1214
X.-R. Cui et al. / European Journal of Medicinal Chemistry 43 (2008) 1206e1215
The filtrate was evaporated to give a residue which was
subjected to preparative HPLC (column: ODS-4251-D,
10 ꢁ 250 mm; solvent system: H2OeCH3COCH3eAcOH
(225:271:4); flow rate: 1.0 ml/min; column temperature:
40 ꢂC) to obtain 1,8-O-dipropionylphyscion (8, 180 mg) and
1,8-O-dipropionylchrysophanol (9, 70 mg). Compound 8:
EIMS: m/z 396 [M]þ; 1H NMR (CDCl3) d 7.99 (1H, dd,
J ¼ 1.8, 0.6 Hz, H-5), 7.66 (1H, d, J ¼ 2.7 Hz, H-4), 7.18
(1H, dd, J ¼ 1.8, 0.6 Hz, H-7), 6.86 (1H, d, J ¼ 2.7 Hz, H-2),
3.95 (3H, s, OCH3), 2.74 (2H, q, J ¼ 7.6 Hz, COCH2CH3),
2.73 (2H, q, J ¼ 7.6 Hz, COCH2CH3), 2.48 (3H, s, 3-CH3),
1.34 (6H, t, J ¼ 7.6 Hz, COCH2CH3 ꢁ 2); 13C NMR (CDCl3)
d 182.3 (C-10), 179.5 (C-9), 172.8 and 172.6 (COCH2CH3 ꢁ
2), 163.9 (C-6), 152.4 (C-8), 150.3 (C-1), 145.6 (C-3), 136.0
(C-11), 134.2 (C-14), 130.8 (C-4), 125.8 (C-13), 123.3 (C-2),
119.4 (C-12), 116.4 (C-5), 116.4 (C-7), 56.1 (6-OCH3), 27.7
(COCH2CH3 ꢁ 2), 21.6 (C-15), 8.7 (COCH2CH3 ꢁ 2). Anal.
Calcd for C22H20O7: C, 66.66; H, 5.09. Found: C, 66.53; H,
12.56 (each 1H, s, 5 and 8-OH), 7.18 (2H, s, H-6 and 7),
6.98 (1H, d, J ¼ 0.9 Hz, H-3), 6.02 (1H, ddd, J ¼ 7.3, 4.6,
0.9 Hz, H-11), 5.13 (1H, br t, J ¼ 7.3 Hz, H-13), 2.48 (1H,
m, H-20), 1.69 (3H, s, 15-CH3), 1.59 (3H, s, 16-CH3), 1.22
(3H, d, J ¼ 7.0 Hz, 30-CH3), 1.21 (3H, d, J ¼ 7.0 Hz, 40-
CH3). The 13C NMR signals are listed in Table 3.
5.1.1.12. 30-Hydroxyisovalerylshikonin (14). EIMS: m/z 388
1
(Mþ); H NMR (CDCl3) d 12.60 and 12.40 (each 1H, s, 5-
and 8-OH), 7.20 (2H, s, H-6 and 7), 7.03 (1H, d, J ¼ 1.0 Hz,
H-3), 6.09 (1H, ddd, J ¼ 7.6, 4.6, 1.0 Hz, H-11), 5.12 (1H,
br t, J ¼ 7.6 Hz, H-13), 2.63 (1H, m, H-120a), 2.49 (1H, dt,
J ¼ 15.3, 7.6 Hz, H-2b0), 1.69 (3H, d, J ¼ 0.9 Hz, 15-CH3),
1.59 (3H, d, J ¼ 0.9 Hz, 16-CH3), 1.31 (3H, s, 40-CH3), 1.30
(3H, s, 50-CH3). The 13C NMR signals are listed in Table 3.
5.1.1.13. Acetylshikonin (16) and acetylalkannin (19). EIMS:
1
m/z 330 [M]þ; H NMR (CDCl3) d 12.60 and 12.40 (each
1
4.95. Compound 9: EIMS: m/z 366 [M]þ; H NMR (CDCl3)
1H, s, 5- and 8-OH), 7.18 (2H, s, H-6 and 7), 6.99 (1H, s,
H-3), 6.02 (1H, ddd, J ¼ 7.4, 4.6, 0.9 Hz, H-11), 5.12 (1H,
br t, J ¼ 7.6 Hz, H-13), 2.62 (1H, br dt, J ¼ 15.0, 7.3 Hz,
H-120a), 2.48 (1H, dt, J ¼ 15.0, 7.3 Hz, H-2b0), 2.14 (3H, s,
COCH3), 1.69 (3H, s, 15-CH3), 1.57 (3H, s, 16-CH3). The
13C NMR signals are listed in Table 3.
