B.S. Chhikara et al. / European Journal of Medicinal Chemistry 46 (2011) 2037e2042
2041
J ¼ 5.1 Hz, H-7ax), 1.72e1.78 (m, 1H, H-7eq), 1.54 (d, 2H, J ¼ 6.5 Hz,
NHCOCH2CH2),1.25 (d, 3H, J ¼ 6.5 Hz, 60-CH3),1.25 (br s,16H, 8 ꢁ CH2,
methylene envelope), 0.84e0.87 (m, 3H, CH3); 13C NMR (125 MHz,
(NHCOCH2), 35.33 (C30), 33.07 (C9), 29.32 (C7), 31.53, 31.27, 29.57,
29.27, 29.23, 29.12, 29.04, 28.98, 28.91, 28.83, 28.54, 27.63 (meth-
ylene carbons), 25.52 (NHCOCH2CH2), 22.90 (CH2CH3), 22.31
(SCH2), 18.02 (60-CH3) 13.74 (CH3); HR-MS (ESI-TOF): calcd. for
C41H55NO12S 785.3445; found, 824.1986 [M þ K]þ.
CDCl3,
d ppm): 213.90 (C13]O), 186.99 (C12]O), 186.54 (C5]O),
172.61 (NHeC]O),160.98 (C1),156.17 (C6),155.59 (C11),135.72 (C3)
135.44 (C10a),133.59 (C4a),133.58 (C6a),120.80 (C12a),119.82 (C2),
118.40 (C4),111.52 (C11a),111.33 (C5a),100.69 (C20), 76.51 (C8), 69.64
(C60), 69.60 (C50), 67.22 (C10), 65.53 (O]CeCH2OH), 56.64 (OCH3),
45.01 (NH-C40), 36.74 (NHCOCH2), 35.68 (C30), 33.91 (C9), 29.95 (C7),
31.87, 29.68, 29.59, 29.55, 29.44, 29.32, 29.29, 29.22 (methylene
carbons), 25.67 (NHCOCH2CH2), 22.64 (CH2CH3), 16.81 (60-CH3),
14.08 (CH3); HR-MS (ESI-TOF): calcd. for C39H51NO12 725.3411;
found, 748.2137 [M þ Na]þ and 764.1691 [M þ K]þ.
4.2.1.7. (8S,10S)-10-(4-(N-hexadecanoylamido)-5-hydroxy-6-
methyl-tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-
hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione
(8). Red brown solid (66 mg, 91.8% yield). IR (cmꢀ1, ATR): 3346.
2923, 2848, 1716 (C]O), 1642 (C]O str, amide), 1618, 1575, 1445,
1407, 1373, 1279, 1233, 1203, 1109, 1068, 1015, 844, 764; UV/vis
l
(nm): 478, 290, 254, 234; 1H NMR (500 MHz, CDCl3,
d
ppm): 13.98
(s,1H, PhOH),13.28 (s,1H, PhOH), 8.06 (d, J ¼ 7.8 Hz,1H, ArC2H), 7.80
(t, 1H, J ¼ 8.1 Hz, ArC3H), 7.40 (d, 1H, J ¼ 8.6 Hz, ArC4H), 7.26 (s, 1H,
NH), 5.76 (d,1H, J ¼ 8.5 Hz, OH), 5.50 (d, 1H, J ¼ 3.0 Hz, H-20), 5.30 (s,
1H, H-50), 4.76 (s, 2H, O]C13eCH2), 4.19e4.13 (m, 2H, H-10 and H-
40), 4.09 (s, 3H, OCH3), 3.64 (s, 1H, H-60), 3.30 (d, 1H, J ¼ 19.2 Hz, H-
9eq), 3.05 (d,1H, J ¼ 20.1 Hz, H-9ax), 2.34 (d,1H, J ¼ 13.4 Hz, H-30eq),
2.18 (dd, J ¼ 14.8 Hz, J ¼ 3.7 Hz, 1H, H-30ax), 2.10e2.13 (m, 2H, O]
CeCH2),1.87 (dd,1H, J ¼ 13.7 Hz, J ¼ 4.5 Hz, H-7ax),1.71e1.77 (m,1H,
H-7eq), 1.54e1.62 (m, 2H, NHCOCH2CH2), 1.29 (d, 3H, J ¼ 5.3 Hz, 60-
CH3), 1.23e1.25 (br s, 24H, 12 ꢁ CH2, methylene envelope),
4.2.1.5. (8S,10S)-10-(4-(N-tetradecanoylamido)-5-hydroxy-6-
methyl-tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-
hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione
(6). Red brown solid (63 mg, 90.8% yield). IR (cmꢀ1, ATR): 3346,
