Synthesis of C-7 oxidized abietane diterpenes from racemic ferruginyl methyl ether

Article abstract of DOI:10.1016/S0040-4020(03)00883-4

A series of naturally occurring C-7 oxidized abietane diterpenes have been synthesized from racemic ferruginyl methyl ether in high yields. 6-Hydroxyl-5,6-dehydrosugiol (7) can be converted into stable xanthoperol (12) using high temperature. Among the products, the structures of sugiyl methyl ether (2) and 6(-hydroxysugiyl methyl ether (8) were determined by X-ray analysis.

Full text of DOI:10.1016/S0040-4020(03)00883-4

Tetrahedron 59 (2003) 5737–5741
Synthesis of C-7 oxidized abietane diterpenes from racemic
ferruginyl methyl ether
*
Anpai Li, Xuegong She, Jiyong Zhang, Tongxing Wu and Xinfu Pan
Department of Chemistry, National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000,
People’s Republic of China
Received 13 January 2003; revised 9 May 2003; accepted 29 May 2003
Abstract—A series of naturally occurring C-7 oxidized abietane diterpenes have been synthesized from racemic ferruginyl methyl ether in
high yields. 6-Hydroxyl-5,6-dehydrosugiol (7) can be converted into stable xanthoperol (12) using high temperature. Among the products,
the structures of sugiyl methyl ether (2) and 6(-hydroxysugiyl methyl ether (8) were determined by X-ray analysis. q 2003 Published by
Elsevier Science Ltd.
1. Introduction
best of our knowledge on these naturally occurring
molecules and their structure–activity relationships, com-
pounds 7 and 9 were synthesized for the first time.
Abietane diterpenes are widely distributed, naturally
occurring products in the plant kingdom. Many of them
exhibit significant biological activities, e.g. antibiotic,1 anti-
tumor,2 anti-virus,3 antimalarial,4 anti-oxidant effects.5 Due
to their wide distribution and interesting bioactivities, many
synthetic studies have been reported.6 As part of our
continuing efforts to synthesize this kind of biologically
active compounds,7 a series of C-7 oxidized abietane
diterpenes were synthesized from racemic ferruginyl methyl
ether (1), including sugiol (3),8 6-hydroxy-5,6-dehydro-
sugiol (7),9 6a-hydroxysugiol (9),10 5,6-dehydrosugiol
(11)11 and xanthoperol (12).12 Xanthoperol (12) is different
from the others in that it has cis-fused A/B rings (Fig. 1).13
Among these compounds, 5,6-dehydrosugiol (11) was first
isolated from Taxodium distichum Rich and showed
biological activity against KB tumors.14 6a-Hydroxysugiol
(9) was first isolated from the bark of Libocedrus formosana
Florin,15 and recently, Tanaka et al. reported that it showed
a strong inhibitory effect on EBV-EA induction.16 To the
2. Result and discussion
As shown in Scheme 1, oxidation of ferruginyl methyl ether
(1) with chromium oxide in acetic acid gave sugiyl methyl
ether (2). From the X-ray crystallographic analysis, the
trans conjunction of its A/B rings can be confirmed (Fig. 2).
Demethylation of 2 with sodium ethanethiolate in N,N-
dimethylformamide under reflux afforded suginol (3).
Compound 2 was treated with isopropenyl acetate in the
presence of p-toluenesulfonic acid monohydrate under
reflux to afford acetate 4.
Oxidation of compound 4 with m-chloroperoxybenzoic acid
in dichloromethane afforded 6a-acetoxy-12-methoxy-
abieta-8, 11, 13-triene-7-one (5) in 93% yield. Treatment
of 5 with K2CO3 in methanol and water (3:1) afforded the
Figure 1.
Keywords: abietane; terpenes and terpenoids; biologically active compounds; X-ray crystal structures.