d 8.19 (1H, dd, J ¼ 7.6, 1.2 Hz, H-5), 8.00 (1H, dd, J ¼ 1.8,
0.6 Hz, H-4), 7.73 (1H, t, J ¼ 7.9 Hz, H-6), 7.20 (1H, dd,
J ¼ 1.8, 0.6 Hz, H-2), 2.74 (2H, q, J ¼ 7.6 Hz, COCH2CH3),
2.73 (2H, q, J ¼ 7.6 Hz, COCH2CH3), 2.49 (3H, s, 3-CH3),
1.35 (3H, t, J ¼ 7.6 Hz, COCH2CH3), 1.34 (3H, t, J ¼ 7.6 Hz,
COCH2CH3); 13C NMR (CDCl3) d 182.3 and 180.5 (C-9 an
C-10), 172.8 (COCH2CH3), 172.8 (COCH2CH3), 150.3 (C-8),
150.2 (C-1), 146.2 (C-3), 134.6 (C-6), 134.3 (C-11), 134.2
(C-14), 130.7 (C-12), 130.2 (C-4), 125.8 (C-5), 125.8 (C-7),
125.3 (C-13), 123.4 (C-2), 27.8 (COCH2CH3 ꢁ 2), 21.7
(C-15), 8.8 (COCH2CH3 ꢁ 2). Anal. Calcd for C21H18O6: C,
68.85; H, 4.95. Found: C, 66.52; H, 5.06.
1
5.1.1.14. Ethylshikonin (21). EIMS: m/z 316 [M]þ; H NMR
(CDCl3) d 12.60 and 12.51 (each 1H, s, 5- and 8-OH), 7.26
(2H, s, H-6 and 7), 7.20 (1H, s, H-2), 5.20 (1H, dt, J ¼ 7.6,
1.2 Hz, H-13), 4.66 (1H, ddd, J ¼ 7.0, 4.2, 0.9 Hz, H-11),
4.48 (1H, dq, J ¼ 13.7, 7.0 Hz, H-10a), 4.46 (1H, dq,
J ¼ 13.7, 7.0 Hz, H-10b), 2.52 (1H, m, H-120a), 2.30 (1H, dt,
J ¼ 15.0, 7.0 Hz, H-12b0), 1.70 (3H, s, 15-CH3), 1.60 (3H, s,
5.1.1.9. Physcion (2). A solution of compound 8 (150 mg) in
1.0 M KOH (5 ml, MeOHeH2O ¼ 1:1) was stirred for 7 h at
room temperature. The reaction mixture was poured into H2O
(20 ml) and then extracted with AcOEt (20 ml ꢁ 2). The
organic extracts were successively washed with 5% HCl,
10% NaHCO3 and H2O, then dried over absolute MgSO4 and
filtered. The filtrate was evaporated to give a residue which
was subjected to column chromatography to obtain physcion
Table 3
13C NMR spectral data of hydroxynaphthoquinones 13, 14, 16, 19, 22, 21 and
23 in CDCl3
13 and 22
14
16 and 19
21
23
C-1
C-2
176.8
135.9
148.5
178.3
167.3
132.7a
132.6a
166.7
111.5b
111.8b
69.0
175.4
136.4
147.5
177.0
168.7
133.3a
133.1a
168.1
111.6b
111.8b
69.8
176.7
136.7
148.2
178.2
167.5
132.9a
132.7a
167.0
111.6b
111.8b
69.5
176.2
134.7
151.0
179.9
166.2
132.4a
132.3a
165.7
111.6b
112.0b
65.4
176.7
131.6
148.6
178.0
167.0
136.0
136.0
167.5
112.0
112.0
68.7
1
(2, 90 mg, 83.3%). EIMS: m/z 284 [M]þ; H NMR (CDCl3)
C-3
C-4
d 12.31 and 12.11 (each 1H, s, 1- and 8-OH), 7.62 (1H, d,
J ¼ 1.2 Hz, H-5), 7.36 (1H, d, J ¼ 2.4 Hz, H-4), 7.07 (1H, dd,
J ¼ 1.5, 0.9 Hz, H-7), 6.68 (1H, d, J ¼ 2.4 Hz, H-2), 3.94
(3H, s, OCH3), 2.45 (3H, s, CH3); 13C NMR (CDCl3) d 190.8
(C-9), 182.0 (C-10), 166.5 (C-3), 165.2 (C-1), 162.5 (C-8),
145.4 (C-6), 135.2 (C-14), 133.2 (C-11), 124.5 (C-7), 121.3
(C-5), 113.7 (C-12), 110.2 (C-13), 108.2 (C-4), 106.8 (C-2),
56.1 (OCH3), 22.2 (C-15).
C-5
C-6
C-7
C-8
C-9
C-10
C-11
C-12
C-13
C-14
C-15
C-16
C-10
C-20
C-30
C-40
C-50
32.9
32.9
32.8
34.4
33.0
117.8
131.3
25.7
117.7
131.3
25.8
117.7
131.5
25.8
119.1
132.1
26.5
117.9
136.0
25.7
5.1.1.10. Isolation of hydroxynaphthoquinone derivatives. Hy-
droxynaphthoquinone derivatives were isolated according to
the procedure described in this text and the scheme shown
in Fig. 5.
18.9
17.0
171.7
46.5
17.9
169.8
21.0
17.9
65.3
17.9
175.7
34.0
17.9
171.8
25.1
43.2
15.3
e
e
69.2
e
e
18.8
e
29.2c
29.1c
22.4
e
e
e
5.1.1.11. Isobutylshikonin (13) and isobutylalkannin
1
(22). EIMS: m/z 358 [M]þ; H NMR (CDCl3) d 12.58 and
a,b,c: These values may be interchangeable in each column.