Journal of Natural Products
Article
8
-Bromodehydrosilybin (21). General method A was followed and
temperature. The reaction mixture was heated and stirred at 60 °C for
16 h. The reaction mixture was poured into water and extracted with
EtOAc (3 × 10 mL). The combined organic fractions were washed
with brine, dried over Na SO , and evaporated in vacuo. Unless
otherwise stated the residue was purified by HPLC preparative
chromatography (ASAHIPAK, 5 mL/min isocratic) to give the
corresponding product.
yielded 21 as a yellow solid (35 mg, 30%): HRMS (ESI, m/z) calcd
79
−
for C H O Br [M − H] 557.00888, found 557.00790; HRMS
25
18 10
8
1
(
5
ESI, m/z) calcd for C H O Br [M − H]− 559.00888, found
2
5
18 10
2
4
59.00566.
-Bromosilychristin A (22). General method A was followed and
yielded 22 as a yellow solid (127 mg, 55%): HRMS (ESI, m/z) calcd
6
79
−
for C H O Br [M − H] 559.02453, found 559.02367; HRMS
25
20 10
6,8-Dibromotaxifolin (27). General procedure B was used and
8
1
(
5
ESI, m/z) calcd for C H O Br [M − H]− 561.02453, found
2
5
20 10
afforded 27 as a yellow solid (70 mg, 46%): HRMS (ESI, m/z) calcd
61.02144.
-Bromodehydrosilychristin (23). General method A was followed
79
−
for C H O Br [M − H] 458.87205, found 458.87161; HRMS
1
5
8
7
2
8
81
−
(
ESI, m/z) calcd for C H O Br [M − H] 461.87205, found
1
5
8
7
2
and yielded 23 as a yellow solid (20 mg, 20%). The product was
contaminated with aliphatic impurities (Figure S17, Supporting
Information). Due to the paucity of the starting material, the reaction
462.86710.
6
,8-Dibromoquercetin (28). General procedure B was followed
7
9
and afforded 28 as a yellow solid (75 mg, 50%): HRMS (ESI, m/z)
could not be repeated. HRMS (ESI, m/z) calcd for C H O Br [M
2
5
18 10
79
−
−
calcd for C15
H
6
O
7
Br
2
[M − H] 456.85640, found 456.85593;
−
H] 557.00888, found 557.00812; HRMS (ESI, m/z) calcd for
C H O Br [M − H] 559.00888, found 559.00598.
5
2
residue was purified by FCC (cyclohexane/EtOAc, 40:1) and afforded
4 as a white solid (65 mg, 46%); HRMS (ESI, m/z) calcd for
8
1
[M − H]− 460.85640,
81
18 10
−
HRMS (ESI, m/z) calcd for C15H O Br
6 7 2
2
found 460.85141.
-Bromo-1-naphthol (24). General method A was followed. The
6
,8-Dibromosilybin (29). α,β-Dibromohydrocinnamic acid (924
mg, 3.0 equiv, 3 mmol) and K CO (69 mg, 0.5 equiv, 0.5 mmol)
2
2
3
79
−
were added to a solution of silybin (4) (an equimolar mixture of
silybin diastereomers A and B) (482 mg, 1.0 equiv, 1 mmol) in 15 mL
of dry DMF at room temperature. The reaction mixture was heated
and stirred at 60 °C for 16 h. The reaction mixture was poured into
water and extracted with EtOAc (3 × 30 mL). The combined organic
fractions were washed with brine (3 × 30 mL), dried over Na SO ,
C H O Br [M − H] 220.96075, found: 220.96083; HRMS (ESI,
1
0
7
8
1
−
m/z) calcd for C H O Br [M − H] 222.96075, found 222.95870.
10
7
4
-Bromo-1-naphthylamine (25a) and 2-Bromo-1-naphthyl-
amine (25b). General method A was followed and afforded 25 (46
mg, 44%, isolated as a inseparable mixture of 2- and 4-bromo-1-
naphthylamine): HRMS (ESI, m/z) calcd for C H BrN [M + H]
21.99129, found 221.99114; HRMS (ESI, m/z) calcd for
7
9
+
1
0
9
2
4
2
and evaporated in vacuo. The residue was purified by HPLC
preparative chromatography (ASAHIPAK, MeOH 5 mL/min
isocratic) to give 29 as a yellow oil (302 mg, 47%): HRMS (ESI,
81
+
C H BrN [M + H] 223.99129, found 223.98899.
1
0
9
8
-Bromo-3,7-dihydroxyflavone (26). General method A was
followed and afforded 26 as a white solid (43 mg, 40%): HRMS
79
−
m/z) calcd for C H O Br2 [M − H] 636.93505, found
2
5
19 10
7
9
(
3
3
ESI, m/z) calcd for C H O Br [M + H]+ 332.97570, found:
81
−
1
5
10
4
636.93513; HRMS (ESI, m/z) calcd for C H O Br [M − H]
7
9
+
25 19 10
2
32.97586; HRMS (ESI, m/z) calcd for C H O Br [M + H]
15 10 4
6
40.93505, found 640.93079.
,8-Dibromosilybin A (29a). General procedure B was used and
afforded 29a as a yellow solid (55 mg, 42%): HRMS (ESI, m/z) calcd
34.97570, found 334. 97381.
-Bromo-3,3′,4′,7-tetra-O-methylquercetin (34a) and 6-Bromo-
,3′,4′,7-tetra-O-methylquercetin (34b). General method A was
6
8
3
7
9
−
for C H O Br [M − H] 636.93505, found 636.93445; HRMS
2
5
19 10
2
followed and afforded a mixture of 34a and 34b, ca. 1:1 (HPLC), as a
8
1
−
7
7
9
(ESI, m/z) calcd for C H O Br [M − H] 640.93505, found
2
5
19 10
2
yellow solid (50 mg, 43%): HRMS (ESI, m/z) calcd for C H O Br
1
9
18
+
640.92999.
