Synthesis of Pseudodeflectusin and Ustusorane C
solid. IR (KBr) cm : 3019, 1720, 1611, 1442, 1216, 1124, 756, 669.
1639
ꢂ1
(ꢀ)-Ustusorane C, (ꢀ)-2. To a solution of (ꢀ)-1 (35.1 mg,
1
.
H-NMR (600 MHz, CDCl3) ꢂ: xxxx1.56 (d, 3H, J ¼ 6:3 Hz), 3.03 (s,
0.13 mmol) in MeOH (5 ml) was added TsOH H2O (9.3 mg, 49 mmol).
1
1
1
1
H), 3.04 (d, 1H, J ¼ 5:5 Hz), 4.69–4.74 (m, 1H), 4.81 (d, 1H, J ¼
The reaction mixture was stirred for 1 h. The reaction was quenched by
adding H2O. The aqueous layer was extracted with EtOAc. The
combined extract was washed with brine, dried over Na2SO4, and
concentrated in vacuo. The residue was purified by silica gel
chromatography (hexane:EtOAc ¼ 5:1) to afford (ꢀ)-2 (36.5 mg,
8:4 Hz), 4.87 (d, 1H, J ¼ 18:4 Hz), 7.07 (d, 1H, J ¼ 7:7 Hz), 7.85 (d,
1
3
H, J ¼ 7:7 Hz). C-NMR (100 MHz, CDCl3) ꢂ: 20.7, 35.8, 74.5, 75.9,
11.8, 121.4, 122.3, 129.3, 150.1, 161.4, 173.8, 197.8. HRMS (ESI):
þ
calcd. for C12H10O4Na (½M þ Naꢃ ), 241.0471; found, 241.0466. (7R)-
ꢁ
24
ꢂ1
(
ꢂ)-8: mp ¼ 236 C; ½ꢁꢃD ¼ ꢂ126:5 (c 0.64, CHCl3).
quant.) as a colorless needle. R (KBr) cm : 2920, 1696, 1656, 1604,
1
434, 1370, 1288, 1122, 1096, 1055, 956, 860, 765. 1H-NMR
7
-Methyl-2-(1-methylethylidine)-7H-furo[3,2-h]isochromene-3,9(2H,
(600 MHz, CDCl ) ꢂ: 1.40 (d, 3H, J ¼ 6:3 Hz), 2.12 (s, 3H), 2.36
3
6
H)-dione ((ꢀ)-9). To a solution of (ꢀ)-8 (458 mg, 2.10 mmol) in
(s, 3H), 2.71 (dd, 1H, J ¼ 11:0 Hz, 17.2 Hz), 2.77 (dd, 1H, J ¼ 3:4 Hz,
.
acetone (25 ml) and 1,2-dichloroethane (25 ml) was added TsOH H2O
601.3 mg, 3.16 mmol). The reaction mixture was refluxed and stirred
17.2 Hz), 3.63 (s, 3H), 4.29–4.33 (m, 1H), 5.71 (s, 1H), 6.87 (d, 1H,
1
3
(
J ¼ 7:9 Hz), 7.60 (d, 1H, J ¼ 7:9 Hz). C-NMR (100 MHz, CDCl ) ꢂ:
3
for 5 h. The reaction was quenched by adding a saturated aqueous
sodium hydrogen carbonate solution. The aqueous layer was extracted
with CHCl3. The combined extract was washed with brine, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by silica
gel chromatography (hexane:EtOAc ¼ 1:1 to 1:2) to afford (ꢀ)-9
17.4, 20.2, 21.1, 35.9, 55.7, 62.8, 94.7, 119.1, 122.0, 122.6, 123.7,
132.0, 143.8, 145.3, 162.1, 183.3. HRMS (ESI): calcd. for
þ
C16H18O Na (½M þ Naꢃ ), 297.1097; found, 297.1087. (7R)-(þ)-2:
4
ꢁ
23
23
mp ¼ 147 C; ½ꢁꢃ
D
¼ þ54:3 (c 0.12, MeOH); ½ꢁꢃ
D
¼ þ6:0
(c 0.10, CHCl ).
