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D. Guenard et al. / Bioorg. Med. Chem. 8 (2000) 145±156
152
0.1 mmol, 8 mL toluene) with octanoic acid by method
B (2 h) aorded, after work up and puri®cation by pre-
parative TLC (CH2Cl2:MeOH, 96:4), 7-octanoyl 20-troc
docetaxel (60 mg, 52%) and 10-heptanoyl 20-troc doc-
etaxel (41 mg, 35%) along with starting material
(9.5 mg, 9%). The troc protective groups were removed
for each compound as described in general methods. 7-
octanoyl 20-troc docetaxel (50 mg) aorded after 1 h at
room temperature and puri®cation by preparative TLC
(CH2Cl2:MeOH, 96:4) 7-octanoyldocetaxel 8a (25 mg,
59%) along with starting material (19 mg, 38%), 7-
173.64 (CO); MS-FAB+ m/z 1110 (M+Na+), 1088
(M+H+), 830, 807.
Preparation of compounds 10a,b,c. Esteri®cation of 20-
(2,2,2-trichloroethyloxycarbonyl) docetaxel (255 mg,
0.25 mmol, 15 mL toluene) with undecanoic acid by
method A (24 h) aorded, after work up and puri®ca-
tion by column silica gel chromatography (EtOAc:hep-
tane, 1:1), then preparative TLC (EtOAc:heptane, 1:1),
7-undecanoyl 20-troc docetaxel (91 mg, 32%), 10-undec-
anoyl 20-troc docetaxel (65 mg, 23%) and 7,10-diundec-
anoyl 20-troc docetaxel (10.4 mg, 3%). The troc
protective groups were removed for each compound as
described in general methods). 7-Undecanoyl 20-troc
docetaxel (65 mg) aorded after 4 h at 40 ꢀC and pur-
i®cation by preparative TLC (EtOAc:heptane, 1:1), 7-
undecanoyldocetaxel (10a) (45.7 mg, 84%): 1H NMR
(300 MHz, CDCl3) d 0.81 (t, J=7 Hz, CH3), 1.20 (m,
CH2), 1.48 (m, CH2), 2.16 (m, CH2±CO), 5.23 (s, C-
10H), 5.40 (m, C-7H); 13C NMR (75 MHz, CDCl3) d
13.66 (CH3), 21.96 (CH2), 24.29 (CH2), 28.67 (CH2),
28.90 (CH2), 29.01 (CH2), 31.35 (CH2), 35.28 (CH2),
171.99 (CO); MS-FAB+ m/z 982 (M+Li+), 701. 10-
Undecanoyl 20-troc docetaxel (45 mg) aorded after 4 h
at 40 ꢀC and puri®cation by preparative TLC (EtOAc:
heptane, 1:1) 10-undecanoyldocetaxel (10b) (24.5 mg,
1
octanoyldocetaxel (8a): H NMR (300 MHz, CDCl3) d
0.83 (t, J=7 Hz, CH3), 1.29 (m, CH2), 1.48 (m, CH2),
2.15 (m, CH2±CO), 5.23 (s, C-10H), 5.40 (m, C-7H); 13
C
NMR (75 MHz, CDCl3) d 14.43 (CH3), 21.72 (CH2),
24.06 (CH2), 28.10 (CH2), 28.22 (CH2), 30.86 (CH2),
35.02 (CH2), 171.75 (CO chain); MS-FAB+ m/z 956
(M+Na+), 675. 10-Heptanoyl 20-troc docetaxel (40 mg)
aorded, after 45 min at room temperature and puri-
®cation by preparative TLC (CH2Cl2:MeOH, 95:5)
7,10-dioctanoyldocetaxel 8b (16 mg, 47%) along with
starting material (5 mg, 12%). 7,10-Dioctanoyldocetaxel
1
(8b). H NMR (300 MHz, CDCl3) d 0.84 (t, J=7 Hz,
CH3), 1.24 (m, CH2), 2.43 (m, CH2±CO), 4.35 (m, C-
7H), 6.22 (s, C-10H); 13C NMR (75 MHz, CDCl3) d
14.47 (CH3), 23.03 (CH2), 25.27 (CH2), 29.31 (CH2),
29.46 (CH2), 32.07 (CH2), 34.62 (CH2), 173.50 (CO);
MS-FAB+ m/z 956 (M+Na+), 675.
1
74%): H NMR (300 MHz, CDCl3) d 0.96 (t, J=7 Hz,
CH3), 1.35 (m, CH2), 1.78 (m, CH2), 2.56 (m, CH2±CO),
4.47 (m, C-7H), 6.35 (s, C-10H); 13C NMR (75 MHz,
CDCl3) d 14.55 (CH3), 23.12 (CH2), 25.29 (CH2), 29.54
(CH2), 29.69 (CH2), 29.90 (CH2), 32.35 (CH2), 36.01
(CH2), 173.57 (CO); MS-FAB+ m/z 982 (M+Li+), 701.
