C.-X. Gu, J.-G. Liu, W.-W. Chen et al.
Tetrahedron 85 (2021) 132048
119.2, 116.0, 112.7, 106.6, 99.4, 97.2, 56.2, 56.0. HRMS (ESI): calcd for
C
d
ꢁ114.38 ~ ꢁ114.40 (m). HRMS (ESI): Calcd for C15H8FO3 [MþH]þ:
17H13O5 [MþH]þ: 297.0758, found: 297.0756.
255.0452, found 255.0453.
4.2.13. 1,3,8-trimethoxy-11H-benzofuro[2,3-b]chromen-11-one
(2m)
4.2.19. 2-fluoro-9-methoxy-11H-benzofuro[2,3-b]chromen-11-one
(2s)
White solid, Method A: 26.1 mg, 40% yield, Method B: 28.8 mg,
White solid, Method A: 30.1 mg, 53% yield, Method B: 45.4 mg,
44% yield. 1H NMR (600 MHz, CDCl3)
d
8.04 (d, J ¼ 8.5 Hz, 1H), 7.07
(s, 1H), 7.01 (d, J ¼ 8.6 Hz, 1H), 6.63 (s, 1H), 6.47 (s, 1H), 3.99 (s, 3H),
3.92 (s, 3H), 3.87 (s, 3H). 13C NMR (150 MHz, CDCl3)
173.8, 163.6,
80% yield. 1H NMR (600 MHz, CDCl3)
d
8.04 (dd, J ¼ 8.2, 3.1 Hz, 1H),
7.66 (d, J ¼ 2.7 Hz, 1H), 7.62 (dd, J ¼ 9.1, 4.1 Hz, 1H), 7.47e7.42 (m,
d
2H), 6.96 (dd, J ¼ 9.0, 2.7 Hz, 1H), 3.91 (s, 3H). 13C NMR (150 MHz,
163.4, 161.9, 158.3, 157.2, 150.3, 122.2, 116.8, 112.6, 109.0, 99.9, 97.1,
96.9, 93.7, 56.6, 56.02, 55.98. HRMS (ESI): calcd for C18H15O6
[MþH]þ: 327.0863, found: 327.0862.
CDCl3)
d
173.0,165.7,160.1 (d, J ¼ 246.0 Hz),157.9,149.3,143.9,125.6
(d, J ¼ 6.9 Hz), 123.5, 121.4 (d, J ¼ 25.1 Hz), 119.9 (d, J ¼ 8.1 Hz), 114.1,
112.1, 112.0 (d, J ¼ 8.0 Hz), 104.9, 99.8, 58.2. 19F NMR (564 MHz,
CDCl3):
d
ꢁ114.46
~
ꢁ114.46 (m). HRMS (ESI): Calcd for
4.2.14. 2-fluoro-11H-benzofuro[2,3-b]chromen-11-one (2n)
C
16H10FO4[MþH]þ: 285.0558, found 285.0559.
White solid, Method A: 30.1 mg, 53% yield, Method B: 36.9 mg,
65% yield. 1H NMR (400 MHz, CDCl3)
d
7.84 (d, J ¼ 5.9 Hz, 1H), 7.74
(d, J ¼ 2.5 Hz, 1H), 7.52 (d, J ¼ 9.1 Hz, 1H), 7.47 (dd, J ¼ 8.8, 3.6 Hz,
1H), 7.29 (dd, J ¼ 9.2, 2.9 Hz, 1H), 7.09 (dd, J ¼ 8.9, 6.8 Hz, 1H), 3.93
4.2.20. 2-fluoro-9-(trifluoromethyl)-11H-benzofuro[2,3-b]
chromen-11-one (2t)
(s, 3H). 13C NMR (125 MHz, CDCl3)
d
173.6, 165.9, 160.5 (d, J ¼
White solid, Method A: 30.2 mg, 47% yield, Method B: 12.9 mg,
20% yield. 1H NMR (600 MHz, CDCl3)
d
8.49 (s, 1H), 8.06 (dd, J ¼ 8.1,
240.0 Hz), 157.6, 147.8, 145.4, 124.7, 124.3 (d, J ¼ 11.3 Hz), 122.9,
119.2, 112.8 (d, J ¼ 26.3 Hz), 112.2 (d, J ¼ 8.8 Hz), 108.6 (d, J ¼
26.3 Hz),106.8, 99.4, 56.2. HRMS (ESI): Calcd for C16H10FO4[MþH]þ:
285.0558, found 285.0559.