3
(
377 mg, 70%) as a needle, (ꢀ)-10 (52 mg, 9%) as a 1:1 diastereomeric
ꢂ1
mixture, and recovered (ꢀ)-8 (18 mg, 4%). (ꢀ)-9. IR (KBr) cm
:
019, 1727, 1699, 1651, 1607, 1435, 1286, 1216, 1178, 1117, 755, 688.
8
-Hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromene-7-carbal-
3
1
dehyde ((ꢀ)-12). To a solution (ꢀ)-11 (3.90 g, 21.9 mmol) in dry
H-NMR (600 MHz, CDCl3) ꢂ: 1.56 (d, 3H, J ¼ 6:3 Hz), 2.33 (s, 3H),
.40 (s, 3H), 3.02 (s, 1H), 3.03 (d, 1H, J ¼ 8:8 Hz), 4.68–4.73 (m, 1H),
CH2Cl2 (15.0 ml) was added Cl2CHOMe (10.0 g, 87.0 mmol) at
2
ꢁ
ꢂ10 C. To the resulting mixture was added dropwise TiCl4 (9.5 ml,
13
7
.01 (d, 1H, J ¼ 7:7 Hz), 7.89 (d, 1H, J ¼ 7:7 Hz). C-NMR
ꢁ
8
6.6 mmol) at ꢂ10 C. The reaction mixture was stirred overnight at
(
100 MHz, CDCl3) ꢂ: 17.5, 20.7, 35.8, 74.5, 110.8, 121.3, 124.3,
ꢁ
ꢂ10 C. The reaction was quenched by adding a cold 1 M aqueous HCl
solution. The aqueous layer was extracted with CH2Cl2. The combined
extract was washed with brine, dried over Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel chromatography
1
29.2, 135.1, 145.1, 148.2, 161.2, 164.1, 182.1, 182.1. HRMS (ESI):
þ
23
calcd. for C15H14O4Na (½M þ Naꢃ ), 281.0784; found, 281.0782.
ꢁ
(
7R)-(ꢂ)-9: mp ¼ 217{218 C; ½ꢁꢃD ¼ ꢂ102:8 (c 0.76, CHCl3).
(
and the ortho-formyl isomer (0.36 g, 8%) as a white solid. IR
hexane:EtOAc ¼ 1:1) to afford (ꢀ)-12 (3.94 g, 87%) as a white solid
2
-(1-Hydroxy-1-methylethyl)-7-methyl-7H-furo[3,2-h]isochromene-
3
3
1
,9(2H,6H)-dione ((ꢀ)-10). 1H-NMR (600 MHz, CDCl3) ꢂ: 1.33 (s,
H), 1.37 (s, 3H), 1.38 (s, 3H), 1.40 (s, 3H), 1.56 (d, 3H, J ¼ 6:3 Hz),
.56 (d, 3H, J ¼ 6:3 Hz), 3.01–3.04 (m, 2H), 3.01–3.04 (m, 2H), 4.56
ꢂ1
1
(
KBr) cm : 3020, 1685, 1617, 1433, 1272, 1216, 1129, 757, 669. H-
NMR (600 MHz, CDCl3) ꢂ: 1.57 (d, 3H, J ¼ 6:4 Hz), 3.00 (d, 1H,
J ¼ 2:6 Hz), 3.01 (s, 1H), 4.79 (m, 1H), 6.82 (d, 1H, J ¼ 7:9 Hz), 8.00
(
s, 1H), 4.61 (s, 1H), 4.67–4.76 (m, 1H), 4.67–4.76 (m, 1H), 6.99 (d,
13
(
d, 1H, J ¼ 7:9 Hz), 10.49 (s, 1H), 11.80 (s, 1H). C-NMR (100 MHz,
1
7
H, J ¼ 7:7 Hz), 6.99 (d, 1H, J ¼ 7:7 Hz), 7.81 (d, 1H, J ¼ 7:7 Hz),
CDCl3) ꢂ: 20.5, 34.7, 75.9, 109.4, 118.2, 123.0, 134.6, 146.5, 164.1,
13
.81 (d, 1H, J ¼ 7:7 Hz) (diastereomeric mixture).
