Medicinal Chemistry Research
MHz11.83 (s, 1H, OH), 7.61–7.56 (m, 2H, H-6 and H-8),
7.19–7.17 (m, 1H, H-7), 2.62–2.59 (m, 2H, H-4), 1.83–1.81
(m, 2H, H-3), 1.44 (s, 6H, H-1′) ppm. 13C NMR (CDCl3,
126 MHz): 184.9 (C-10), 183.4 (C-5), 161.6 (C-10a), 154.1
(C-9), 136.5 (C-7), 132.0 (C-5a), 123.5 (C-8), 121.1 (C-9a),
6.4, H-4), 2.12–2.03 (m, 1H, H-3), 1.92–1.79 (m, 2H, H-1′),
1.76–1.47 (m, 3H, H-3 and H-2′), 0.99 (t, 3H, J = 7.2,
H-3′) ppm. 13C NMR (CDCl3, 126 MHz): 184.6 (C-10),
183.5 (C-5), 161.5 (C-10a), 155.0 (C-9), 136.5 (C-7), 132.0
(C-5a), 123.5 (C-8), 122.2 (C-9a), 118.7 (C-6), 114.0
118.7 (C-6), 114.1 (C-4a), 78.4 (C-2), 31.3 (C-4), 26.5
(C-4a), 78.0 (C-2), 36.4 (C-1′), 25.3 (C-4), 18.5 (C-2′), 18.4
(C-3), 13.9 (C-3′) ppm. HRMS: Calcd for C16H16NaO4
295.0941. Found: 295.0935 (M + Na)+.
+
+
(C-1′), 16.8 (C-3) ppm. HRMS: Calcd for C15H15O4
259.0965. Found: 259.0978 (M + H)+.
:
:
9-hydroxy-3-methyl-3,4-dihydro-2H-benzo[g]chromene-
5,10-dione (13b)
Synthesis of β-lapachones (14a, 14c, and 14d)
Into a round bottom flask was added the corresponding
α-lapachones (0.2 mmol) of compounds 14a, 14c, and 14d
and 3 mL of H2SO4. The mixture was left under stirring at
room temperature or with heating in some cases. After the
total consumption of the starting material, observed by
thin layer chromatography, the reaction mixture was
poured into crushed ice and the product was filtered under
vacuum and washed with a small amount of ice water.
Subsequently, the formed solid was transferred to a round
bottom flask and 3 mL of dichloromethane was added.
Finally, the solvent was evaporated under reduced pres-
sure to give the substituted β-lapachones (14a, c, d)
(Watson et al. 2016). All attempts to obtain compound
14b failed.
The α-lapachone (13b) was obtained in quantitative yield as
a yellow solid of mp 160–163 °C. IR (KBr, cm−1): ν 1637,
1609, 1452, 1250, 1192, 1019, 757, 740. 1H NMR (CDCl3,
500 MHz): 11.77 (s, 1H, OH), 7.61–7.56 (m, 2H, H-6 and
H-7), 7.20 (dd, 1H, J = 8.0 and 1.2 Hz, H-8), 4.40–4.37
(m, 1H, H-2), 3.80–3.76 (m, 1H, H-2), 2.82–2.77 (m, 1H,
H-3), 2.14–2.08 (m, 2H, H-4), 1.11–1.09 (m, 3H, H-1′)
ppm. 13C NMR (CDCl3, 126 MHz): 184.6 (C-10), 183.4
(C-5), 161.6 (C-10a), 154.9 (C-9), 136.6 (C-7), 132.0 (C-5a),
123.5 (C-8), 122.1 (C-9a), 118.7 (C-6), 114.0 (C-4a), 74.5
(C-3), 27.2 (C-4), 20.4 (C-1′), 18.4 (C-2) ppm. HRMS: Calcd
−
for C14H11O4 : 243.0663. Found: 243.0655 (M − H)−.