2923, 2848, 1719 (C]O), 1644 (C]O str, amide), 1614, 1575, 1445,
1407, 1280, 1205, 1017, 980; UV/vis
l (nm): 494, 477, 289, 249, 229;
1H NMR (500 MHz, CDCl3,
d
ppm): 13.92 (s, 1H, PhOH), 13.18 (s, 1H,
PhOH), 7.99 (d, J ¼ 7.6 Hz, 1H, ArC2H), 7.73 (t, 1H, J ¼ 8.3 Hz, ArC3H),
7.34 (d,1H, J ¼ 8.4 Hz, ArC4H), 7.24 (s,1H, NH), 5.85 (d,1H, J ¼ 8.4 Hz,
OH), 5.46 (d, 1H, J ¼ 3.7 Hz, H-20), 5.22 (s, 1H, H-50), 4.73 (s, 2H, O]
0.86e0.89 m, 3H, CH3); 13C NMR (125 MHz, CDCl3,
d ppm): 213.94
C
13eCH2), 4.12e4.16 (m, 2H, H-10 and H-40), 4.04 (s, 3H, OCH3), 3.61
(C13]O), 187.10 (C12]O), 186.65 (C5]O), 172.61 (NHeC]O), 161.01
(C1), 156.01 (C6), 155.64 (C11), 135.77 (C3) 135.48 (C10a), 133.61
(C4a), 133.55 (C6a), 120.83 (C12a), 119.46 (C2), 118.00 (C4), 111.16
(C11a),110.97 (C5a),104.60 (C20), 76.37 (C8), 69.26 (C60), 69.24 (C50),
66.83 (C10), 65.18 (O]CeCH2OH), 56.66 (OCH3), 44.60 (NH-C40),
36.38 (NHCOCH2), 33.56 (C30), 33.09 (C9), 29.58 (C7), 33.07, 33.04,
31.54, 31.53, 29.32, 29.28, 29.26, 29.24, 29.08, 29.04, 28.98, 28.96,
28.85 (methylene carbons), 25.31 (NHCOCH2CH2), 22.90 (CH2CH3),
16.44 (60-CH3) 13.74 (CH3); HR-MS (ESI-TOF): calcd. for C43H59NO12
781.4037; found, 804.2106 [M þ Na]þ.
(s, 1H, H-60), 3.22 (d, 1H, J ¼ 18.9 Hz, H-9eq), 2.95 (d, 1H, J ¼ 18.7 Hz,
H-9ax), 2.30 (d, 1H, J ¼ 14.4 Hz, H-30eq), 2.15 (d, J ¼ 3.1 Hz, 1H, H-
30ax), 2.06e2.13 (m, 2H, O]CeCH2), 1.82 (dd, 1H, J ¼ 13.3 Hz,
J ¼ 5.1 Hz, H-7ax), 1.68e1.77 (m, 1H, H-7eq), 1.49e1.55 (m, 2H,
NHCOCH2CH2), 1.25 (d, 3H, J ¼ 6.5 Hz, 60-CH3), 1.23 (br s, 20H,
10 ꢁ CH2, methylene envelope), 0.80e0.88 (m, 3H, Hz, CH3); 13C
NMR (125 MHz, CDCl3,
d ppm): 213.56 (C13]O), 186.68 (C12]O),
186.22 (C5]O), 172.20 (NHeC]O), 160.61 (C1), 155.81 (C6), 155.25
(C11), 135.37 (C3) 135.07 (C10a), 133.25 (C4a), 133.17 (C6a), 120.46
(C12a), 119.46 (C2), 118.00 (C4), 111.16 (C11a), 110.97 (C5a), 100.29
(C20), 76.17 (C8), 69.26 (C60), 69.24 (C50), 66.83 (C10), 65.18 (O]
CeCH2OH), 56.26 (OCH3), 44.60 (NH-C40), 36.40 (NHCOCH2), 35.34
(C30), 33.57 (C9), 29.61 (C7), 31.53, 29.29, 29.25, 29.29, 29.44, 29.08,
28.85, 28.87 (methylene carbons), 25.33 (NHCOCH2CH2), 22.31
(CH2CH3), 16.44 (60-CH3), 13.74 (CH3); HR-MS (ESI-TOF): calcd. for
4.2.1.8. (8S,10S)-10-(4-(N-octadecanoylamido)-5-hydroxy-6-methyl-
tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydrox-
yacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (9). Red
brown solid (65 mg, 87.3% yield). IR (cmꢀ1, ATR): 3346. 2923, 2848,
1716 (C]O),1642(C]O str, amide), 1618, 1575, 1445, 1407, 1373, 1279,
C41H55NO12 753.3724; found, 776.2407 [M þ Na]þ.
.
