7
8
A. Idhayadhulla et al. / Bioorganic Chemistry 52 (2014) 77–82
2
.2.2.3. Methyl 6-hydroxy-2-phenyl-4H-benzo[h]chromene-5-carbox-
1
ylate (7). Brown solid, 2.92 g, 88% yield, Mp 108–109 °C; H NMR
(
(
1
300 MHz, CDCl
d, J = 8.4 Hz, 1H), 7.74 (d, J = 7.2 Hz, 2H), 7.65 (dd, J = 8.4, 7.2 Hz,
H), 7.48 (dd, J = 8.4, 7.2 Hz, 1H), 7.44–7.32 (m, 3H), 5.49 (t,
3
) d 12.49 (s, 1H),), 8.36 (d, J = 8.4 Hz, 1H), 8.24
13
J = 3.9 Hz, 1H), 3.93 (s, 3H), 3.83 (d, J = 3.9 Hz, 2H); C NMR
(
3
75 MHz, CDCl ) d 172.8, 158.7, 147.5, 139.4, 134.3, 129.8, 128.3
(
2C, Ph-CH), 128.2, 128.0, 126.0, 124.3 (3C, 2Ph-CH, Naphthyl-C),
1
2
23.9, 121.2, 111.6, 104.1, 96.4, 52.2, 25.8; IR (KBr):
m
3069,
Fig. 1. Naturally occuring mollugin (1) and 3,4-dihydromollugin (2).
ꢁ1
953, 1734, 1651, 1590, 1444, 1337, 1238, 1166, 1097, 762 cm
;
+
HRMS (EI ): m/z: calcd for C21
16 4
H O : 332.1049. Found: 332.1050.
2
.2.2.4. Phenethyl 6-hydroxy-2,2-dimethyl-2H-benzo[h]chromene-5-
ture. The reaction mixture was stirred at room temperature for
0 h. The reaction mixture was quenched by addition of 1 N HCl
30 mL) solution and the aqueous solution was extracted with
ethyl acetate (40 mL ꢀ 3). The combined organic extracts were
washed with water, dried (MgSO ), and evaporated under vacuum.
Flash chromatography on silica gel using hexane/ethyl acetate
3:1) afforded methyl 1,4-dihydroxy-2-naphthoate or phenethyl
1
carboxylate (9). Yellow solid, 3.18 g, 85% yield. Mp 89–90 °C;
NMR (300 MHz, CDCl ) d 12.06 (s, 1H), 8.25 (d, J = 8.1 Hz, 1H),
.05 (d, J = 8.4 Hz, 1H), 7.48 (dd, J = 8.4, 7.2 Hz, 1H), 7.37 (dd,
J = 8.1, 7.2 Hz, 1H), 7.24–7.09 (m, 5H), 6.78 (d, J = 9.9 Hz, 1H),
H
1
(
3
8
4
5
2
1
1
6
2
1
C
.44 (d, J = 9.9 Hz, 1H), 4.53 (t, J = 6.9 Hz, 2H), 3.00 (t, J = 6.9 Hz,
1
3
3
H), 1.37 (s, 6H); C NMR (75 MHz, CDCl ) d 171.9, 156.4, 141.4,
(
37.5, 129.2, 128.9 (2C, Phenyl-CH), 128.9, 128.5 (2C, Phenyl-CH),
28.4, 126.7, 126.2, 125.0, 123.9, 122.4, 121.8, 112.6, 102.2, 74.5,
1
,4-dihydroxy-2-naphthoate.
3
6.3, 34.9, 26.8 (2C, CH ); IR (KBr): m 3289, 3067, 3030, 2974,
2.2.1.1. Methyl 1,4-dihydroxy-2-naphthoate. See Ref. [20].
928, 1736, 1646, 1578, 1497, 1439, 1392, 1358, 1325, 1238,
ꢁ1
+
166, 1046, 1011, 808, 770, 744 cm ; HRMS (EI ): m/z: calcd for
: 374.1518; Found: 374.1518.