C
NMR
þ
1
2
69.2, 187.9. HRMS (ESI): calcd. for C11H10O4Na (½M þ Naꢃ ),
(
100 MHz, CDCl3) ꢂ: 20.1, 20.7, 24.6, 24.7, 24.8, 24.9, 35.8, 35.9,
1
29.0471; found, 229.0487. o-Formyl isomer. H-NMR (400 MHz,
7
1
1
2.3, 72.5, 74.4, 74.4, 90.9, 91.2, 111.4, 111.4, 121.2, 121.3, 122.9,
23.0, 129.3, 129.3, 150.3, 150.3, 161.1, 161.1, 172.7, 172.8, 198.6,
CDCl3) ꢂ: 1.59 (d, 3H, J ¼ 8:0 Hz), 3.07 (dd, 1H, J ¼ 11:6 Hz,
1
7.6 Hz), 3.96 (dd, 1H, J ¼ 3:0 Hz, 17.6 Hz), 4.72 (m, 1H), 7.06 (d,
H, J ¼ 8:4 Hz), 7.94 (d, 1H, J ¼ 8:4 Hz), 10.02 (s, 1H), 11.95 (s, 1H).
98.8 (diastereomeric mixture). HRMS (ESI): calcd. for C15H16O5Na
1
þ
(
½M þ Naꢃ ), 299.0889; found, 299.0893.
ꢁ
22
(
3R)-(ꢂ)-12: mp ¼ 117{118 C; ½ꢁꢃD ¼ ꢂ114:3 (c 0.78, CHCl3).
Dehydration of (ꢀ)-10. To a solution of (ꢀ)-10 (32.2 mg, 0.12
8
-Hydroxy-3-methyl-7-propionyl-3,4-dihydro-1H-isochromen-1-one
mmol) in pyridine (2.3 ml) were added methanesulfonyl chloride
(
(ꢀ)-13). To a solution of (ꢀ)-12 (20.6 mg, 0.10 mmol) in THF
(
40 ml, 0.52 mmol) and then 4-dimethylaminopyridine (1.4 mg,
1 mmol). The reaction mixture was stirred for 18 h. The reaction
(
2.0 ml) was added EtMgBr (220 ml, a 1.0 M solution in Et2O,
1
ꢁ
0
.22 mmol) at ꢂ5 C. The mixture was stirred at rt for 40 min. The
was quenched by adding a 10% HCl aqueous solution. The aqueous
layer was extracted with CHCl3. The combined extract was washed
with brine, dried over Na2SO4, and concentrated in vacuo. The residue
was purified by silica gel chromatography (hexane:EtOAc ¼ 1:1) to
afford (ꢀ)-9 (23.5 mg, 78%).
reaction was then quenched by adding a 1 M HCl aqueous solution. The
mixture was diluted with EtOAc. After the layers had been separated,
the organic layer was successivelywashed with H2O and brine, dried
(
Na2SO4), and concentrated.
To a solution of the residue in CH2Cl2 (2.5 ml) was added MnO2
159 mg, 85% purity, 1.56 mmol), and the mixture was stirred for 3 h.