[
M + H] 437.02304, found 437.02312; HRMS (ESI, m/z) calcd for
C H O Br [M + H] + 439.02304, found 439.02115.
81
6,8-Dibromosilybin B (29b). General procedure B was followed
and afforded 29b as a yellow solid (165 mg, 42%): HRMS (ESI, m/z)
1
9
8
18
7
-Bromo-3,3′,4′,5,7-penta-O-methylquercetin (35). General
7
9
−
calcd for C H O Br [M − H] 636.93505, found 636.93445;
method A was followed and afforded 35 as yellow solid (50 mg,
1%): HRMS (ESI, m/z) calcd for C H O Br [M + H]
51.03869, found 451.03876; HRMS (ESI, m/z) calcd for
C H O Br [M + H] 453.03869, found 453.03676.
0
8
Bromo-3,3′,4′,7-tetra-O-isopropylquercetin (36b). General method
A was followed. The residue was purified by the flash purification
system and afforded 36a as yellow oil (36 mg, 25%) and 36b as a
yellow oil (45 mg, 32%): HRMS (ESI, m/z) calcd for C H O Br
M + H] 549.14824, found 549.1483; HRMS (ESI, m/z) calcd for
25 19 10
2
8
1
−
7
9
+
HRMS (ESI, m/z) calcd for C H O Br [M − H] 640.93505,
4
4
25 19 10
2
2
0
20
7
found 640.92986.
81
+
6,8-Dibromodehydrosilybin (30). General procedure B was
followed and afforded 30 as a yellow solid (40 mg, 30%): HRMS
2
20
7
-Bromo-3,3′,4′,7-tetra-O-isopropylquercetin (36a) and 6-
7
9
−
(ESI, m/z) calcd for C H O Br [M − H] 634.91940, found
2
5
17 10
2
81
−
634.91859; HRMS (ESI, m/z) calcd for C H O Br [M − H]
2
5
17 10
2
6
38.91940, found 638.91461.
6,8-Dibromosilychristin A (31). General procedure B was
employed and afforded 31 as a yellow solid (57 mg, 43%): HRMS
7
7
9
2
7
34
+
[
81
+
C H O Br [M + H] 551.14824, found 551.14647.
79
−
2
7
34
7
(ESI, m/z) calcd for C H O Br [M − H] 636.93505, found
2
5
19 10
2
8
-Bromo-3,3′,4′,5,7-isopropyl-O-methylquercetin (37). General
79
−
6
6
36.93457; HRMS (ESI, m/z) calcd for C H O Br [M − H]
2
5
19 10
2
method A was followed. The residue was purified by FCC (petroleum
ether/EtOAc, 6:1) and afforded 37 as a white solid (45 mg, 40%):
40.93505, found 640.93030.
,4-Dibromo-1-naphthol (32). General procedure B was em-
ployed and afforded 32 as a yellow solid (85 mg, 41%): HRMS (ESI,
2
HRMS (ESI, m/z) calcd for C H O Br [M + H]+ 591.19519,
7
7
9
3
0
40
81
7
found 591.19545; HRMS (ESI, m/z) calcd for C H O Br [M +
79
−
3
0
40
m/z) calcd for C H Br O [M − H] 298.87126, found 298.87132;
+
10
6
2
H] 593.19519, found 593.19351.
-Bromo-7-O-methylsilybin (38). General method A was followed
and afforded 39 as a white solid (31 mg, 30%, containing 20% of the
8
1
−
HRMS (ESI, m/z) calcd for C H Br O [M − H] 302.87126,
1
0
6
2
6
found 302.86699.
7
9
2,4-Dibromo-1-naphthylamine (33). General procedure B was
followed and afforded 33 as a yellow solid (92 mg, 44%): HRMS
8
−
-bromo derivative): HRMS (ESI, m/z) calcd for C H O Br [M
H] 573.04018, found 573.04049; HRMS (ESI, m/z) calcd for
26 22 10
−
7
9
+
81
22 10
−
(ESI, m/z) calcd for C H Br N [M + H] 299.90180, found
10 8 2
C H O Br [M − H] 575.04018, measured 573.03866.
2
6
8
1
+
2
2
99.90140; HRMS (ESI, m/z) calcd for C H Br N [M + H]
10 8 2
6
-Bromo-7-O-benzylsilybin (39). General method A was followed
99.90180, found 299.89685.
and afforded 39 as a white solid (50 mg, 44%, containing 20% of the
-bromo derivative): HRMS (ESI, m/z) calcd for C H O Br [M
7
9
6,8-Dibromo-3,3′,4′,7-tetra-O-isopropylquercetin (40). General
8
−
32 26 10
−
method B was followed. The residue was purified by FCC (6:1
petroleum ether/EtOAc) and afforded 40 as a white solid (70 mg,
H] 649.07148, found 649.07055; HRMS (ESI, m/z) calcd for
79
26 10
−
C H O Br [M − H] 651.07148, found 649.06724.
3
2
7
9
[M + H]+
General Method B for Dibromination. α,β-Dibromohydrocin-
namic acid (3.0 equiv) and K CO (0.5 equiv) were added to a
46%): HRMS (ESI, m/z) calcd for for C27H O Br
627.05875, found 627.05914. C27
33 7 2
8
1
+
H O Br [M + H] 631.05875,
33 7 2
2
3
solution of starting material (1.0 equiv) in dry DMF at room
found 631.05475.
G
J. Nat. Prod. XXXX, XXX, XXX−XXX