9-hydroxy-2-methyl-3,4-dihydro-2H-benzo[g]chromene-
5,10-dione (13c)
7-hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[h]chromene-
5,6-dione (14a)
The α-lapachone (13c) was obtained in quantitative yield as
a yellow solid of mp 105–109 °C. IR (KBr, cm−1): ν 1636,
1600, 1454, 1267, 1188, 1110, 739. 1H NMR (CDCl3,
500 MHz): 11.81 (s, 1H, OH), 7.61–7.59 (m, 1H, H-6),
7.59–7.56 (m, 1H, H-7), 7.20–7.18 (m, 1H, H-8), 4.34–4.28
(m, 1H, H-2), 2.72 (ddd, 1H, J = 18.9, 5.6 and 3.6 Hz, H-4),
2.51 (ddd, 1H, J = 18.9, 10.1 and 6.4 Hz, H-4), 2.11–2.06
(m, 1H, H-3), 1.73–1.65 (m, 1H, H-3), 1.51 (d, 3H, J =
6.4 Hz, H-1′) ppm. 13C NMR (CDCl3, 75 MHz): 184.6
(C-10), 183.4 (C-5), 161.6 (C-10a), 154.9 (C-9), 136.6
(C-7), 132.0 (C-5a), 123.5 (C-8), 122.1 (C-9a), 118.7 (C-6),
114.0 (C-4a), 74.5 (C-2), 27.2 (C-4), 20.4 (C-1′), 18.4
(C-3) ppm. HRMS: Calcd for C14H12NaO4+: 267.0628.
Found: 267.0629 (M + Na)+.
The β-lapachone (14a) was obtained in quantitative yield,
after 2 h of reaction at room temperature, as a red solid of
mp consistent with the literature (Da Rocha et al. 2011). IR
(KBr, cm−1): ν 3435, 1637, 1586, 1573, 1451, 1400, 1193,
1118, 714. 1H NMR (CDCl3, 300 MHz): 11.97 (s, 1H, OH),
7.53 (dd, 1H, J = 8.5 and 7.6 Hz, H-9), 7.34 (dd, 1H, J =
7.6 and 0.9 Hz, H-10), 7.05 (dd, 1H, J = 8.5 and 0.9 Hz,
H-8), 2.55 (t, 2H, J = 6.6 Hz, H-4), 1.84 (t, 2H, J = 6.6 Hz,
H-3), 1.45 (s, 6H, H-1′) ppm. 13C NMR (CDCl3, 75 MHz):
183.2 (C-6), 178.1 (C-5), 164.3 (C-10b), 161.6 (C-7), 137.9
(C-9), 132.4 (C-10a), 121.5 (C-8), 116.7 (C-10), 113.6
(C-6a), 112.7 (C-4a), 79.2 (C-2), 31.5 (C-4), 26.7 (C-1′),
+
16.1 (C-3) ppm. HRMS: Calcd for C15H14NaO4
:
281.0784. Found: 281.0788 (M + Na)+.
9-hydroxy-2-propyl-3,4-dihydro-2H-benzo[g]chromene-
5,10-dione (13d)
7-hydroxy-2-methyl-3,4-dihydro-2H-benzo[h]chromene-5,6-
dione (14c)
The α-lapachone (13d) was obtained in quantitative yield as
a yellow solid of mp 123–125 °C. IR (KBr, cm−1): ν 1636,
1605, 1262, 1200, 1156, 1119, 1094, 1072, 963, 834, 739,
707. 1H NMR (CDCl3, 500 MHz): 11.82 (s, 1H, OH),
7.62–7.54 (m, 2H, H-7 and H-8), 7.18 (dd, 1H, J = 7.5 and
2.0 Hz, H-6), 4.20–4.12 (m, 1H, H-2), 2.71 (ddd, 1H, J =
18.9, 5.7 and 3,9 Hz, H-4), 2.49 (ddd, 1H, J = 18.9, 9.8 and
The β-lapachone (14c) was obtained in quantitative yield,
after 2 h of reaction at room temperature, as a red solid of
mp 155–160 °C. IR (KBr, cm−1): ν 1630, 1580, 1445, 1401,
1386, 1323, 1186, 1165, 1147, 1115, 1057, 1038, 932, 907,
740, 714, 704. H NMR (CDCl3, 500 MHz): 11.96 (s, 1H),
7.54–7.51 (m, 1H), 7.33 (dd, 1H, J = 7.5, 0.8 Hz), 7.04 (dd,
1