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E. J. Roh et al. / Bioorg. Med. Chem. 10 (2002) 3145–3151
(m, 1H), 4.82 (d, J=7.3 Hz, 1H), 5.54–5.62 (m, 4H),
6.11–6.18 (m, 1H), 6.21 (s, 1H), 6.45–6.61 (m, 1H),
7.19–7.47 (m, 8H), 8.05 (d, J=7.14 Hz, 2H); 13C NMR
(CDCl3) d 8.27, 9.01, 9.58, 11.28, 12.72, 13.65, 14.87,
19.21, 20.86, 21.31, 21.89, 22.86, 27.91, 29.23, 34.07,
35.62, 43.19, 45.62, 54.96, 58.59, 72.18, 72.22, 73.48,
74.98, 75.59, 79.05, 81.09, 84.42, 122.79, 127.05, 128.28,
128.72, 128.96, 129.16, 130.24, 130.98, 131.22, 131.83,
133.07, 133.72, 138.07, 142.16, 146.50, 165.81, 166.99,
170.38, 171.28, 172.68, 203.69; HRMS (FAB) calcd for
C48H58NO14 (M+H+) 872.3857, found 872.3859.
127.18, 128.76, 129.09, 129.37, 129.48, 130.48, 130.58,
133.63, 133.83, 134.08, 134.24, 138.19, 138.57, 142.05,
142.34, 153.07, 154.19, 157.19, 167.43, 168.78, 170.67,
171.64, 203.99; HRMS (FAB) calcd for C48H60NO14
(M+H+) 874.4014, found 874.3978.
30 - N - Phenylpropynoyl - 30 - N - debenzoylpaclitaxel (1t).
1
Yield 13 mg (31%: overall yield from 50 mg of 4); H
NMR (CDCl3, selected diagnostic peaks) d 1.07 (s, 3H),
1.26 (s, 4H), 1.63 (s, 4H), 1.67 (s, 3H), 1.89 (s, 3H), 2.08
(d, J=8.96 Hz, 2H), 2.24 (s, 3H), 2.46–2.56 (m, 2H),
3.22 (d, J=10.22 Hz, 1H), 3.71 (d, J=7.11 Hz, 1H),
3.82 (d, J=9.92 Hz, 2H), 4.06–4.12 (m, 2H), 4.22 (d,
J=8.38 Hz, 1H), 4.42 (d, J=8.22 Hz, 2H), 4.61 (t,
J=9.05 Hz, 1H), 4.89 (d, J=7.69 Hz, 1H), 5.61 (d,
J=7.12 Hz, 1H), 6.26–6.29 (m, 2H), 7.35–7.71 (m,
12H), 8.02 (d, J=8.47 Hz, 2H); 13C NMR (CDCl3) d
9.52, 14.93, 20.86, 21.43, 21.89, 26.73, 35.41, 43.13,
45.53, 46.12, 47.62, 58.44, 62.61, 64.72, 66.26, 71.35,
72.06, 74.99, 75.51, 79.31, 80.70, 83.43, 84.37, 98.50,
122.23, 124.52, 125.44, 126.52, 126.94, 127.12, 128.62,
128.88, 129.03, 129.31, 130.13, 133.92, 136.94, 142.44,
167.03, 170.02, 170.61, 171.33, 203.73; HRMS (FAB)
calcd for C49H52NO14 (M+H+) 878.3388, found
878.3396.