*
Corresponding author. Tel.: þ86-931-8912407; fax: þ86-931-8912582; e-mail: panxf@lzu.edu.cn
0040–4020/03/$ - see front matter q 2003 Published by Elsevier Science Ltd.
doi:10.1016/S0040-4020(03)00883-4

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A. Li et al. / Tetrahedron 59 (2003) 5737–5741
Scheme 1. Reagents and conditions: (a) CrO3/HOAc, 84%; (b) isopropenyl acetate, TsOH, reflux, 3 h, 99%; (c) m-CPBA, CH2Cl2; KI/H2O, Na2S2O3, 93%,
08C; (d) K2CO3, MeOH/H2O, 24 h, air, rt, 74%; (e) NaSEt, DMF, reflux, 98%; (f) O2, t-BuOK/t-BuOH, 1 h, 08C; 68%.
desired 6a-hydroxysugiyl methyl ether (8) in 74% yield
along with an oxidized product 6 in 22% yield. The yield of
the over-oxidized product 6 can be decreased to less than
5% by performing the reaction under argon. Compound 6
can also be obtained from sugiyl methyl ether (2) through
oxidation by oxygen in t-BuOK/t-BuOH. To further
ascertain the configuration of the C-6 hydroxyl group in
compound 8, an X-ray analysis was carried out (Fig. 2),
which confirmed the position of the a-hydroxyl group.
compounds 7, 9, 11 and 12 and their derivatives were also
prepared (Scheme 2). It was shown that demethylation of 8
with sodium ethanethiolate in N,N-dimethylformamide
under argon or air, respectively, produced different
products. Under argon the product was the demethylated
compound 9, while in air, the product was the demethylated
and oxidized compound 12. According to the literature,17
when the A/B rings are cis-fused, the d value of C4-a-
methyl group will be about 0.4 ppm; when the A/B rings are
trans-fused, the d value of C4-a-methyl group will be about
0.9–1.0 ppm. From the 1H NMR spectrum of 12, we found
To further investigate this family of natural products,
Figure 2.
Scheme 2. Reagents and conditions: (g) NaSEt, DMF, 1108C, 90%, Ar; (h) TsOH, PhH, reflux, Ar, 85%; (i) NaSEt, DMF, reflux, 98%; (j) NaSEt, DMF, reflux,
air, 5 h, 92%; (k) BBr3, CH2Cl2, 08C, 58%; (l) NaSEt, DMF, reflux, 91%; (m) .1158C.

A. Li et al. / Tetrahedron 59 (2003) 5737–5741
5739
the corresponding methyl signal at 0.3 ppm, thus a cis
conjunction in the A/B rings was deduced. Dehydration of 8
in benzene in the presence of p-toluenesulfonic acid
monohydrate under reflux afforded 5,6-dehydrosugiyl
methyl ether (10), which was subjected to demethylation
to afford the desired 5,6-dehydrosugiyl methyl ether (11).
Treatment of 6 with BBr3 in dichloromethane at 08C
afforded 6-hydroxy-5,6-dehydrosugiol (7), while treatment
of 6 with sodium ethanethiolate in N,N-dimethylformamide
under reflux afforded the demethylated isomer 12. Our
studies showed that compound 7 can be converted into 12
above 1158C.
