The first total syntheses of (+)-hostmanin a and (+)-methyllinderatin

Article abstract of DOI:10.3987/COM-10-12084

The first total syntheses of (+)-hostmanin A (1) and (+)-methyllinderatin (3) were achieved in four steps from a known compound, 1-{2, 6-dihydroxy-4-methoxy-3-[(1R, 6R)-3-methyl-6-(1-methylethyl)-2-cyclohexen-1-yl] phenyl}ethanone (6). The absolute config

Full text of DOI:10.3987/COM-10-12084

HETEROCYCLES, Vol. 83, No. 1, 2011
143
HETEROCYCLES, Vol. 83, No. 1, 2011, pp. 143 - 151. © The Japan Institute of Heterocyclic Chemistry
Received, 18th October, 2010, Accepted, 22nd November, 2010, Published online, 24th November, 2010
DOI: 10.3987/COM-10-12084
THE FIRST TOTAL SYNTHESES OF (+)-HOSTMANIN A AND
(+)-METHYLLINDERATIN
Junko Kitao, Naoko Kitamura, Nozomi Kumo, Kenji Arimitsu, Hiroki
Iwasaki, Minoru Ozeki, Ai Kurume, and Masayuki Yamashita*
Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi, Yamashina, Kyoto
607-8414, Japan
Abstract – The first total syntheses of (+)-hostmanin A (1) and
(+)-methyllinderatin (3) were achieved in four steps from a known compound,
1-{2,6-dihydroxy-4-methoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-
cyclohexen-1-yl]phenyl}ethanone (6).
The absolute configuration of
(+)-methyllinderatin (3) was determined. Furthermore, (+)-hostmanin A (1),
which was isolated as an inseparable mixture of hostmanin A and B, was
synthesized as a sole component.
In order to find new antimalarial drugs from plant sources, Fabre and co-workers investigated the
n-hexane extract of Piper hostmannianum (Piperaceae) leaves. As a result, monoterpene-substituted
dihydrochalcones, hostmanin A (1) and B (2), were isolated as an inseparable mixture, as well as a known
compound, (-)-methyllinderatin (3), in 2007 (Figure 1).
(-)-Methyllinderatin (3) exhibited
antiplasmodial activity against both chloroquine-sensitive and resistant strains of Plasmodium falciparum
(F32, FcB1) in vitro, antimalarial activity against Plasmodium vinckei petteri in mice,1 cytotoxicity
towards KB nasopharyngeal carcinoma cells, and antibacterial effects toward Micrococcus luteus.2
(-)-Methyllinderatin (3) has also been isolated from leaves of Piper aduncum (Piperaceae), whereas
(+)-methyllinderatin (3) was isolated from leaves of Lindera umberata (Lauraceae).3
We previously reported the total syntheses of substituted chalcone derivatives, linderol A (4)4,5 and
adunctin E (5) (Figure 2).2,6,7 In a continuation of our synthesis of chalcone derivatives, we planned the
synthesis of methyllinderatin (3) in light of its diverse biological activity. In this paper, we report the
first total syntheses of (+)-methyllinderatin (3) and (+)-hostmanin A (1).

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HETEROCYCLES, Vol. 83, No. 1, 2011
9"
3"
9"
6"
OMe
OMe
8"
8"
OMe
3"
6'
2'
2'
6'
6"
HO
OH
HO
O
1"
7"
1"
7"
1'
1'
HO
O


O
O
O
2
2
1

1

4
4
1
3
(+)-methyllinderatin( )
hostmanin A ( )
2
hostmanin B ( )
Figure 1. Structures of hostmanin A (1), B (2), and tentative structure of (+)-methyllinderatin (3)
OMe
OMe
H
H
H
H
HO
O
HO
O
OH
OH
O
O
4
linderol A ( )
5
adunctin E ( )
Figure 2. Structure of linderol A (4) and proposed structure of adunctin E (5)
The
starting
compound,
1-{2,6-dihydroxy-4-methoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-
cyclohexen-1-yl]phenyl}ethanone (6), was prepared according to the procedure described in the
literature.8 The direct extension of the acetyl group in 6 to a cinnamoyl group by crossed aldol
condensation with benzaldehyde was attempted, but the reaction did not proceed, possibly due to the
existence of two hydroxy groups adjacent to the acetyl group. Thus, 6 was treated with MOMCl in the
presence of potassium carbonate to protect the less hindered hydroxy group selectively to give 7 in 94%
yield. The position of the MOM group was determined by an NOE experiment, which showed
relationships between the aromatic hydrogen at the 5-position and the methyl and methylene groups on
the MOM group in 7 (Scheme 1).
Crossed aldol condensation of monoprotected 7 with benzaldehyde successfully proceeded in the
presence of tert-BuOK as a base (Scheme 2).5 Next, 8 was treated with Et3SiH in the presence of a
catalytic amount of (Ph3P)3RhCl to chemoselectively reduce the conjugated carbon-carbon double bond
of the cinnamoyl group over the isolated double bond.9

