1
natural product HA . These results encourage us to discover the novel anticancer agents from natural product. The follow-up studies on
mechanism of action and pharmacokinetics of candidate derivatives 6a are in progress and the results will be reported in due time.
Acknowledgements
This work was supported by the Education Department of Jiangxi Province on Science and Technology Project Foundation
GJJ150842) and Doctoral Scientific Research Foundation of Jiangxi University of Traditional Chinese Medicine (2015BS012).
(
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2. Typical synthetic procedure of 4: To a solution of compound 3 (0.3 g, 0.82 mmol) in THF (3 mL) was added diol (3 mmol) and 25% NaOH aq. (0.15
mL, 0.9 mmol) respectively. The reaction was stirred at room temperature for 3 h. Then the mixture was extracted by ethyl acetate (25 mL × 2). The
4
organic phase was combined, washed with saturated brine (15 mL × 2), dried over anhydrous MgSO and filtered. The filtrate was evaporated to give
crude product, which was purified by column chromatography (petroleum ether: ethyl acetate = 2: 1) to give compounds 4a-4d. Compound 4a as white
1
solid, 92% yield. H-NMR (600 MHz, CDCl
.16-2.12 (m, 2H), 1.91 (s, 1H); MS-ESI: [M+Na] : 323.2.
2 2 4
3. Typical synthetic procedure of 5: To a solution of compound 4 (0.83 mmol) in CH Cl (3 mL) was added CBr (0.3 g, 0.92 mmol) at 0 ℃. The mixture
3
) δ (ppm): 8.07-8.05 (m, 2H), 7.78-7.75 (m, 1H), 7.67-7.61 (m, 2H), 4.60 (t, J=6.0, 2H), 3.89 (s, 2H),
+
2
3
3
of PPh (0.24 g, 0.92 mmol) in CH Cl (1.5 mL) was added dropwise under N at 0 ℃. The reaction was stirred at room temperature for overnight.
Then the solution was diluted by CH Cl . The organic phase was washed with saturated brine (15 mL × 2), dried over anhydrous MgSO and filtered.
The filtrate was evaporated to give crude product, which was purified by column chromatography (petroleum ether: ethyl acetate = 4: 1) to give
3
2
2
2
2
2
4
1
3
compounds 5a-5d. Compound 5a as white solid, 78 yield. H-NMR (600 MHz, CDCl ) δ (ppm): 8.09-8.07 (m, 2H), 7.80 (m, 1H), 7.67-7.66 (m, 2H),
-
.61 (m, 2H), 3.62 (m, 2H), 2.43 (m, 2H); MS-ESI: [M-H] : 361.8.
4
1
4. Compound 6a as white solid, 78% yield. H-NMR (600 MHz, CD
3
OD) δ (ppm): 8.07 (d, J=7.7 Hz, 2H, SO
2
Ph), 7.87 (t, J=7.4 Hz, 1H, SO
CH CH -), 4.52-4.49 (m, 1H, -CH
-), 2.27-2.24 (m, 2H, -CH CH CH -), 1.25 (d, J=6.2 Hz,
), 0.82 (s, 3H, CH ), 0.64 (s, 3H, CH ), 0.36 (s, 3H, CH
OD) δ: 177.6, 159.2, 144.0, 138.1, 136.1, 130.0 (× 2), 128.4 (× 2), 122.4, 110.6, 104.9, 104.0, 100.6, 88.7, 78.3, 76.9, 76.6, 75.7,
4.0, 72.6, 72.4, 70.8, 70.7, 70.1, 68.8, 67.8, 63.3, 61.4, 60.0, 55.6, 46.8, 45.8, 41.4, 41.3, 39.2, 38.9, 38.8, 38.5, 36.5, 33.4, 32.5, 32.4, 32.3, 30.4, 27.6,
2
Ph), 7.74 (t,
II
J=7.9 Hz, 2H, SO Ph), 5.25 (t, J=3.2 Hz, 1H, H-12), 5.20 (d, J=1.2 Hz, 1H, H-1 ), 4.58-4.55 (m, 1H, -CH
2
2
2
2
2
CH CH
2
2
-
III
I
)
, 4.47 (d, J=5.4 Hz, 1H, H-1 ), 4.45 (d, J=7.7 Hz, 1H, H-1 ), 4.27-4.20 (m, 2H, -CH
2
CH
2
CH
2
2
2
2
II
13
3
H, H-6 ), 1.13 (s, 3H, CH
3
), 1.02 (s, 3H, CH
3
), 0.95 (s, 3H, CH
3
), 0.92 (s, 3H, CH
3
3
3
3
); C-
NMR (150 MHz, CD
3
7
2
1
+
7.4, 27.3, 25.9, 25.3, 23.1, 22.9, 22.7, 17.9, 17.1, 16.4, 16.1, 14.6; HRMS-ESI (M+Na) m/z calcd. for C58
201.5380.