2
7
.2.1.2. Phenethyl 1,4-dihydroxy-2-naphthoate. Yellow solid, 2.31 g,
24 22 4
H O
1
3
5% yield. Mp 156–157 °C; H NMR (300 MHz, CDCl ) d 14.08 (s,
OH), 11.41 (s, OH), 8.27 (d, J = 8.1 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H),
2.2.2.5. Phenethyl 6-hydroxy-2-methyl-2-(4-methylpent-3-en-1-yl)-
7
7
.52 (dd, J = 8.1, 6.9 Hz, 1H), 7.43 (dd, J = 8.1, 6.9 Hz, 1H), 7.28–
.12 (m, 5H), 7.05 (s, 1H), 4.47 (t, J = 6.9 Hz, 2H), 3.00 (t,
2H-benzo[h]chromene-5-carboxylate (11). Yellow liquid, 3.89 g, 88%
1
yield. H NMR (300 MHz, CDCl
3
) d 12.29 (s, 1H), 8.45 (d, J = 8.1 Hz,
1
3
J = 6.9 Hz, 2H); C NMR (75 MHz, CDCl
3
) d 170.6, 154.4, 144.7,
37.5, 129.5, 128.8 (2C, Phenyl-CH), 128.5 (2C, Phenyl-CH), 128.4,
26.5, 125.8, 125.3, 123.5, 122.1, 104.6, 104.4, 65.5, 34.9; IR
3382, 3055, 2987, 2925, 1732, 1650, 1599, 1453, 1405,
1H), 8.27 (d, J = 8.1 Hz, 1H), 7.65 (dd, J = 8.1, 7.5 Hz, 1H), 7.54 (dd,
J = 8.1, 7.5 Hz, 1H), 7.45–7.29 (m, 5H), 7.01 (d, J = 9.9 Hz, 1H),
5.61 (d, J = 9.9 Hz, 1H), 5.21 (t, J = 6.9 Hz, 1H), 4.68 (t, J = 6.9 Hz,
1
1
(
KBr):
m
2H), 3.15 (t, J = 6.9 Hz, 2H), 2.32–2.41 (m, 2H), 1.92–1.86 (m, 2H),
ꢁ1
+
13
1
345, 1265, 1153, 1095, 1071, 895, 743 cm ; HRMS (EI ): m/z:
1.75 (s, 3H, CH
3 3 3
), 1.65 (s, 3H, CH ), 1.54 (s, 3H, CH ); C NMR
calcd for C19
H
16
O
4
: 308.1049; Found: 308.1052.
(75 MHz, CDCl
(
3
) d 171.8, 156.3, 141.3, 137.5, 131.4, 129.1, 128.8
2C, Phenyl-CH), 128.7, 128.4 (2C, Phenyl-CH), 127.6, 126.6,
1
3
3
1
7
4
26.0, 124.9, 124.1, 123.9, 122.7, 121.7, 112.4, 102.1, 76.6, 66.2,
2
.2.2. General procedure for the synthesis of mollugin (1) and its
9.7, 34.8, 25.6 (CH ), 24.6 (CH ), 22.4, 17.5 (CH ); IR (neat): m
3
3
3
analogues 5, 7, 9, 11
A solution of alky 1,4-dioxo-1,4-dihydronaphthalene-2-carbox-
ylates (10.0 mmol), aldehyde (10.0 mmol), phenylboronic acid
287, 3064, 3029, 2969, 2923, 1723, 1647, 1579, 1496, 1443,
388, 1361, 1323, 1234, 1180, 1101, 1011, 905, 809, 770, 743,
ꢁ
1
+
30 4
00 cm ; HRMS (EI ): m/z: calcd for C29H O : 442.2144; Found:
(
(
10 mmol) and glacial AcOH (10 mL) in anhydrous toluene
200 mL) was refluxed for 8 h under N in an apparatus fitted with
42.2147.
