1400
Vol. 50, No. 10
(m/z): 535 (MϩH)ϩ; HR-MS Calcd for C29H43O9: 535.2907. Found,
535.2916; IR: 3442, 2929, 2856, 1720, 1685, 1450 cmϪ1; [a]D23 Ϫ37.3° (cϭ
0.65, CHCl3).
give the title compound (11.5 g) as a white solid, which contained a small
amount of pyridine and was used for the next reaction without further purifi-
cation. 1H-NMR (CDCl3) d: 1.06 (3H, s), 1.20 (3H, s), 1.61 (1H, br s), 1.88
(3H, s), 2.05—2.40 (4H, m), 2.25 (3H, s), 2.31 (3H, s), 2.80—2.95 (1H, m),
4.01 (1H, d, Jϭ7.1 Hz), 4.16 (1H, d, Jϭ8.5 Hz), 4.35 (1H, d, Jϭ8.5 Hz),
4.80—4.90 (1H, br s), 4.95 (1H, d, Jϭ8.8 Hz), 5.53 (1H, dd, Jϭ7.8,
10.3 Hz), 5.69 (1H, d, Jϭ7.1 Hz), 6.73 (1H, s), 7.50 (2H, t, Jϭ7.8 Hz), 7.63
(1H, t, Jϭ7.8 Hz), 8.10 (2H, d, Jϭ7.8 Hz), 8.20 (1H, s); FAB-MS (m/z): 705
(MϩH)ϩ.
(1S,2S,3R,4S,5R,8R,9S,10R,13S)-4-acetoxy-2-benzoyloxy-1,13-dihy-
droxy-5,20-epoxy-9,10-(isopropylidenedioxy)tax-6,11-diene (10) To
a
solution of 9 (1.0 g, 1.71 mmol) and DMAP (2.1 g, 17.1 mmol) in CH2Cl2
(30 ml) was added Tf2O (1.15 ml, 6.83 mmol) with ice cooling, and the mix-
ture was stirred at the same temperature for 6 h. The reaction mixture was
poured into a mixture of AcOEt and saturated aqueous NaHCO3. The layers
were separated, and the aqueous layer was extracted with AcOEt. The com-
bined organic layer was washed with water, brine, and dried over Na2SO4.
The solvent was removed under reduced pressure, and the residue was chro-
matographed on silica gel eluted with CHCl3–acetone (50 : 1 (v/v)). The elu-
ate was concentrated under reduced pressure, and the residue was triturated
with CHCl3–n-hexane. The resulting powder was collected by filtration to
give the title compound (0.42 g, 43%) as a white powder, mp 143—144 °C.
1H-NMR (CDCl3) d: 1.14 (3H, s), 1.42 (3H, s), 1.53 (3H, s), 1.54 (3H, s),
1.59 (3H, s), 1.73 (1H, s), 1.91 (3H, s), 2.09 (1H, dd, Jϭ7.3, 15.1 Hz), 2.16
(1H, d, Jϭ8.1 Hz), 2.32—2.39 (1H, m), 2.34 (3H, s), 3.22 (1H, d,
Jϭ5.8 Hz), 4.03 (1H, d, Jϭ7.3 Hz), 4.26 (1H, d, Jϭ8.0 Hz), 4.34 (1H, d,
Jϭ8.1 Hz), 4.78—4.81 (1H, m), 4.82 (1H, d, Jϭ4.1 Hz), 5.53 (1H, d,
Jϭ7.5 Hz), 5.67 (1H, dd, Jϭ3.2, 10.2 Hz), 5.92 (1H, d, Jϭ6.0 Hz), 6.10 (1H,
d, Jϭ10.2 Hz), 7.48 (2H, t, Jϭ7.8 Hz), 7.60 (1H, t, Jϭ7.8 Hz), 8.15 (2H, d,
Jϭ7.8 Hz); FAB-MS (m/z): 569 (MϩH)ϩ; HR-MS Calcd for C32H41O9:
569.2751. Found, 569.2764; IR: 3507, 2975, 1725, 1689, 1482 cmϪ1; [a]D24
Ϫ12.9° (cϭ1.04, CHCl3).
