66 (d, J ) 4.2 Hz, H), 6.00 (m, H), 6.22 (t, J
) 8.4 Hz, H), 6.29 (s, H), 7.08 (s, H), 7.15 (d, J ) 8.7 Hz, H),
7.30-7.70 (m, 16H), 7.77 (d, J ) 8.4 Hz, H), 8.13 (d, J ) 7.5
Hz, H); 13C NMR (67.8 MHz, CDCl3) δ 203.5, 171.0, 169.7,
168.7, 167.5, 167.0, 166.8, 155.3, 142.3, 138.8, 136.8, 136.5,
133.6, 133.6, 132.7, 131.9, 130.5, 129.8, 129.0, 128.5, 127.1,
126.8, 126.6, 125.3, 121.4, 84.4, 81.1, 79.1, 76.4, 75.6, 75.0, 74.9,
72.0, 58.5, 57.2, 52.9, 45.7, 43.2, 42.8, 35.6, 26.8, 22.7, 20.9,
14.9, 9.7; ESI-MS (ES+) (m/z) calcd for C59H61N2O19S 1132.94,
found 1133.42 (MH+).
was repeated twice and the final residue was dried in a
desiccator over phosphorus pentoxide to give 4 (0.791 g, 0.862
mmol, 94%). 1H NMR (300.07 MHz, CDCl3) δ 1.14 (s, 3H), 1.23
(s, 3H), 1.68 (s, 3H), 1.95 (s, 3H), 2.22 (s, 3H), 2.46 (s, 3H),
2.58 (s, H), 3.82 (d, J ) 6.6 Hz, H), 4.20 (d, J ) 8.7 Hz, H),
4.31 (d, J ) 8.4 Hz, H), 4.47 (m, H), 4.97 (d, J ) 9.3 Hz, H),
5.55 (d, J ) 3.3 Hz, H), 5.68 (d, J ) 6.9 Hz, H), 6.00 (d, J )
3.3 Hz, H), 6.25 (t, J ) 8.4 Hz, H), 6.30 (s, H), 6.96 (s, H), 6.99
(d, J ) 8.7 Hz, H), 7.30-7.70 (m, 16H), 7.73 (d, J ) 4.2 Hz,
H), 8.13 (d, J ) 6.9 Hz, H); 13C NMR (67.8 MHz, CDCl3) δ
203.5, 173.2, 171.0, 169.6, 167.8, 166.9, 166.8, 142.4, 136.7,
133.6, 133.5, 132.8, 131.9, 130.1, 129.1, 129.0, 128.6, 128.4,
127.0, 126.4, 84.4, 81.1, 79.1, 76.4, 75.6, 75.1, 74.3, 72.1, 71.9,
58.5, 54.7, 52.8, 45.6, 43.7, 43.2, 35.6, 26.9, 26.0, 22.8, 22.2,
20.9, 14.9, 9.7; ESI-MS (ES+) (m/z) calcd for C49H54N2O15
911.35, found 911.47 (MH+); melting point 182-184 °C.
P EG 2′-P a clita xel Glycin a te: Com p ou n d 10. To a solu-
tion of 6 (2.10 g, 1.85 mmol) in DCM (200 mL) was added
4-piperidinopiperidine (0.281 g, 0.167 mmol) and the reaction
was stirred for 3 h at room temperature. To the reaction
mixture was added 910 (15.0 g, 0.375 mmol), DMAP (0.186 g,
1.52 mmol), and EDC (0.288 g, 1.50 mmol) and stirring was
continued for 12 h. The solution was washed with 0.1 M HCl
(2 × 200 mL) and water (200 mL), dried (MgSO4), and filtered,
the solvent evaporated under reduced pressure, and the
residue crystallized from dimethylformamide/isopropyl alcohol
(DMF/IPA ) 1:4, 300 mL) to give 10 (12.88 g, 0.284 mmol,
82%). 13C NMR (67.8 MHz, CDCl3) δ 203.0, 170.4, 169.2, 168.9,
167.2, 166.6, 166.2, 156.0, 141.9, 136.3, 133.1, 132.3, 131.4,
129.6, 128.7, 128.6, 128.2, 128.0, 126.8, 126.3, 83.9, 80.6, 78.5,
75.9, 75.1, 74.6, 74.1, 63.9, 58.0, 52.6, 45.3, 42.8, 35.3, 35.1,
26.4, 22.3, 21.7, 20.5, 14.4, 9.3.
2′-P a clita xel Glycin a te: Com p ou n d 4. To a solution of
6 (1.00 g, 0.917 mmol) in DCM (50 mL) was added 4-piperid-
nopiperidine (0.917 mmol, 0.157 g) and the mixture was stirred
for 2 h at room temperature. The solution was concentrated
to about 2 mL by rotary evaporation and 50 mL of hexane was
added to precipitate the product. The resulting mixture was
centrifuged and the supernatant decanted. The hexane wash
J O034077S
4896 J . Org. Chem., Vol. 68, No. 12, 2003