3.1.2. Sugiol (3). To a solution of 2 (157 mg, 0.5 mmol) in
N,N-dimethylformamide (2 mL) was added ethanethiol
(0.4 mL, 5.5 mmol) and sodium hydride (132 mg,
5.5 mmol). The mixture was refluxed for 4 h and cooled
to room temperature. The mixture was poured into ice cold
5% hydrochloric acid and extracted with ethyl acetate; the
combined organic phases were washed with brine and dried
over anhydrous sodium sulfate. The organic solution was
evaporated in vacuo and the residue was purified by column
chromatography to afford 3 (143 mg, 98%) as colorless
crystals, mp 247–2488C. 1H NMR (400 MHz, DMSO-d6) d
0.86 (s, 3H), 0.92 (s, 3H), 1.11 (d, J¼6.8 Hz, 3H), 1.13 (s,
3H), 1.15 (d, J¼6.8 Hz, 3H), 1.20–2.15 (m, 7H), 2.41–2.56
(m, 2H), 3.13 (sept., 1H, J¼6.8 Hz), 6.78 (s, 1H), 7.64 (s,
1H), 10.23 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d
18.43, 21.08, 22.15, 22.32, 22.98, 26.02, 32.24, 32.81,
35.46, 37.41, 39.92, 40.80, 49.04, 109.26, 122.53, 124.94,
132.44, 155.75, 160.05, 196.40. IR (film)/cm21: 3118,
2929, 1643, 1600, 1583, 1568, 1310, 1268. HRMS (ESI):
3. Experimental
3.1. General
The 1H NMR spectra were recorded on a Bruker AM-
400 MHz spectrometer. 13C NMR spectra were recorded on
a Bruker AM-100 MHz spectrometer. The chemical shifts
are reported in ppm relative to TMS. IR spectra were
recorded on a Nicolet 170 SXFT-IR spectrometer. HRMS
spectra were recorded on a Bruker, APEXII spectrometer.
Mass spectra were recorded on a ZAB-HS mass spec-
trometer (EI). Column chromatography was generally
performed on silica gel (200–300 mesh) eluting with
petroleum ether/ethyl acetate (30:1!8:1, v/v) and TLC
inspections were done on silica gel GF254 plates with
petroleum ether/ethyl acetate (20:1!5:1, v/v) if not noted
otherwise.
found
MþH¼301.2171,
C20H28O2
required
MþH¼301.2162. m/z (EI): 300 (71 Mþ), 285 (100), 243
(33), 217 (61), 203 (59%).
3.1.3. 7-Acetoxy-12-methoxyabieta-6,8,11,13-tetraene
(4). To a solution of 2 (1.22 g, 3.83 mmol) in isopropenyl
acetate was added a catalytic mount of p-toluenesulfonic
acid monohydrate. The mixture was refluxed for 3 h, cooled
to room temperature and quenched with saturated sodium
hydrogen carbonate. After extraction with diethyl ether, the
combined organic layers were washed with saturated
sodium hydrogen carbonate and brine, then dried over
anhydrous sodium sulfate. After the ether solution was
evaporated in vacuo, the residue was purified by column
chromatography to afford 4 (1.36 g, 99%) as a yellow oil. 1H
NMR (400 MHz, CDCl3) d 0.95 (s, 3H), 1.12 (s, 3H), 1.23
(d, J¼7.0 Hz, 3H), 1.26 (s, 3H), 1.28 (d, J¼7.0 Hz, 3H),
1.27–2.33 (m, 7H), 2.34 (s, 3H), 3.32 (sept., J¼7.0 Hz, 1H),
3.88 (s, 3H), 5.59 (d, J¼2.7 Hz, 1H), 6.76 (s, 1H), 7.04 (s,
1H). 13C NMR (100 MHz, CDCl3) d 18.85, 20.18, 20.69,
22.26, 22.36, 22.72, 26.54, 32.53, 32.95, 35.90, 38.48,
40.83, 50.60, 55.30, 104.79, 113.52, 119.18, 121.95, 133.63,
145.51, 147.86, 157.19, 169.12. IR (film)/cm21: 1738,
1637, 1600, 1507, 1468, 1254. HRMS (ESI): found
MþH¼357.2427, C23H32O3 required MþH¼357.2431.
m/z (EI): 356 (15 Mþ), 314 (22), 299 (29), 243 (18), 232
(85%).