HETEROCYCLES, Vol. 83, No. 1, 2011
145
OMe
OMe
H
5
6
R
R
K2CO3, MOMCl
NOE :
acetone
94 %
HO
OH
Me
H3COH2CO
OH
O
Me
O
7
6
Scheme 1. Preparation of 7 and NOE correlations
Finally, the MOM group on 9 was deprotected with 3 N HCl in refluxing methanol for 1.5 h to give two
products together with recovery of 9. The first product was (+)-methyllinderatin (3). The structure of
the synthetic 3 was confirmed by comparison of the spectral data with those of the natural 3 described in
the literature (Tables 1-3).3
Table 1. A comparison of the 1H-NMR data of (+)-synthetic 3 with those of (+)-natural 3
3
3
Position
Natural (270 MHz, CDCl3)
Synthetic (300 MHz, CDCl3)
9',10'-CH3
7"-CH3
0.81, 0.84 (d each, 3H each, J=7.4 Hz)
1.79 (s, 3H)
0.81, 0.84 (d each, 3H each, J=7.0 Hz)
1.79 (s, 3H)


3.00 (t, 2H, J=7.4 Hz)
3.00 (t, 2H, J=7.7 Hz)
3.39 (t, 2H, J=7.4 Hz)
3.79 (s, 3H)
3.39 (t, 2H, J=7.7 Hz)
3.79 (s, 3H)
OCH3
3"-H
3.87 (br d, J=10.4 Hz)
5.46 (s)
3.87 (br d, J=10.6 Hz)
5.46 (s)
2"-H
5'-H
6.05 (s)
7.05 (s)
6.05 (s)
7.05 (s)
OH ( free )
Ph
7.27 (br s, 5H)
13.71 (s)
7.14-7.39 (m, 5H)
OH( chelated )
13.72 (s)
Table 2. A comparison of the 13C-NMR data of (+)-synthetic 3 with those of (+)-natural 3
Natural 3
Synthetic 3
Natural 3
Synthetic 3
Position
Position
(25 MHz, acetone-d6) (75 MHz, acetone-d6)
(25 MHz, acetone-d6) (75 MHz, acetone-d6)

C-1
C-2
C-3
C-4
C-5
C-6
C-1'
C-2'
C-3'
C-4'
142.8
129.1
129.2
126.7
129.2
129.1
105.5
162.1
111.5
163.7
142.9
129.1
129.3
126.9
129.3
129.1
105.5
162.0
111.5
163.9
C-
46.7
31.4
55.8
133.9
126.5
35.9
42.6
23.6
31.4
23.6
46.8
31.3
55.8
133.7
126.6
35.9
42.6
23.6
31.4
23.6

C-
OMe
C-1"
C-2"
C-3"
C-4"
C-5"
C-6"
C-7"
C-5'
C-6'
C=O
91.7
165.2
205.7
91.8
165.2
205.8
C-8"
C-9"
C-10"
29.1
16.7
21.9
29.1
16.6
21.8

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HETEROCYCLES, Vol. 83, No. 1, 2011
Table 3. A comparison of the other data of (+)-synthetic 3 with those of (+)-natural 3
3
3
Synthetic
Data
Natural
IR (CHCl3, cm-1)
3360, 1630, 1590.
408 (M+), 338, 323.
3356, 1624, 1585.
408 (M+), 338, 323.
LRMS m/ z
408.2306
408.2294
HRMS m/z
(M+, calcd for C26H32O4 : 408.2299)
(M+, calcd for C26H32O4 : 408.2300)
 22

