X. Qi et al. / Tetrahedron 60 (2004) 3599–3603
3603
[MþNa]þ, calcd for C55H67NO14SSi Na¼1048.3931. Anal.
calcd for C55H67NO14SSi: C, 64.37; H, 6.58; N, 1.36; S,
3.12; found: C, 64.22; H, 6.63; N, 1.34; S, 3.12.
2.50–2.55 (m, 2H), 3.74 (d, J¼7.0 Hz, 1H), 4.05–4.11 (m,
1H), 4.13 (d, J¼8.4 Hz, 1H), 4.24 (d, J¼8.4 Hz, 1H), 4.39
(m, 1H), 4.91 (d, J¼8.0 Hz, 1H), 5.62 (d, J¼7.1 Hz, 1H),
5.66 (t, J¼7.8 Hz, 1H), 6.13 (t, J¼8.7 Hz, 1H), 6.26 (s, 1H),
7.05 (d, J¼8.0 Hz, 1H), 7.31–7.63 (m, 11H), 7.79 (d, J¼
7.7 Hz, 2H), 8.02 (d, J¼7.9 Hz, 2H); 13C NMR (CDCl3,
75 MHz) d 9.95, 15.32, 21.23, 22.27, 22.95, 27.15, 35.90,
43.50, 46.00, 47.48, 56.20, 58.91, 71.80, 72.54, 75.37,
75.89, 79.59, 81.39, 84.76, 127.45, 127.51, 128.86, 129.06,
129.14, 129.38, 129.51, 130.50, 132.36, 133.24, 134.17,
134.38, 138.99, 142.91, 167.32, 167.62, 170.26, 171.36,
171.65, 204.06; HRMS (FAB) m/z¼892.2986 [MþNa]þ,
calcd for C47H51NO13SNa¼892.2965.
4.1.3. 20-Deoxy-20-thioacetoxypaclitaxel 7a. To a vigorous
stirred solution of compound 6a accompanied by 6b
(140 mg, 0.136 mmol) in dry THF (10 mL) was added
1.4 mL of hydrogen fluoride–pyridine (70:30) at 0 8C under
N2. After 10 min stirring at 0 8C, the reaction mixture was
then stirred for another 5 h at room temperature. Water
(10 mL) was added to quench the reaction and the mixture
was extracted with ethyl acetate (4£20 mL). The combined
organic layer was washed subsequently with dilute aqueous
NaHCO3 and brine, dried over Na2SO4, and concentrated in
vacuo. Purification of the crude product by flash chroma-
tography (EtOAc/hexane, 1:1) afforded small amount of 7b
and the corresponding product 7a as a white solid (100 mg,
0.11 mmol, 82%). An analytical sample was obtained by
re-crystallization (distilled EtOAc/hexane) as white crystal-
Acknowledgements
We thank Hanmi Pharmaceutical Co., Ltd for the generous
donation of 10-deacetylbaccatin III. This work was
supported by Korea Science and Engineering Foundation
(R14-2003-014-01001-0) and the Brain Korea 21 Program.
1
line: mp 181–183 8C; [a]1D3¼210.78 (c¼0.77, CHCl3); H
NMR (CDCl3, 500 MHz) d 1.09 (s, 3H), 1.17 (s, 3H), 1.58
(s, 1H), 1.59 (s, 1H), 1.64 (s, 3H), 1.70–1.76 (m, 3H), 1.76
(s, 1H), 1.83–1.94 (m, 2H), 2.22 (s, 3H), 2.31 (s, 3H), 2.44
(s, 3H), 2.50–2.56 (m, 1H), 3.70 (d, J¼7.0 Hz, 1H), 4.12 (d,
J¼8.5 Hz, 1H), 4.26 (d, J¼8.4 Hz, 1H), 4.36–4.40 (m, 1H),
4.75 (d, J¼10.7 Hz, 1H), 4.93 (m, 1H), 5.58 (d, J¼7.1 Hz,
1H), 5.73 (dd, J¼9.0, 10.5 Hz, 1H), 6.03 (dd, J¼7.9, 9.0 Hz,
1H), 6.21 (s, 1H), 6.82 (d, J¼8.8 Hz, 1H), 7.23 (m, 2H),
7.36 (t, J¼7.6 Hz, 2H), 7.42–7.46 (m, 4H), 7.50–7.55 (m,
2H), 7.65 (t, J¼7.5 Hz, 1H), 7.72 (d, J¼7.2 Hz, 2H), 8.03
(d, J¼7.2 Hz, 2H); 13C NMR (CDCl3, 125 MHz) d 9.92,
15.17, 21.22, 22.22, 22.97, 30.91, 35.47, 35.88, 43.44,
45.93, 51.59, 55.61, 58.89, 71.51, 72.52, 75.36, 75.83,
76.73, 79.56, 81.29, 84.81, 127.33, 127.66, 129.02, 129.14,
129.36, 129.62, 130.49, 132.35, 133.25, 133.95, 134.24,
139.16, 142.79, 166.88, 167.32, 169.19, 170.28, 171.67,
196.38, 204.03; HRMS (FAB) m/z¼934.3083 [MþNa]þ,
calcd for C49H53NO14SNa¼934.3070. Anal. calcd for
C49H53NO14S: C, 64.53; H, 5.86; N, 1.54; S, 3.52; found:
C, 64.51; H, 5.99; N, 1.49; S, 3.45.
References and notes
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1557. (b) Lozynski, M.; Rusinska-Roszak, D. Tetrahedron
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4.1.4. 20-Deoxy-20-mercaptopaclitaxel 2a. To a solution of
7a (40 mg, 0.044 mmol) in MeOH (2 mL, degassed) was
added dropwise a solution of LiOH·H2O (1.85 mg,
0.044 mmol) in H2O (0.2 mL, degassed) during 0.5 h at
room temperature under N2 with vigorous stirring. After
another 30 min, the reaction mixture was poured into a
mixture of CHCl3–H2O (15:15 mL), and was acidified with
two or three drops of 1 N HCl to pH 1–2. The water layer
was extracted with CHCl3 (3£10 mL), and the combined
organic layer was washed with water (15 mL), dried over
Na2SO4, and concentrated in vacuo. The crude product was
purified by preparative TLC (2% MeOH/CHCl3) in dark
place to afford final product 2a as a white solid (25 mg,
0.029 mmol, 65%); mp 214–216 8C (dec.); [a]1D5¼217.68
(c¼1.00, MeOH); IR (KBr) 3463, 2984, 2937, 2552, 1721,
6. Qi, X.; Lee, S.-H.; Yoon, J.; Lee, Y.-S. Tetrahedron 2003, 59,
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´
´
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1
1642, 1610 cm21; H NMR (CDCl3, 300 MHz) d 1.11 (s,
3H), 1.18 (s, 3H), 1.65 (s, 3H), 1.74 (s, 1H), 1.85 (m, 1H),
1.88 (s, 3H), 2.03–2.09 (m, 3H), 2.20 (s, 3H), 2.22 (s, 3H),