3.1.1. Sugiyl methyl ether (2). To a solution of 1 (1.5 g,
5 mmol) in acetic acid (20 mL) was added chromium oxide
(600 mg, 6 mmol) in acetic acid (5 mL) at room tempera-
ture. The mixture was stirred for 0.5 h, then water was added
to quench the reaction. After extraction with dichloro-
methane, the combined organic layers were washed with
saturated sodium hydrogen carbonate and brine. The
organic solution was evaporated in vacuo, and the crude
product was purified by column chromatography to give
compound 2 (1.32 g, 84%) as white needle shape crystals,
mp 130–1328C. 1H NMR (400 MHz, CDCl3) d 0.93 (s, 3H),
1.00 (s, 3H), 1.23 (d, 3H, J¼7.0 Hz), 1.27 (d, 3H,
J¼7.0 Hz), 1.28 (s, 3H), 1.29–2.32 (m, 7H), 2.56–2.71
(m, 2H), 3.25 (sept., 1H, J¼7.0 Hz), 3.88 (s, 3H), 6.75 (s,
1H), 7.89 (s, 1H). 13C NMR (100 MHz, CDCl3) d 18.91,
21.35, 22.37, 22.52, 23.24, 26.51, 32.57, 33.29, 36.02,
37.98, 38.26, 41.37, 49.64, 55.37, 104.41, 124.11, 125.59,
135.20, 156.36, 161.63, 198.46. IR (film)/cm21: 1677,
1598, 1561, 1495, 1258. HRMS (ESI): found
MþH¼315.2323, C21H30O2 required MþH¼315.2319.
m/z (EI): 314 (72 Mþ), 299 (100), 257 (21), 231 (27), 177
(26%).
3.1.4. 6a-Acetoxy-12-methoxyabieta-8,11,13-trien-7-one
(5). A mixture of 4 (1.35 g, 3.8 mmol) and m-chloroperoxy-
benzoic acid (785 mg, 4.56 mmol) in dichloromethane
(20 mL) was stirred at room temperature for 12 h, then
ethyl ether was added. The mixture was washed succes-
sively with aqueous potassium iodide, aqueous sodium
thiosulfate, saturated sodium hydrogen carbonate and brine.
The organic phase was separated and dried over anhydrous
sodium sulfate. The ether solution was evaporated in vacuo
and the residue was purified by column chromatography to
afford 5 (1.32 g, 93%) as a white solid, mp 163–1648C, 1H
NMR (400 MHz, CDCl3) d 1.11 (s, 6H), 1.17 (d, J¼7.0 Hz,
3H), 1.22 (d, J¼7.0 Hz, 3H), 1.41 (s, 3H), 2.24 (s, 3H),
1.32–2.29 (m, 7H), 3.24 (sept., J¼7.0 Hz, 1H), 3.90 (s, 3H),
5.83 (d, J¼13 Hz, 1H), 6.76 (s, 1H), 7.90 (s, 1H). 13C NMR
(100 MHz, CDCl3) d 18.68, 21.36, 21.90, 22.23, 22.43,
X-Ray crystal data collection and refinement for 2: formula,
C21H30O2; Mr, 314.45; crystal system, monoclinic; space
˚
˚
˚
group, Pc; a, 11.991(2) A; b, 10.873(2) A; c, 14.778(3) A;
V, 1815.7(6) A ; Z, 4; Dc, 1.150 g cm23; F(000), 688; m,
3
˚
0.072 mm21; T, 293 K; independent reflections, 2179;
˚
observed data with I$3s(I), 1408; radiation (l/A),
Mo Ka; scan type, v/2u; 2umax, 508; R, 0.0295; Rw,
0.0555; goodness-of-fit indicator, 1.094.

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A. Li et al. / Tetrahedron 59 (2003) 5737–5741
25.06, 26.47, 33.68, 35.51, 38.48, 39.78, 42.86, 53.23,
55.40, 75.10, 104.22, 122.39, 126.30, 136.00, 155.28,
162.06, 170.43, 192.86. IR (film)/cm21: 1744, 1682, 1601,
1496, 1372, 1235. HRMS (ESI): found MþH¼373.2373,
C23H32O4 required MþH¼373.2373. m/z (EI): 372 (37
Mþ), 357 (10), 330 (35), 297 (22), 245 (37), 217 (100), 149
(50%).