[ ]D + 41.0 (c 0.40, CHCl3)
[ ]D + 74.8 (c 0.40, CHCl3)
Specific rotation
Ichino assigned the relative configuration at the 3”- and 4”-positions of (+)-3 as 3”S, 4”S as shown in
Figure 1, and Sticher et al. and Fabre et al. showed those of (-)-3 as 3”R, 4”R based on Ichino’s
representation.1,2 The present total synthesis of (+)-3 indicated the absolute configuration at the 3”- and
4”-positions to be 3”R, 4”R as shown in Scheme 2.
OMe
OMe
PhCHO, t-BuOK
1) Et3SiH, (Ph3P)3RhCl, benzene
7
2) conc HCl, MeOH
67 %
t-BuOH, rt, 3.5h
MOMO
OH
Ph
MOMO
OH
Ph
91 %
O
O
8
9
OMe
conditions:
4"
3"
a) 3N HCl, MeOH, reflux, 1.5h
R
R
conditions
1: 30%, 3: 24%, recovery of 9: 28%
(+)-1
+
HO
OH
[]2D4 + 61.5
(c 0.15, MeOH)
O
b) 3N HCl, MeOH, reflux, 5h
1: 70%
{lit.,3 []D + 41.0 (c 0.40, CHCl3)}
[]2D2 + 74.8 (c 0.40, CHCl3)
(+)-methyllinderatin (3)
Scheme 2. Syntheses of (+)-hostmanin A (1) and (+)-methyllinderatin (3)
The second product was an unexpected byproduct. The byproduct was found to correspond to C26H32O4
by high resolution mass spectrometry (M+; 408.2294). Disappearance of the proton signals on the
double bond and one proton signal from the two phenolic hydroxy groups was observed by comparison of
the H1-NMR spectra of 3 and the byproduct. The byproduct was determined to be (+)-hostmanin A (1)
on the basis of spectral data, which were consistent with the spectral data of natural hostmanin A (1)

HETEROCYCLES, Vol. 83, No. 1, 2011
147
(Tables 4-6).1,10 A longer reaction time improved the yield of (+)-1 to 70% without the formation of
(+)-3.
Table 4. A comparison of the 1H-NMR data of (+)-synthetic 1 with those of natural 1
Position
Natural 1 (500 MHz, CDCl3)a)
Synthetic 1 (300 MHz, CDCl3)
Dihydrochalcone moiety
2-H to 6-H
7.21-7.29 (m, 5H)
7.18-7.29 (m, 5H)


3'-H
-H
3.49 (m, 2H)
3.06 (t, 2H, J=8.0 Hz)
6.02 (s)
3.46 (t, 2H, J=7.8 Hz)
3.03 (t, 2H, J=7.8 Hz)
5.99 (s)
-H
OH (chelated)
4-OCH3
13.90 (s)
3.83 (s, 3H)
13.88 (s)
3.80 (s, 3H)
Monoterpene moiety
2"-Ha
1.74 (m)
1.61 (m)
1.53 (m, 2H)
1.71 (ddd, J=13.8, 2.4, 2.4 Hz)
1.58 (ddd, J=13.8, 13.4, 4.5 Hz)
1.40-1.52 (m, 2H)
2"-Hb
3"-H
4"-Ha
5"-Hb
6"-Ha
6"-Hb
1.21 (m)
3.39. (m)
1.91 (dd, J=13.4, 3.4 Hz)
1.51 (dd, J=13.4, 5.3 Hz)
1.14-1.23 (m)
3.29-3.39 (m)
1.87 (dd, J=13.8, 2.7 Hz)
1.47 (dd, J=13.8, 4.5 Hz)
7"-CH3
8"-H
1.36 (s, 3H)
1.78 (m)
1.33 (s, 3H)
1.79 (qqd, J=6.6, 6.6, 11.1, Hz)
9"-CH3
10"-CH3
1.08 (d, 3H, J=6.8Hz)
0.97 (d, 3H, J=6.8Hz)
1.04 (d, 3H, J=6.6 Hz)
0.94 (d, 3H, J=6.6 Hz)
a) Multiplicity patterns were unclear due to signal overlapping of hostmanin A (1) and B (2). The
ratio of 1 and 2 was 55 to 45.
Table 5. A comparison of the 13C-NMR data of (+)-synthetic 1 with those of natural 1
Natural 1
(125 MHz, CHCl3)
Natural 1
(125 MHz, CHCl3) (75 MHz, CHCl3)
Synthetic 1
(75 MHz, CHCl3)
Synthetic 1
Position
Position

C-1
C-2
C-3
C-4
C-5
C-6
141.8
128.3
128.4
125.8
128.4
128.3
141.7
128.3
128.3
125.8
128.3
128.3
104.6
165.3
91.2
C-
45.5
30.7
55.7
77.9 a)
35.3
20.5
44.0
..
27.2
30.1
45.3
30.6
55.8
76.9
35.2
20.5