2
a Dean–Stark trap. The mixture was cooled, concentrated under
vacuum, and the residue was extracted with several portions of
2
.2.3. General procedure for the synthesis of 3,4-dihydroxy mollugin
(2) and its analogues 6, 8, 10, and 12
CH
with H
SO ), the solvent was evaporated under vacuum, and the crude
2
Cl
2
(30 mL). The combined extract was washed successively
To a solution of mollugin (1) or its analogues 5, 7, 9, and 11
1 mmol) in anhydrous ethyl acetate (20 mL) in a Parr bottle was
2
O (30 mL), NaHCO (50 mL), and brine (30 mL), dried (Na2-
3
(
4
added 10% Pd/C (30 mg). The bottle was shaken for 5 h at 20 psi
of H . Removal of the solvent at reduced pressure left an oily resi-
due, which was then purified by column chromatography on silica
gel using hexane/ethyl acetate (15:1) to give the corresponding
hydrogenated products.
product was purified by flash chromatography on silica gel hex-
ane/ethyl acetate (5:1) to give the corresponding products.
2
2.2.2.1. Mollugin (1). See Refs. [20–25].
2.2.2.2. Methyl 6-hydroxy-2-methyl-2-(4-methylpent-3-en-1-yl)-2H-
2.2.3.1. 3,4-Dihydroxy mollugin (2). See Ref. [20].
benzo[h]chromene-5-carboxylate (5). Yellow liquid, 3.24 g, 92%
1
yield.
J = 8.4 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.61 (dd, J = 8.4, 7.2 Hz,
H), 7.50 (dd, J = 8.4, 7.2 Hz, 1H), 7.14 (d, J = 9.9 Hz, 1H), 5.65 (d,
J = 9.9 Hz, 1H), 5.13 (t, J = 7.2 Hz, 1H), 4.00 (s, 3H), 2.24–2.16 (m,
H
NMR (300 MHz, CDCl
3
)
d
12.21 (1H, s), 8.38 (d,
2.2.3.2. Methyl 6-hydroxy-2-methyl-2-(4-methylpentyl)-3,4-dihydro-
2H-benzo[h]chromene-5-carboxylate (6). Yellow liquid, 349 mg,
1
1
98% yield. H NMR (300 MHz, CDCl
3
) d 12.23 (s, 1H), 8.37 (d,
J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.60 (1H, dd, J = 8.4,
7.5 Hz), 7.49 (1H, dd, J = 8.4, 7.5 Hz), 3.97 (s, 3H), 3.05 (t,
J = 6.9 Hz, 2H,), 1.85–1.80 (m, 2H), 1.76–1.65 (m, 2H), 1.61–1.58
2
H), 1.85–1.78 (m, 2H), 1.66 (s, 3H, CH
s, 3H, CH
3
3
), 1.56 (s, 3H, CH ), 1.47
1
3
(
3
3
); C NMR (75 MHz, CDCl ) d 172.4, 156.3, 141.4,
1
1
1
1
31.6, 129.2, 128.8, 128.1, 126.2, 125.0, 124.1, 124.0, 122.5,
21.8, 112.4, 102.1, 76.7, 52.2, 39.8, 25.6 (CH ), 24.7 (CH ), 22.5,
7.5 (CH ); IR (neat) 2968, 2922, 1733, 1651, 1579, 1442, 1363,
332, 1236, 1101, 1013, 808, 771 cm ; HRMS (EI ): m/z: calcd
: 352.1675. Found: 352.1677.
(m, 2H), 1.56–1.45 (m, 2H), 1.35 (s, 3H, CH
3
), 1.26–1.17 (m, 1H),
); C NMR (75 MHz, CDCl ) d 173.0,
156.1, 141.3, 129.5, 129.0, 125.6, 124.3, 123.7, 121.5, 111.7,
105.1, 74.9, 52.0, 39.7, 39.4, 31.6, 27.8 (CH ), 23.4, 23.0, 22.6
(CH ), 22.5 (CH ), 21.3; IR (neat) 3071, 2949, 2869, 1734, 1651,
1
3
3
3
0.89 (d, J = 6.6 Hz, 6H, 2CH
3
3
3
m
ꢁ1
+
3
for C22
H
24
O
4
3
3
m