(1S,2S,3R,4S,5R,7S,8R,10R,13S)-4-Acetoxy-2-benzoyloxy-5,20-epoxy-
9-oxo-1,10,13-trihydroxytax-6,11-diene (6) To a solution of 5 (11.5 g) in
THF (115 ml) was added Me2NH (2.0 M in THF, 12.3 ml, 24.5 mmol), and
the mixture was stirred at room temperature for 1.5 h. After adding ethyl for-
mate (2.0 ml, 24.5 mmol) to the reaction mixture, the resulting mixture was
stirred at the same temperature for further 15 min. The reaction mixture was
concentrated under reduced pressure and the residue was suspended in a
mixture of THF (5 ml) and 1,4-dioxane (50 ml). To this suspension was
added DBU (5 ml), and the mixture was stirred at 100 °C for 30 min. The re-
action mixture was poured into a cold mixture of 1 N HCl and AcOEt. The
layers were separated and the aqueous layer was extracted with AcOEt. The
combined organic layer was washed with saturated aqueous NaHCO3, brine
and dried over Na2SO4. The solvent was removed under reduced pressure,
and the residue was chromatographed on silica gel eluted with CHCl3–
AcOEt (1 : 1 (v/v)). The eluate was concentrated under reduced pressure,
and the residue was triturated with n-hexane–AcOEt. The resulting precipi-
tate was collected by filtration to give the title compound (6.8 g, 79%) as a
1
white solid, mp 160—162 °C. H-NMR (CDCl3) d: 1.07 (3H, s), 1.13 (3H,
s), 1.66 (1H, br s), 1.92 (3H, s), 1.95—2.35 (3H, m), 2.00 (3H, d, Jϭ1.0 Hz),
2.31 (3H, s), 4.18 (1H, d, Jϭ6.5 Hz), 4.23 (1H, d, Jϭ1.5 Hz), 4.30 (1H, d,
Jϭ8.3 Hz), 4.43 (1H, d, Jϭ8.3 Hz), 4.82—4.93 (1H, br s), 5.02 (1H, s), 5.10
(1H, d, Jϭ5.4 Hz), 5.76 (1H, d, Jϭ9.8 Hz), 5.81 (1H, d, Jϭ6.5 Hz), 6.04
(1H, dd, Jϭ5.4, 9.8 Hz), 7.49 (2H, t, Jϭ7.8 Hz), 7.62 (1H, t, Jϭ7.8 Hz),
8.14 (2H, d, Jϭ7.8 Hz); FAB-MS (m/z): 527 (MϩH)ϩ; Anal. Calcd for
C29H34O9·0.5H2O: C, 65.03; H, 6.59. Found: C, 65.07; H, 6.64; IR: 3461,
2991, 2898, 1710, 1488 cmϪ1; [a]D24 Ϫ89.4° (cϭ0.17, CHCl3).
References and Notes
1) Wani M. C., Taylor H. L., Wall M. E., Coggon P., McPhali A. T., J.
Am. Chem. Soc., 93, 2325—2327 (1971).
2) Guéritte-Voegelein F., Guénard D., Lavelle F., Le Goff M.-T., Mangatal
L., Potier P., J. Med. Chem., 34, 992—998 (1991).
3) For review see: Suffness M., Annu. Rep. Med. Chem., 28, 305—314
(1993).
4) For review see: Guénard D., Guéritte-Voegelein F., Potier P., Acc.
Chem. Res., 26, 160—167 (1993).
5) Chen S.-H., Huang S., Kant J., Fairchild C., Wei J., Farina V. J., Org.
Chem., 58, 5028—5029 (1993).
6) Iimura S., Uoto K., Ohsuki S., Chiba J., Yoshino T., Iwahana M.,
Jimbo T., Terasawa H., Soga T., Bioorg. Med. Chem. Lett., 11, 407—
410 (2001)
7) Altstadt T. J., Fairchild C. R., Golik J., Johnston K. A., Kadow J. F.,
Lee F. Y., Long B. H., Rose W. C., Vyas D. M., Wong H., Wu M.-J.,
Wittman M. D., J. Med. Chem., 44, 4577—4583 (2001).
8) Chaudhary A. G., Rimoldi J. M., Kingston D. G. I., J. Org. Chem., 58,
3798—3799 (1993).