1.24 (d, J¼7.0 Hz, 3H), 1.39 (s, 3H), 1.28–2.31 (m, 7H),
3.25 (sept., J¼7.0 Hz, 1H), 3.92 (s, 3H), 4.61 (dd, J¼13,
1.7 Hz, 1H), 6.77 (s, 1H), 7.92 (s, 1H). 13C NMR d 18.87,
21.84, 22.29, 22.44, 24.69, 26.53, 34.14, 35.79, 38.87,
39.59, 42.92, 55.40, 56.07, 73.82, 104.64, 121.18, 126.07,
135.94, 156.55, 162.35, 199.71. IR (film)/cm21: 1654,
1600, 1565, 1497, 1462, 1377, 1286. HRMS (ESI): found
MþH¼331.2275, C21H30O3 required MþH¼331.2268. m/z
(EI): 330 (36 Mþ), 315 (39), 301 (74), 245 (74), 217
(100%).
3.1.5. 6-Hydroxy-5,6-dehydrosugiyl methyl ether (6). To
a solution of t-BuOK (1.2 g) in t-BuOH (10 mL) was added
2 (106 mg), then oxygen was slowly bubbled in. After
stirring at 08C for 2 h, 5% dilute hydrochloric acid was
added until pH¼1. The solution was stirred for another 1 h,
then extracted with ether. The ether solution was evaporated
and the crude product was purified by column chromato-
graphy to afford 6 (76 mg, 68%) as white crystals, mp 144–
X-Ray crystal data collection and refinement for 8: formula,
C21H30O3; Mr, 330.45; crystal system, triclinic; space
˚
˚
˚
group, P1; a, 8.038 A; b, 10.391 A; c, 12.299 A; V,
909.8 A ; Z, 2; Dc, 1.206 g cm23; F(000), 360; m,
3
˚
0.079 mm21; T, 293 K; independent reflections, 1874;
1
˚
observed data with I$3s(I), 1365, radiation (l/A),
1458C. H NMR (400 MHz, CDCl3) d 1.22 (d, J¼6.8 Hz,
3H), 1.26 (d, J¼6.8 Hz, 3H), 1.45 (s, 6H), 1.55 (s, 3H),
1.47–2.41 (m, 6H), 3.28 (sept., J¼6.8 Hz, 1H), 3.92 (s, 3H),
6.87 (s, 1H), 7.19 (s, 1H), 8.00 (s, 1H). 13C NMR d 17.58,
22.33, 22.53, 26.62, 27.58, 28.11, 33.70, 35.04, 35.85,
37.78, 40.59, 55.43, 105.99, 120.44, 124.56, 136.28, 140.61,
143.76, 154.84, 161.14, 179.67. IR (film)/cm21: 1693,
1624, 1595, 1497, 1463, 1251. HRMS (ESI): found
MþH¼329.2117, C21H28O3 required MþH¼329.2111.
m/z (EI): 328 (100 Mþ), 285 (34), 259 (77), 243 (28), 217
(15%).
Mo Ka; scan type, v/2u; 2umax, 508; R, 0.0254; Rw,
0.0527; goodness-of-fit indicator, 1.059.