3.1 Hz, 1H), 7.72e7.68 (m, 2H), 7.66 (dd, J ¼ 4.5 Hz, 4.5 Hz, 1H), 7.49
(ddd, J ¼ 9.1, 7.3, 3.1 Hz, 1H). 13C NMR (150 MHz, CDCl3)
d 172.7,
166.1, 160.3 (d, J ¼ 246.9 Hz), 150.8, 149.4, 128.4 (q, 2JCF ¼ 32.6 Hz),
1
125.6 (d, J ¼ 7.4 Hz), 124.3 (q, JCF ¼ 270.1 Hz), 123.3, 123.1 (q,
3JCF ¼ 3.1 Hz), 121.8 (d, J ¼ 25.2 Hz), 120.1 (d, J ¼ 8.0 Hz), 119.8 (q,
4.2.15. 9-chloro-2-methoxy-11H-benzofuro[2,3-b]chromen-11-one
(2o)
3JCF ¼ 3.8 Hz), 112.3 (d, J ¼ 24.6 Hz), 111.9, 99.2. 19F NMR (564 MHz,
White solid, Method A: 24.6 mg, 41% yield, Method B: 33.1 mg,
CDCl3):
C
d
ꢁ61.33 (s), ꢁ113.63 ~ ꢁ113.67 (m). HRMS (ESI): Calcd for
55% yield. 1H NMR (600 MHz, CDCl3)
d 8.17 (s, 1H), 7.76 (d,
16H7F4O3 [MþH]þ: 323.0326, found 323.0327.
J ¼ 2.8 Hz,1H), 7.54 (d, J ¼ 9.1 Hz,1H), 7.46 (d, J ¼ 8.7 Hz,1H), 7.35 (d,
J ¼ 8.7 Hz, 1H), 7.31 (dd, J ¼ 9.0, 2.8 Hz, 1H), 3.95 (s, 3H). 13C NMR
4.2.21. 2-fluoro-7-methyl-11H-benzofuro[2,3-b]chromen-11-one
(2u)
(150 MHz, CDCl3) d 173.6, 165.7, 157.7, 147.9, 147.7, 131.1, 125.6, 124.7,
124.5, 123.0, 121.9, 119.3, 112.3, 106.8, 98.9, 56.2. HRMS (ESI): calcd
for C16H10ClO4 [MþH]þ: 301.0262, found: 301.0264.
White solid, Method A: 34.3 mg, 64% yield, Method B: 41.3 mg,
77% yield. 1H NMR (600 MHz, CDCl3)
d
8.04 (dd, J ¼ 8.2, 3.1 Hz, 1H),
7.99 (d, J ¼ 7.5 Hz, 1H), 7.62 (dd, J ¼ 9.1, 4.1 Hz, 1H), 7.46e7.42 (m,
4.2.16. 2,9-dimethoxy-11H-benzofuro[2,3-b]chromen-11-one (2p)
1H), 7.33 (dd, J ¼ 7.6, 7.6 Hz, 1H), 7.21 (d, J ¼ 7.5 Hz, 1H), 2.56 (s, 3H).
White solid, Method A: 42.6 mg, 72% yield, Method B: 34.9 mg,
13C NMR (150 MHz, CDCl3)
d
173.0 (d, J ¼ 1.5 Hz), 165.3, 160.1 (d, J ¼
59% yield. 1H NMR (400 MHz, CDCl3)
d
7.71 (d, J ¼ 2.7 Hz, 1H), 7.62
246.0 Hz), 149.3, 148.5, 127.1, 125.7 (d, J ¼ 7.1 Hz), 125.5, 122.3, 121.6,
121.3 (d, J ¼ 25.4 Hz), 119.9 (d, J ¼ 8.4 Hz), 119.6, 112.1 (d, J ¼
(d, J ¼ 2.1 Hz,1H), 7.48 (d, J ¼ 9.1 Hz,1H), 7.37 (d, J ¼ 9.0 Hz,1H), 7.24
(dd, J ¼ 9.1, 2.9 Hz, 1H), 6.90 (dd, J ¼ 8.9, 2.3 Hz, 1H), 3.92 (s, 3H),
24.5 Hz), 99.7, 15.0. 19F NMR (564 MHz, CDCl3):
d
ꢁ114.51 ~ ꢁ114.54
3.90 (s, 3H). 13C NMR (125 MHz, CDCl3)
d 173.7, 165.5, 157.6, 157.4,
(m). HRMS (ESI): Calcd for C16H10FO3 [MþH]þ: 269.0608, found
147.7, 143.8, 124.7, 123.7, 122.5, 119.1, 113.5, 111.8, 106.7, 104.9, 99.5,
56.11, 56.06. HRMS (ESI): Calcd for C17H13O5 [MþH]þ: 297.0757,
found 297.0759.