H
86
N
2
NaO21S, 1201.5341, found,
1
3
5. Compound 6b as white solid, 80% yield. H-NMR (600 MHz, CD
3
OD) δ (ppm): 8.05-8.04 (m, 2H, SO
2
Ph), 7.85-7.83 (m, 1H, SO
CH CH -), 4.45 (d, J=5.4 Hz, 1H, H-1 ), 4.42
-), 1.86-1.78 (m, 2H, -CH CH CH CH -), 1.21 (d,
), 0.88 (s, 3H, CH ), 0.82 (s, 3H, CH ), 0.71 (s, 3H,
OD) δ: 179.6, 160.6, 145.2, 139.8, 137.1, 131.2 (× 2), 129.7 (× 2), 124.1, 111.9, 106.0, 105.3, 102.2, 90.6, 79.1, 78.2,
8.0, 77.3, 75.5, 74.1, 73.5, 72.4, 72.3, 71.5, 70.3, 65.2, 64.4, 62.8, 57.2, 49.6, 48.3, 47.2, 43.0, 42.9, 40.8, 40.4, 40.1, 38.0, 34.9, 34.1, 33.9, 33.6, 31.8,
2
Ph), 7.71-7.69 (m,
II
III
2
H, SO
2
Ph), 5.25 (t, J=3.4 Hz, 1H, H-12), 5.16 (d, J=1.3 Hz, 1H, H-1 ), 4.48 (t, J=6.4 Hz, 2H,-CH
2
CH
2
2
2
I
(
d, J=7.7 Hz, 1H, H-1 ), 4.15-4.06 (m, 2H, -CH
2
CH
2
CH
2
CH
2
-), 1.98-1.94 (m, 2H, -CH
2
CH
2
CH
2
CH
2
2
2
2
2
II
J=6.2 Hz, 3H, H-6 ), 1.14 (s, 3H, CH
3
), 1.00 (s, 3H, CH
3
), 0.91 (s, 3H, CH
3
), 0.90 (s, 3H, CH
3
3
3
1
3
3 3
CH ); C-NMR (150 MHz, CD
7
3
+
88 2
0.3, 28.9, 28.8, 27.2, 26.6, 26.5, 26.2, 24.7, 24.2, 24.1, 19.4, 18.1, 18.0, 17.2, 16.1; HRMS-ESI (M+Na) m/z calcd. for C59H N O21NaS, 1215.5498,
found, 1215.5613.
6. Compound 6c as white solid, 76% yield. H-NMR (600 MHz, CD
1
3
3
OD) δ (ppm): 8.10-8.05 (m, 2H, SO
Ph), 5.25 (s, 1H, H-12), 5.20 (s, 1H, H-1 ), 5.16-5.14 (m, 1H, -CH(CH )CH CH -), 4.49 (m, 1H, -CH(CH
-), 2.26-2.19 (m, 1H, -CH(CH )CH CH -), 2.13-2.09 (m, 1H, -CH(CH
), 1.03 (s, 3H, CH ), 0.94 (s, 3H, CH ), 0.93 (s, 3H, CH
2
Ph), 7.88-7.86 (m, 1H, SO
2
Ph), 7.77-7.72 (m,
II
2
H, SO
III
2
3
2
2
3
)CH CH -), 4.47 (d, J=5.4 Hz, 1H,
2
2
I
H-1 ), 4.45 (d, J=7.7 Hz, 1H, H-1 ), 4.40 (m, 1H, -CH(CH
3
)CH
2
CH
2
3
2
2
3
)CH
2
CH
2
-),
II
1
0
1
.33 (d, J=2.5 Hz, 3H, -CH(CH
.92 (s, 3H, CH ), 0.83 (s, 3H, CH
23.9, 112.0, 106.0, 105.3, 102.1, 90.6, 79.1, 78.2, 78.0, 77.2, 75.5, 74.1, 73.6, 72.2, 71.5, 70.3, 68.8, 68.1, 64.4, 62.8, 61.6, 57.1, 49.7, 48.2, 47.3, 42.9,
3
)CH
2
CH
2
-), 1.25 (d, J=6.2 Hz, 3H, H-6 ), 1.14 (s, 3H, CH
3
3
3
3
),
1
3
3
3
), 0.66 (s, 3H, CH
3 3
); C-NMR (150 MHz, CD OD) δ: 178.8, 160.7, 145.3, 139.6, 137.2, 131.3 (× 2), 129.9 (× 2),