7,10-Diundecanoyl 20-troc docetaxel (9 mg) aorded
after 5 h at 40 ꢀC and overnight at room temperature
and puri®cation by preparative TLC (EtOAc:heptane,
1:1) 7,10-diundecanoyldocetaxel (10c) (5.6 mg, 72%):
1H NMR (300 MHz, CDCl3) d 0.96 (m, CH3), 1.33 (m,
CH2), 1.63 (m, CH2), 2.35 (m, CH2±CO), 5.63 (m, C-
7H), 6.37 (s, C-10H); MS-FAB+ m/z 1150 (M+Li+),
869.
Preparation of compounds 9a,b,c. Esteri®cation of 20-
(2,2,2-trichloroethyloxycarbonyl) docetaxel (265 mg,
0.27 mmol, 20 mL toluene) with nonanoic acid by
method A (1 h) aorded, after work up and puri®cation
by column silica gel chromatography (CH2Cl2:MeOH,
99.5:0.5), 7-nonanoyl 20-troc docetaxel (63 mg, 21%),
10-nonanoyl 20-troc docetaxel (45 mg, 15%) and 7,10-
dinonanoyl 20-troc docetaxel (179 mg, 53%). The troc
protective groups were removed for each compound as
described in general methods. 7-Nonanoyl 20-troc doc-
etaxel (70 mg) aorded after 3 h at room temperature
and puri®cation by preparative TLC (EtOAc:heptane,
1:1) 7-nonanoyldocetaxel (9a) (32.4 mg, 55%): 1H NMR
(300 MHz, CDCl3) d 0.88 (t, J=7 Hz, CH3), 1.28 (m,
CH2), 1.53 (m, CH2), 2.25 (m, CH2±CO), 5.28 (s, C-
10H), 5.46 (m, C-7H); MS-FAB+ m/z 970 (M+Na+),
948 (M+H+), 689, 667. 10-Nonanoyl 20-troc docetaxel
(56 mg) aorded after 2 h at 60 ꢀC and puri®cation by
preparative TLC (EtOAc:heptane, 1:1) 10-nonanoyl-
docetaxel (9b) (37 mg, 82%): 1H NMR (300 MHz,
CDCl3) d 0.91 (t, J=7 Hz, CH3), 1.28 (m, CH2), 1.72
(m, CH2), 2.29 (m, CH2±CO), 4.43 (m,C-7H), 6.29 (s, C-
10H); 13C NMR (75 MHz, CDCl3) d 15.02 (CH3), 23.12
(CH2), 25.33 (CH2), 29.59 (CH2), 32.30 (CH2), 36.06
(CH2), 170.72 (CO); MS-FAB+ m/z 970 (M+Na+),
948 (M+H+), 689, 667. 7,10-Dinonanoyl 20-troc doc-
etaxel (316 mg) aorded after 5 h at room temperature
and puri®cation by preparative TLC (EtOAc:heptane,
1:1) 7,10-dinonanoyldocetaxel (9c) (77 mg, 28%): 1H
NMR (300 MHz, CDCl3) d 0.91 (m, CH3), 1.29 (m,
CH2), 1.65 (m, CH2), 2.32 (m, CH2±CO), 5.56 (m, C-
7H), 6.31 (s, C-10H); 13C NMR (75 MHz, CDCl3) d
14.62 (CH3), 23.19 (CH2), 24.98 (CH2), 29.66 (CH2),
29.80 (CH2), 32.39 (CH2), 34.72 (CH2), 172.06 (CO),
Preparation of compounds 11a,b. Esteri®cation of 20-
(2,2,2-trichloroethyloxycarbonyl) docetaxel (474 mg,
0.48 mmol, 10 mL toluene) with myristic acid by method
A (6.5 h) aorded, after work up and puri®cation by
column silica gel chromatography (EtOAc:heptane,
30:70), 7-myristyl 20-troc docetaxel (152 mg, 26%), 10-
myristyl 20-troc docetaxel (187 mg, 32%).The troc pro-
tective groups were removed for each compound as
described in general methods. 7-Myristyl 20-troc doc-
etaxel (110 mg) aorded after 4 h at room temperature
and 1 h at 60 ꢀC and puri®cation by preparative TLC
(EtOAc:heptane, 30:70) 7-myristyldocetaxel (11a)
1
(63.4 mg, 68%): H NMR (300 MHz, CDCl3) d 0.80 (t,
J=7 Hz, CH3), 1.18 (m, CH2), 1.55 (m, CH2), 2.23 (m,
CH2±CO), 5.22 (s, C-10H), 5.68 (m, C-7H); 13C NMR
(75 MHz, CDCl3) d 14.44 (CH3), 23.04 (CH2), 25.19
(CH2), 29.42 (CH2), 29.59 (CH2), 29.69 (CH2), 29.80
(CH2), 32.27 (CH2), 36.19 (CH2), 172.87 (CO); MS-
FAB+ m/z 1024 (M+Li+), 743. 10-Myristyl 20-troc
docetaxel (157 mg) aorded after 1.5 h at 60 ꢀC and
puri®cation by preparative TLC (EtOAc:heptane, 1:1)
10-myristyldocetaxel (11b) (121 mg, 91%): 1H NMR