(1S,2S,3R,4S,5R,7S,8R,10R,13S)-4-Acetoxy-2-benzoyloxy-5,20-epoxy-
9-oxo-1,10,13-trihydroxytax-11-ene (7) (General Procedure, Entry 7)
6
(100 mg, 190 mmol) was hydrogenated (balloon) in EtOH (3 ml) over 10%
Pd–C (100 mg) for 14 h. After removal of the catalyst by filtration, the fil-
trate was concentrated under reduced pressure and the residue was chro-
matographed on silica gel eluted with CHCl3–MeOH (50 : 1 (v/v)). The elu-
ate was concentrated under reduced pressure to give the title compound
(100 mg, 99%) as a white amorphous powder. 1H-NMR (CDCl3) d: 1.06
(3H, s), 1.09 (3H, s), 1.50—1.55 (1H, m), 1.61 (1H, br s), 1.80 (3H, s),
1.90—2.41 (6H, m), 2.06 (3H, s), 2.29 (3H, s), 3.92 (1H, d, Jϭ7.3 Hz), 4.17
(1H, d, Jϭ1.5 Hz), 4.22 (1H, d, Jϭ8.3 Hz), 4.33 (1H, d, Jϭ8.3 Hz), 4.82—
4.92 (1H, m), 4.96 (1H, dd, Jϭ3.2, 9.6 Hz), 5.24 (1H, d, Jϭ1.5 Hz), 5.62
(1H, d, Jϭ7.3 Hz), 7.48 (2H, t, Jϭ7.3 Hz), 7.61 (1H, t, Jϭ7.3 Hz), 8.12 (2H,
d, Jϭ7.3 Hz); FAB-MS (m/z): 529 (MϩH)ϩ; HR-MS Cacld for C29H37O9:
529.2438. Found, 529.2448; IR: 3451, 2956, 1714, 1600, 1488 cmϪ1; [a]D25
Ϫ25.2° (cϭ1.04, CHCl3).
(1S,2S,3R,4S,5R,7S,8R,10R,13S)-4-Acetoxy-2-cyclohexanecarbony-
loxy-5,20-epoxy-9-oxo-1,10,13-trihydroxytax-11-ene (8) (General Proce-
dure, Entry 1) 6 (100 mg, 190 mmol) was hydrogenated (balloon) in
AcOEt (3 ml) over PtO2 (50 mg) for 1.5 h. After removal of the catalyst by
filtration, the filtrate was concentrated under reduced pressure and the
residue was triturated with CHCl3. The resulting powder was collected by
filtration to give the title compound (90 mg, 89%) as a white powder, mp
127—128 °C. 1H-NMR (CDCl3) d: 0.98 (3H, s), 1.07 (3H, s), 1.21—1.56
(7H, m), 1.64 (1H, m), 1.74 (3H, s), 1.78—1.80 (1H, m), 1.93—2.32 (8H,
m), 2.02 (3H, m), 2.18 (3H, s), 3.78 (1H, d, Jϭ7.1 Hz), 4.12 (1H, d,
Jϭ1.5 Hz), 4.19 (1H, d, Jϭ8.0 Hz), 4.47 (1H, d, Jϭ7.3 Hz), 4.84 (1H, m),
4.97 (1H, d, Jϭ9.5 Hz), 5.19 (1H, s), 5.38 (1H, d, Jϭ7.0 Hz); FAB-MS
9) Pulicani J.-P., Bouchard H., Bourzat J.-D., Commerçon A., Tetrahedron
Lett., 35, 9709—9712 (1994).
10) Ishiyama T., Iimura S., Yoshino T., Chiba J., Uoto K., Terasawa H.,
Soga T., Bioorg. Med. Chem. Lett. accepted.
11) Johnson R. A., Nidy E. G., Dobrowolski P. J., Gebhard I., Qualls S. J.,
Wicnienski N. A., Kelly R. C., Tetrahedorn Lett., 35, 7893—7896
(1994).
12) A related O-formylation reaction; Barluenga J., Campos P. J., Gonza-
les-Nuñez E., Asensio G., Synthesis, 1985, 426—428 (1985).
13) After removal of the formyl group at the C-10 position with Me2NH,
the excess amount of Me2NH was treated with HCO2Me to afford
DMF and MeOH, which were easily removed by evaporation.
14) Poujol H., Mourabit A. A., Ahond A., Poupat C., Potier P.,
Tetrahedron, 53, 12575—12594 (1997).
15) Ishiyama T., Iimura S., Ohsuki S., Uoto K., Terasawa H., Soga T.,
Bioorg. Med. Chem. Lett., 12, 1083—1086 (2002).