1233, 1203, 1109, 1068, 1015, 844, 764; UV/vis
l (nm): 478, 290, 254,
234; 1H NMR (500 MHz, CDCl3,
d
ppm): 13.93 (s, 1H, PhOH), 13.18 (s,
4.2.1.6. (8S,10S)-10-(4-(N-(12-thioethyldodecanoylamido))-5-
hydroxy-6-methyl-tetrahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-
8-(2-hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-
dione (7). Red brown solid (66 mg, 91.4% yield). IR (cmꢀ1, ATR):
3346, 2923, 2848, 1716 (C]O), 1642 (C]O str, amide), 1618, 1575,
1445, 1407, 1373, 1279, 1233, 1203, 1109, 1068, 1015, 844, 764; UV/
1H, PhOH), 8.00 (d, J ¼ 7.7 Hz,1H, ArC2H), 7.76 (t,1H, J ¼ 8.1 Hz, ArC3H),
7.37 (d, 1H, J ¼ 8.5 Hz, ArC4H), 7.26 (s,1H, NH), 5.81 (s,1H, OH), 5.48 (br
s,1H, H-20), 5.26 (s,1H, H-50), 4.76 (s, 2H, O]C13eCH2), 4.14e4.19 (m,
2H, H-10 and H-40), 4.06 (s, 3H, OCH3), 3.67 (s, 1H, H-60), 3.24 (d, 1H,
J ¼ 18.6 Hz, H-9eq), 2.94e3.02 (m,1H, H-9ax), 2.32 (d,1H, J ¼ 13.8 Hz,
H-30eq), 2.17 (d,1H, J ¼ 3.8 Hz, H-30ax), 2.10e2.13 (m, 2H, O]CeCH2),
1.87 (dd, 1H, J ¼ 14.2 Hz, J ¼ 6.2 Hz, H-7ax),1.73e1.79 (m, 1H, H-7eq),
1.55 (t, 2H, J ¼ 6.5 Hz, NHCOCH2CH2), 1.28 (d, 3H, J ¼ 6.6 Hz, 60-CH3),
1.25 (br s, 28H, 14 ꢁ CH2, methylene envelope), 0.86e0.89 (m, 3H,
vis
l d ppm):
(nm): 478, 290, 254, 234; 1H NMR (500 MHz, CDCl3,
13.94 (s, 1H, PhOH), 13.20 (s, 1H, PhOH), 8.00 (d, J ¼ 7.6 Hz, 1H,
ArC2H), 779 (t, 1H, J ¼ 7.8 Hz, ArC3H), 7.36 (d, 1H, J ¼ 8.1 Hz, ArC4H),
7.24 (s, 1H, NH), 5.84 (d, 1H, J ¼ 7.4 Hz, OH), 5.50 (s, 1H, H-20), 5.23
(s, 1H, H-50), 4.74 (s, 2H, O]C13eCH2), 4.12e4.15 (m, 2H, H-10 and
H-40), 4.05 (s, 3H, OCH3), 3.60 (s, 1H, H-60), 3.24 (d, 1H, J ¼ 18.1 Hz,
H-9eq), 2.97 (d, 1H, J ¼ 17.7 Hz, H-9ax), 2.47e2.48 (m, 4H, SCH2),
2.30 (d, 1H, J ¼ 14.7 Hz, H-30eq), 2.14e2.19 (m, 1H, H-30a), 2.07e2.12
(m, 2H, O]CeCH2), 1.87 (s, 1H, H-7ax), 1.69e1.75 (m, 1H, H-7eq),
1.56 (br s, 4H, NHCOCH2CH2, SCH2CH2), 1.29 (s merged, 3H, 60-CH3),
1.23 (br s, 14H, 7 ꢁ CH2, methylene envelope), 0.85 (t, 3H, J ¼ 5.9 Hz,
CH3); 13C NMR (125 MHz, CDCl3,
d ppm): 213.94 (C13]O), 186.99
(C12]O),186.55 (C5]O),172.88 (NHeC]O),160.97 (C1),156.21 (C6),
155.58 (C11), 135.74 (C3), 135.43 (C10a), 133.64 (C4a), 133.61 (C6a),
120.78 (C12a), 119.83 (C2), 118.41 (C4), 111.50 (C11a), 111.37 (C5a),
100.64 (C20), 76.49 (C8), 69.60 (C60), 69.56 (C50), 67.25 (C10), 65.55
(O]CeCH2OH), 56.63 (OCH3), 45.12 (NH-C40), 36.75 (NHCOCH2),
35.72 (C30), 33.46 (C9), 29.93 (C7), 31.92, 29.74, 29.70, 29.65, 29.64,
29.63, 29.60, 29.59, 29.48, 29.46, 29.43, 29.36, 29.26, 29.24, 29.06
(methylene carbons), 25.71 (NHCOCH2CH2), 22.69 (CH2CH3), 16.82
(60-CH3), 14.12 (CH3); HR-MS (ESI-TOF): calcd. for C45H63NO12
809.4350; found, 832.2217 [M þ Na]þ.
CH3); 13C NMR (125 MHz, CDCl3,
d ppm): 213.94 (C13]O), 187.10
(C12]O), 186.65 (C5]O), 171.91 (NHeC]O), 161.01 (C1), 156.01
(C6), 155.64 (C11), 135.77 (C3) 135.48 (C10a), 133.61 (C4a), 133.55
(C6a), 120.83 (C12a), 119.86 (C2), 118.41 (C4), 111.57 (C11a), 111.37
(C5a), 100.70 (C20), 76.37 (C8), 69.37 (C60), 69.21 (C50), 66.83 (C10),
65.17 (O]CeCH2OH), 56.27 (OCH3), 43.37 (NH-C40), 36.36
4.2.1.9. (8S,10S)-10-(4-(N-Icosanoylamido)-5-hydroxy-6-methyl-tet-
rahydro-2H-pyran-2-yloxy)-6,8,11-trihydroxy-8-(2-hydroxyacetyl)-