3.1.8. 6a-Hydroxysugiol (9). To a solution of 8 (99 mg,
0.3 mmol) in N,N-dimethylformamide (2 mL) under Ar was
added ethanethiol (0.3 mL, 4 mmol) and sodium hydride
(96 mg, 4 mmol). The mixture was heated to 1108C and
stirred for 5 h, then cooled to room temperature and poured
into ice cold 5% hydrochloric acid. The mixture was
extracted with ethyl acetate; the combined organic phases
were washed with brine and dried over anhydrous sodium
sulfate. The organic solution was evaporated in vacuo and
the residue was purified by column chromatography to
afford 9 (85 mg, 90%) as a white solid, mp 207–2088C. 1H
NMR (400 MHz, DMSO-d6) d 1.12 (s, 6H), 1.16 (d,
J¼6.8 Hz, 6H), 1.22 (s, 3H), 1.18–2.13 (m, 7H), 3.15 (sept.,
J¼6.8 Hz, 1H), 4.40 (dd, J¼12.3, 3.4 Hz, 1H), 4.79 (s, 1H),
6.79 (s, 1H), 7.67 (s, 1H), 10.32 (s, 1H). 13C NMR
(100 MHz, DMSO-d6) d 18.40, 21.65, 22.14, 22.28, 24.69,
26.07, 33.67, 35.91, 38.11, 38.43, 42.72, 54.84, 72.61,
109.21, 120.70, 125.43, 133.06, 155.57, 160.47, 198.47. IR
(film)/cm21: 3421, 1645, 1600, 1500, 1185, 1131. HRMS
(ESI): found MþH¼317.2114, C20H28O3 required
MþH¼317.2111. m/z (EI): 316 (16 Mþ), 301 (18), 287
(48), 231 (43), 203 (51%).
3.1.6. 6-Hydroxy-5,6-dehydrosugiol (7). To a solution of 6
(164 mg, 0.5 mmol) in dichloromethane (5 mL) was added
boron tribromide (0.2 mL) at 258C. The mixture was stirred
for 1 h at this temperature, then diluted with ether and
poured into ice water. The mixture was extracted with ethyl
ether. The combined organic layers were washed with brine
and dried over anhydrous sodium sulfate. After evaporation,
the residue was purified by flash column chromatography to
afford compound 7 (91 mg, 58%) as a white solid,
1
mp.1158C decomposition. H NMR (400 MHz, DMSO-
d6) d 1.17 (d, J¼6.8 Hz, 3H), 1.20 (d, J¼6.8 Hz, 3H), 1.35
(s, 6H), 1.42 (s, 3H), 1.23–2.28 (m, 6H), 3.18 (sept.,
J¼6.8 Hz, 1H), 6.95 (s, 1H), 7.76 (s, 1H), 8.04 (s, 1H),
10.28 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 16.99,
22.11, 22.31, 26.22, 27.38, 27.89, 33.08, 35.26, 35.32,
37.36, 39.57, 110.73, 119.41, 123.93, 133.70, 139.53,
143.87, 153.92, 159.44, 178.66. IR (film)/cm21: 3376,
2960, 1625, 1582, 1455, 1315, 1260. HRMS (ESI): found
MþH¼315.1962, C20H26O3 required MþH¼315.1955. m/z
(EI): 314 (7 Mþ), 285 (65), 243 (28), 217 (35), 203 (42), 149
(100%).
3.1.9. 5,6-Dehydrosugiyl methyl ether (10). To a solution
of 8 (99 mg, 0.3 mmol) in benzene (3 mL) was added a
catalytic amount of p-TsOH. The solution was refluxed for
6 h. After cooling, saturated sodium hydrogen carbonate
was added to the solution and the mixture was extracted
with ether. The combined organic layers were washed with
brine and dried over anhydrous sodium sulfate. After
evaporation, the crude product was purified by column
chromatography to give 10 (80 mg, 85%) as a white solid,
3.1.7. 6a-Hydroxysugiyl methyl ether (8). To a solution of
potassium carbonate (2 g, 145 mmol) in methanol and water
(3:1) was added 5 (1.12 g, 3 mmol). The mixture was stirred
for 24 h at room temperature, and then evaporated in vacuo.