(
(
.34 mmol) in dry THF (10 ml) was added dropwise DIBAL (0.42 ml of
ꢀ)-Pseudodeflectusin, (ꢀ)-1. To a solution of (ꢀ)-9 (88.5 mg,
MnO2 (239 mg, 85% purity, 2.34 mmol) was then added to the mixture,
and the mixture was stirred for 13 h. The mixture was filtered through
Celite and then washed with CH Cl . The solvent was removed under
0
ꢁ
a 0.97 M solution in n-hexane, 0.41 mmol) at ꢂ78 C. The reaction
ꢁ
mixture was stirred at ꢂ78 C for 1 h. The reaction was quenched by
2
2
reduced pressure. The residue was purified by silica gel chromatog-
raphy (hexane:EtOAc ¼ 2:1) to give (ꢀ)-13 (12.2 mg, 52%) as a white
adding a saturated aqueous Na2SO4 solution. The resulting mixture was
vigorously stirred, filtered through Celite, washed with EtOAc and
concentrated in vacuo. The residue was purified by silica gel
chromatography (hexane:EtOAc ¼ 2:1 to 1:1) to afford (ꢀ)-1 (16.7
ꢁ
ꢂ1
solid; mp ¼ 103{104 C. IR (KBr) cm : 2978, 2930, 1667, 1614,
1
424, 1389, 1274, 1224, 1125, 960, 816, 632. 1H-NMR (600 MHz,
CDCl3) ꢂ: 1.20 (t, 3H, J ¼ 7:2 Hz), 1.55 (d, 3H, J ¼ 6:3 Hz), 2.97–2.98
(m, 2H), 3.09–3.13 (m, 2H), 4.71–4.77 (m, 1H), 6.77 (d, 1H,
J ¼ 7:9 Hz), 8.00 (d, 1H, J ¼ 7:9 Hz), 12.3 (s, 1H). 13C-NMR
mg, 19%) as a crystal and recovered (ꢀ)-9 (62.4 mg, 71%). IR
ꢂ1
1
(
KBr) cm : 3399, 3019, 1697, 1652, 1614, 1438, 1119, 1079, 1027,
8
54, 669. H-NMR (600 MHz, CDCl3) ꢂ: 1.40 (d, 3H, J ¼ 6:2 Hz), 2.13
(
100 MHz, CDCl3) ꢂ: 8.2, 20.7, 34.9, 36.6, 75.7, 109.6, 117.9, 125.2,
(
s, 3H), 2.37 (s, 3H), 2.72 (dd, 1H, J ¼ 11:0 Hz, 17.2 Hz), 2.79 (dd, 1H,
1
37.2, 144.7, 162.3, 169.2, 201.5. HRMS: calcd. for C13H14O4Na
J ¼ 3:1 Hz, 17.2 Hz), 2.98 (d, 1H, J ¼ 4:2 Hz), 4.44–4.78 (m, 1H), 6.28
þ
(
½M þ Naꢃ ), 257.0784; found, 257.0785.
(
1
d, 1H, J ¼ 4:2 Hz), 6.89 (d, 1H, J ¼ 7:9 Hz), 7.62 (d, 1H, J ¼ 7:9 Hz).
3
C-NMR (100 MHz, CDCl3) ꢂ: 17.4, 20.2, 21.0, 35.9, 62.8, 87.6,
19.5, 121.9, 122.6, 123.6, 132.3, 143.7, 145.2, 161.9, 183.2. HRMS
1
2,6,7-Trimethyl-7,8-dihydro-4H,10H-pyrano[4,3-h]chromene-4,10-
dione ((ꢀ)-14). A solution of (ꢀ)-13 (18.6 mg, 0.079 mmol), Ac2O
þ
(
ESI): calcd. for C15H16O4Na (½M þ Naꢃ ), 283.0940; found,
ꢁ
23
2
83.0945. (7R)-(þ)-1: mp ¼ 170 C; ½ꢁꢃD ¼ þ63:7 (c 0.08, MeOH).
(15 ml, 0.16 mmol) and DBU (50 ml, 0.33 mmol) in pyridine (1.5 ml)
was stirred at 60 C for 6 h. The mixture was then concentrated in
ꢁ
The enantiomeric excess was determined to be 99% ee by HPLC, using
a chiral column (Daicel Chiralpak OD; hexane:2-propanol ¼ 15:1;
flow rate 0.5 ml/min. (7R)-(þ)-1, RT ¼ 53 min. (7S)-(ꢂ)-1, RT ¼ 37
min; monitoring at 254 nm).
vacuo. The residue was purified by PTLC (hexane:EtOAc ¼ 1.5:1) to
ꢁ
give (ꢀ)-14 (10.9 mg, 53%) as a white solid, mp ¼ 191{193 C. IR
ꢂ1
(KBr) cm : 2971, 2925, 2858, 1725, 1637, 1437, 1400, 1273, 1172,