269.0609.
4.3. General procedures for the synthesis of natural product
Lupinalbin A
4.2.17. methyl(S)-2-(1,3-dioxoisoindolin-2-yl)-3-(2-methoxy-11-
oxo-11H-benzofuro[2,3-b]chromen-9-yl) propanoate (2q)
White solid, Method A: 33.8 mg, 34% yield, Method B: 44.8 mg,
A solution of CDC product 2m (32.6 g, 0.1 mmol) in 2 mL DCM
was cooled to 0 ꢀC and was treated with boron tribromide (2 mL,
1M in DCM). The reaction mixture was stirred at 45 ꢀC for 24 h.
Then the reaction mixture was cooled to room temperature and
quenched with NaHCO3 (aq.) (10 mL). After extracted with EtOAc
(30 mL✕3), the combined organic phases were dried by anhydrous
Na2SO4 and concentrated. The product Lupinalbin A was isolated by
flash chromatograph (petroleum ether/ethyl acetate ¼ 4/1) as
white solid (15.3 mg, 54% yield).
45% yield. 1H NMR (600 MHz, CDCl3)
d 8.04 (s, 1H), 7.84e7.72 (m,
3H), 7.70e7.63 (m, 2H), 7.51 (d, J ¼ 9.0 Hz, 1H), 7.35 (d, J ¼ 8.4 Hz,
1H), 7.28 (d, J ¼ 2.1 Hz, 1H), 7.17 (d, J ¼ 8.4 Hz, 1H), 5.22 (dd, J ¼ 11.5,
4.8 Hz, 1H), 3.94 (s, 3H), 3.81 (s, 3H), 3.77 (dd, J ¼ 14.5, 4.6 Hz, 1H),
3.72e3.64 (m, 1H). 13C NMR (150 MHz, CDCl3)
d 173.7, 169.3, 167.6,
165.5, 157.5, 148.4, 147.8, 134.29, 134.26, 131.7, 126.1, 124.8, 123.7,
123.5, 122.7, 122.5, 119.2, 111.2, 106.8, 99.2, 56.2, 53.9, 53.1, 34.8.
HRMS (ESI): Calcd for
498.1184.
C
28H20NO8 [MþH]þ: 498.1184, found:
4.2.18. 2-fluoro-11H-benzofuro[2,3-b]chromen-11-one (2r)
4.3.1. 1,3,8-trimethoxy-11H-benzofuro[2,3-b]chromen-11-one
(Lupinalbin A)
White solid, Method A: 30.0 mg, 59% yield, Method B: 40.1 mg,
79% yield. 1H NMR (600 MHz, CDCl3)
d
8.19 (d, J ¼ 8.6 Hz, 1H), 8.05
(dd, J ¼ 8.2, 3.1 Hz, 1H), 7.64 (dd, J ¼ 9.1, 4.1 Hz, 1H), 7.56 (d, J ¼
7.7 Hz, 1H), 7.48e7.40 (m, 3H). 13C NMR (150 MHz, CDCl3)
173.0,
White solid, 15.3 mg, 54% yield. 1H NMR (600 MHz, Acetone-d6)
d
12.98 (s,1H), 9.51 (br,1H), 8.95 (br,1H), 7.81 (d, J ¼ 8.3 Hz,1H), 7.13
d
(s, 1H), 7.02 (d, J ¼ 8.3 Hz, 1H), 6.59 (s, 1H), 6.37 (s, 1H). 13C NMR
165.5, 160.2 (d, J ¼ 246.0 Hz), 149.4 (d, J ¼ 22.7 Hz), 125.8, 125.7 (d,
(150 MHz, Acetone-d6) d179.6, 165.7, 164.3, 164.0, 157.2, 156.1, 151.4,
J ¼ 7.4 Hz),125.6,122.8,122.2,121.5,121.3,120.0 (d, J ¼ 8.0 Hz),112.1
122.3, 115.2, 114.6, 104.5, 100.7, 99.6, 98.4, 95.6. HRMS (ESI): Calcd
(d,
J
¼
24.0 Hz), 111.4, 99.5. 19F NMR (564 MHz, CDCl3):
for C15H9O6 [MþH]þ: 285.0394, found: 285.0391.
6