30-N-(3-Cyclopentylpropanoyl)-30-N-debenzoylpaclitaxel
(1q). Yield 18 mg (43%: overall yield from 50 mg of 4);
1H NMR (CDCl3, selected diagnostic peaks) d 1.15 (s,
3H), 1.26 (s, 4H), 1.53–1.57 (m, 6H), 1.68 (s, 7H), 1.82–
1.91 (m, 5H), 2.19–2.34 (m, 10H), 2.45–2.55 (m, 2H),
3.47 (d, J=2.3 Hz, 1H), 3.75 (d, J=7.2 Hz, 1H), 4.18
(d, J=8.5 Hz, 1H), 4.29 (d, J=8.3 Hz, 1H), 4.32–4.48
(m, 1H), 4.93 (d, J=9.4 Hz, 1H), 5.57 (d, J=8.9 Hz,
1H), 5.67 (d, J=7.0 Hz, 1H), 6.18–6.28 (m, 3H), 7.35–
7.62 (m, 8H), 8.10 (d, J=8.5 Hz, 2H); 13C NMR
(CDCl3) d 9.56, 14.85, 20.88, 21.90, 22.62, 25.07, 26.81,
31.88, 32.32, 32.38, 35.58, 35.89, 39.56, 43.19, 45.56,
54.51, 58.58, 72.19, 72.34, 73.18, 74.93, 75.56, 79.03,
81.07, 84.39, 126.96, 128.28, 128.73, 128.96, 129.07,
130.24, 133.10, 133.73, 138.04, 142.11, 167.00, 170.27,
171.30, 172.84, 173.07, 203.69; HRMS (FAB) calcd for
C48H60NO14(M+H+) 874.4014, found 874.4019.
30-N-Nonanoyl-30-N-debenzoylpaclitaxel (1u). Yield 18
1
mg (43%: overall yield from 50 mg of 4); H NMR
(CDCl3, selected diagnostic peaks) d 0.86 (t, J=6.9 Hz,
3H), 1.15–1.26 (m, 17H), 1.51–1.59 (m, 2H), 1.68 (s,
4H), 1.82–1.91 (m, 5H), 2.17–2.35 (m, 10H), 2.47–2.54
(m, 2H), 3.51 (d, J=5.1 Hz, 1H), 3.78 (d, J=6.8 Hz,
1H), 4.18 (d, J=8.4 Hz, 1H), 4.29 (d, J=8.3 Hz, 1H),
4.39–4.42 (m, 1H), 4.67 (s, 1H), 4.93 (d, J=9.1 Hz, 1H),
5.55 (d, J=8.7 Hz, 1H), 5.67 (d, J=6.9 Hz, 1H), 6.21 (t,
J=8.7 Hz, 3H), 7.33–7.64 (m, 8H), 8.11 (d, J=7.5 Hz,
2H); 13C NMR (CDCl3) d 9.57, 14.08, 14.84, 20.87,
22.61, 25.74, 26.84, 29.10, 29.21, 29.25, 31.78, 35.63,
36.66, 43.21, 45.59, 54.55, 58.61, 72.36, 73.17, 74.97,
75.59, 79.04, 81.11, 84.41, 126.98, 128.28, 128.72,
128.98, 129.13, 130.24, 133.15, 133.72, 138.08, 142.10,
167.01, 170.27, 171.28, 172.83, 173.00, 203.68; HRMS
(FAB) calcd for C49H64NO14 (M+H+) 890.4327, found
890.4324.
30-N-Octanoyl-30-N-debenzoylpaclitaxel (1r). Yield 22
1
mg (52%: overall yield from 50 mg of 4); H NMR
(CDCl3, selected diagnostic peaks) d 0.84 (t, J=6.6 Hz,
3H), 1.15–1.26 (m, 13H), 1.51–1.57 (m, 2H), 1.63 (s,
2H), 1.81 (s, 2H), 2.18 (t, J=7.6 Hz, 2H), 2.23–2.34 (m,
7H), 2.47–2.59 (m, 2H), 3.72 (s, 1H), 3.77 (d, J=6.9 Hz,
1H), 4.18 (d, J=8.4 Hz, 1H), 4.28 (d, J=8.4 Hz, 1H),
4.32–4.42 (m, 1H), 4.67 (s, 1H), 4.93 (d, J=8.3 Hz, 1H),
5.57 (dd, J=2.4, 8.9 Hz, 1H), 5.67 (d, J=7.0 Hz, 1H),
6.19 (t, J=8.7 Hz, 1H), 6.35 (d, J=8.9 Hz, 1H), 7.29–
7.64 (m, 8H), 8.10 (d, J=7.4 Hz, 2H); 13C NMR
(CDCl3) d 9.58, 14.05, 14.82, 20.87, 21.89, 22.57, 25.74,
26.80, 28.94, 29.14, 31.62, 35.62, 36.61, 43.19, 45.61,
54.56, 58.55, 72.15, 72.28, 73.16, 74.96, 75.59, 78.92,
81.09, 84.39, 126.97, 128.23, 128.71, 128.94, 129.15,
130.22, 133.13, 133.69, 138.09, 142.06, 166.93, 170.28,
171.27, 172.82, 173.15, 203.69; HRMS (FAB) calcd for
C48H61NO14Na (M+Na+) 898.3990, found 898.3987.