Water and ethyl acetate were added to the residue. The
mixture was stirred to form two clear phases. After
separation, the aqueous phase was extracted with ethyl
acetate; the combined organic layers were washed with
brine and then dried over anhydrous sodium sulfate. The
crude product was purified by column chromatography to
afforded 6 (216 mg, 22%) and 8 (732 mg, 74%) as white
crystals. For compound 8: mp 171–1728C. 1H NMR
(400 MHz, CDCl3) d 1.20 (d, J¼7.0 Hz, 3H), 1.23 (s, 6H),
1
mp 156–1578C. H NMR (400 MHz, CDCl3) d 1.22 (d,
J¼6.8 Hz, 3H) 1.25 (d, J¼6.8 Hz, 3H), 1.27 (s, 3H), 1.36 (s,
3H), 1.54 (s, 3H), 1.43–2.46 (m, 6H), 3.25 (sept., J¼7.5 Hz,
1H), 3.90 (s, 3H), 6.46 (s, 1H), 6.86 (s, 1H), 7.99 (s, 1H). 13C
NMR (100 MHz, CDCl3) 16.65, 22.40, 22.50, 26.65, 29.16,
32.50, 32.63, 37.44, 37.80, 40.30, 41.33, 55.39, 105.55,
123.56, 124.08, 124.61, 135.99, 153.80, 160.78, 172.62,
185.12. IR (film)/cm21: 1646, 1598, 1497, 1464, 1253.
HRMS (ESI): found MþH¼313.2164, C21H28O2 required
MþH¼313.2162. m/z (EI): 312 (32 Mþ), 297 (77), 282
(43), 269 (26), 243 (25), 201 (17%).

A. Li et al. / Tetrahedron 59 (2003) 5737–5741
5741
3.1.10. 5,6-Dehydrosugiol (11). To a solution of 10 (78 mg,
References
0.25 mmol) in N,N-dimethylformamide (2 mL) was added
ethanethiol (0.2 mL, 2.6 mmol) and sodium hydride (62 mg,
2.6 mmol). The mixture was refluxed for 3 h and cooled to
room temperature. The mixture was poured into ice cold 5%
hydrochloric acid and extracted with ethyl acetate. The
combined organic phases were washed with brine and dried
over anhydrous sodium sulfate. The organic solution was
evaporated in vacuo and the residue was purified by column
chromatography to afford 11 (73 mg, 98%) as white
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1
crystals, mp 281–2828C. H NMR (400 MHz, DMSO-d6)
d 1.16 (d, J¼6.8 Hz, 3H), 1.18 (d, J¼6.8 Hz, 3H), 1.19 (s,
3H), 1.29 (s, 3H), 1.42 (s, 3H), 1.31–2.30 (m, 6H), 3.16
(sept., J¼6.8 Hz, 1H), 6.23 (s, 1H), 6.94 (s, 1H), 7.71 (s,
1H), 10.20 (s, 1H). 13C NMR d 18.00, 22.17, 22.35, 26.15,
28.85, 32.24, 32.51, 36.92, 37.29, 39.78, 40.44, 110.51,
121.62, 123.76, 123.59, 133.43, 153.44, 159.18, 172.21,
183.25. IR (film)/cm21: 3113, 2965, 1637, 1614, 1583,
1563, 1505, 1468, 1314. HRMS (ESI): found
MþH¼299.1998, C20H26O2 required MþH¼299.2006.
m/z (EI): 298 (21 Mþ), 283 (11), 229 (33), 213 (50%).
5. (a) Nakatani, N.; Iwatani, R. Agric. Biol. Chem. 1981, 45,
2385–2386. (b) Nakatani, N.; Iwatani, R. Agric. Biol. Chem.
1984, 48, 2081–2085.
6. (a) Engler, T. A.; Sampath, U. J. Org. Chem. 1989, 54,
5712–5727. (b) Edstrom, E. O.; Livinghouse, T. J. Org.
Chem. 1987, 52, 949–951. (c) Lee, H. J.; Ravn, M. M.; Coates,
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Nishiiri, S.; Yang, Z.; Imai, Y.; Tajima, S.; Okazaki, N.;
Kitano, Y.; Chiba, K. J. Chem. Soc., Perkin Trans. 1 2000,
2657–2664.
3.1.11. Xanthoperol (12). (a) To a solution of 6 (99 mg,
0.3 mmol) in N,N-dimethylformamide (2 mL) was added
ethanethiol (0.3 mL, 4 mmol) and sodium hydride (96 mg,
4 mmol). The mixture was refluxed for 4 h and then cooled
to room temperature. The mixture was poured into ice cold
5% hydrochloric acid and extracted with ethyl acetate. The
combined organic phases were washed with brine and dried
over anhydrous sodium sulfate. The organic solution was
evaporated in vacuo and the residue was purified by column
chromatography to afford 12 (86 mg, 91%) as yellow
crystals, mp 257–2588C. 1H NMR (400 MHz, DMSO-d6) d
0.31 (s, 3H), 0.82 (s, 3H), 1.11 (s, 3H), 1.16 (s, 6H), 1.32–
2.37 (m, 6H), 2.60 (s, 1H), 3.16 (sept., J¼6.4 Hz, 1H), 6.91
(s, 1H), 7.77 (s, 1H), 10.88 (s, 1H). 13C NMR d 18.40, 21.94,
22.09, 23.61, 26.32, 30.96, 34.71, 35.22, 37.94, 38.98,
40.98, 68.07, 110.59, 125.42, 127.95, 134.44, 150.18,
162.25, 179.04, 199.70. IR (film)/cm21: 3267, 2960, 1656,
1583, 1507, 1368, 1276. HRMS (ESI): found
MþH¼315.1961, C20H26O3 required MþH¼315.1955.
m/z (EI): 314 (16 Mþ), 300 (13), 271 (29), 217 (26), 204
(100%).
7. Gan, Y. H.; Li, A. P.; Pan, X. F.; Chan, A. S. C.; Yang, T. K.
Tetrahedron: Asymmetry 2000, 11, 781–787.
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35, 1279–1284. (b) Kuo, Y. H.; Yu, M. T. Phytochemistry
1996, 42, 779–781.
9. Yanagawa, T.; Hirose, Y. Mokuzai Gakkaishi 1971, 17,
306–310.
10. (a) See Ref. 8(a). (b) Ohtsu, H.; Iwamoto, M.; Ohishi, H.;
Matsunaga, S.; Tanaka, R. Tetrahedron Lett. 1999, 40,
6419–6422.
11. (a) Su, W. C.; Fang, J. M.; Cheng, Y. S. Phytochemistry 1996,
41, 225–227. (b) Kuo, Y. H.; Yu, M. T. Phytochemistry 1996,
42, 779–781.
12. (a) Bredenbery, J. B.; Gripenberg, J. Acta Chem. Scand. 1956,
10, 1511–1514. (b) Nasipuri, D.; Gula, M. J. Chem. Soc. 1962,
4248–4252.
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688–693.
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34, 3912–3918.
(b) To a solution of 8 (99 mg, 0.3 mmol) in N,N-
dimethylformamide (2 mL) under air was added ethanethiol
(0.3 mL, 4 mmol) and sodium hydride (96 mg, 4 mmol).
The mixture was refluxed for 5 h, then cooled to room
temperature. The reaction mixture was poured into ice-cold
5% hydrochloric acid and extracted with ethyl acetate. The
combined organic phases were washed with brine and dried
over anhydrous sodium sulfate. The organic solution was
evaporated in vacuo and purified by column chromato-
graphy to afford 12 (91 mg, 92%) as yellow crystals. The
physical and spectroscopic data of 12 were identical to these
of a sample prepared previously.
15. Kuo, Y. H.; Chang, B. H.; Lin, Y. T. J. Chin. Chem. Soc. 1975,
22, 49–52.
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Acknowledgements
We are grateful to the National Natural Science Foundation
of China (No. 29372050) for financial support.