30 - N - (10 - Undecenoyl) - 30 - N - debenzoylpaclitaxel (1v).
1
Yield 21 mg (47%: overall yield from 50 mg of 4); H
NMR (CDCl3, selected diagnostic peaks) d 1.14–1.33 (m,
10H), 1.51–1.57 (m, 2H), 1.67 (s, 2H), 1.81 (s, 2H), 1.87–
2.04 (m, 4H), 2.18 (t, J=7.3 Hz, 2H), 2.24–2.34 (m, 6H),
2.47–2.59 (m, 2H), 3.65 (s, 1H), 3.77 (d, J=6.8 Hz, 1H),
4.18 (d, J=8.4 Hz, 1H), 4.28 (d, J=8.4 Hz, 1H), 4.32–4.42
(m, 1H), 4.67 (s, 1H), 4.91–5.00 (m, 3H), 5.57 (d, J=8.8
Hz, 1H), 5.67 (d, J=6.9 Hz, 1H), 5.75–5.84 (m, 1H), 6.19
(t, J=8.6 Hz, 1H), 6.28–6.33 (m, 2H), 7.31–7.64 (m, 8H),
8.10 (d, J=8.1 Hz, 2H); 13C NMR (CDCl3) d 9.57, 14.83,
20.87, 21.89, 22.60, 25.72, 26.81, 28.84, 29.03, 29.17, 29.23,
29.26, 33.75, 35.60, 36.61, 43.19, 45.60, 54.55, 58.55, 72.15,
72.30, 73.15, 74.95, 75.58, 78.96, 81.08, 84.39, 114.17,
126.97, 128.25, 128.71, 128.95, 129.13, 129.62, 130.22,
133.11, 133.71, 138.07, 139.14, 142.07, 166.95, 170.27,
171.28, 172.83, 173.06, 203.68; HRMS (FAB) calcd for
C51H66NO14(M+H+) 916.4483, found 916.4481.
30-N-(trans-2-Ethyl-2-hexenoyl)-30-N-debenzoylpaclitaxel
(1s). Yield 14 mg (34%: overall yield from 50 mg of 4);
1H NMR (CDCl3, selected diagnostic peaks) d 1.15 (s,
3H), 1.26 (s, 4H), 1.59 (s, 12H), 1.68 (s, 3H), 1.80–2.04
(m, 8H), 2.36 (s, 5H), 2.49 (s, 3H), 2.52–2.63 (m, 2H),
3.33 (d, J=5.1 Hz, 1H), 3.79 (d, J=7.0 Hz, 1H), 4.18
(d, J=8.5 Hz, 1H), 4.29 (d, J=8.4 Hz, 1H), 4.35–4.42
(m, 1H), 4.51 (s, 1H), 4.64–4.68 (m, 2H), 4.94 (d, J=7.8
Hz, 1H), 5.29 (d, J=8.9 Hz, 1H), 5.68 (t, J=9.6 Hz,
2H), 6.28 (s, 2H), 7.39–7.61 (m, 8H), 8.09 (d, J=7.3 Hz,
2H); 13C NMR (CDCl3) d 9.96, 15.24, 19.93, 21.24,
22.17, 22.34, 23.0, 27.22, 31.30, 35.97, 43.62, 46.04,
56.97, 59.0, 59.95, 72.56, 72.81, 73.74, 75.33, 75.96,
79.45, 79.80, 80.86, 81.20, 81.60, 84.79, 101.95, 126.54,