C-
OMe
C-1"
C-2"
C-3"
C-1'
C-2'
C-3'
104.7
165.4
91.2
C-4"
C-5"
C-6"
44.0
27.1
30.1
C-4'
C-5'
C-6'
C=O
162.3
106.8
158.9
204.9
162.1
106.8
158.9
204.8
C-7"
C-8"
29.2
26.3
20.9
22.1
29.1
26.2
20.9
22.1
C-9"
C-10"
a) The C-1” position of hostmanin B (2) was assigned as 76.7 ppm.
In conclusion, the first total syntheses of (+)-methyllinderatin (3) and (+)-hostmanin A (1) were achieved
in four steps from the optically pure compound (6). The absolute configuration of (+)-3 was determined
by this synthesis. Furthermore, (+)-hostmanin A (1), which was isolated as an inseparable mixture,

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HETEROCYCLES, Vol. 83, No. 1, 2011
could be prepared as one component. The formation of (+)-1 would suggest that (+)-3 would be the
precursor of 1 in biosynthesis. Efforts to increase the yield of (+)-3 are currently in progress.
Table 6. A comparison of the other data of (+)-synthetic 1 with those of natural 1 and 2
1
2a)
1
Synthetic
Data
Natural and
IR (CHCl3,cm-1)
3425 (chelated OH), 1616, 1585
407 (M - H)+
3550-3000 (chelated OH), 1618, 1587
408 (M+)
LRMS m/ z
407.2242
408.2294
HRMS m/z
([M - H]+, calcd for C26H32O4 : 407.2222)
(M+, calcd for C26H32O4 : 408.2300)
 25
[ ]D - 31.0 (c 0.15, MeOH)
Specific rotation
 24
[ ]D + 61.5 (c 0.15, MeOH)
a) The ratio of hostmanin A (1) and B (2) was 55 to 45.
EXPERIMENTAL
13
NMR spectra were measured on a JEOL AL-300 (1H; 300 MHz, C; 75.5 MHz) and a Varian INOVA
400NB (1H; 400 MHz) for an NOE experiment. IR spectra were taken with a Shimadzu FTIR-8400
spectrophotometer.
A JEOL JMS-GC mate spectrometer and a Shimadzu GCMS-QP5050A
spectrometer were used for low-resolution electron ionization MS (MS) and a JEOL JMS-GC mate
spectrometer was used for high-resolution electron ionization MS (HRMS). Specific rotation was
measued on a JASCO P-2200 polarimeter. All extracts were washed with water and brine, dried over
anhydrous Na2SO4, and evaporated under reduced pressure in the usual work-up procedure. Silica gel
60 (grade 7734, 60 – 230 mesh, Merck) for column chromatography and Silica Gel 60 PF254 (5 – 50 m,
Nacalai tesque) for preparative TLC were used.
2-Hydroxy-4-methoxy-6-methoxymethoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-cyclohexen-1-
yl]acetophenone (7)
To a solution of 6 (400 mg, 1.26 mmol) and MOMCl (303 mg, 3.76 mmol) in distilled acetone (40 mL)
was added K2CO3 (469 mg, 3.39 mmol), and the whole was refluxed for 0.5 h under N2 atmosphere.
After filtration of the K2CO3, the filtrate was evaporated under reduced pressure. The crude product was
purified by silica gel column chromatography (AcOEt：n-hexane = 1：3) to give 7 (428 mg, 94 %). Pale
yellow oil. [  ]D24 + 96.46 (c 1.00, MeOH). 1H-NMR (CDCl3) : 0.77, 0.82 [d each, 3H each, J = 7.0
Hz, (CH3)2CH-], 1.18–1.50 [m, 2H, (CH3)2CH-CH-CH2-], 1.65 [s, 3H, CH3], 1.69-1.79 [m, 1H,
(CH3)2CH-CH-], 1.91-2.23 [m, 3H, (CH3)2CH-CH-CH2-CH2- and (CH3)2CH- ], 2.65 [s, 3H, CH3-C(=O)-],
3.53 [s, 3H, CH3-O-CH2-O-], 3.80 [s, 3H, Ar-OCH3], 3.82-3.90 [m, 1H, Ar-CH-], 5.12 [s, 1H,

HETEROCYCLES, Vol. 83, No. 1, 2011
149
Ar-CH-CH-], 5.27 [s, 2H, CH3-O-CH2-O-], 6.21 [s, 1H, Ar-H], 13.82 [s, 1H, Ar-OH]. 13C-NMR
(CDCl3) : 16.2, 21.6, 22.9, 23.4, 28.5, 30.9, 33.2, 35.3, 41.2, 55.5, 56.5, 88.9, 94.4, 106.2, 113.7, 125.8,
132.0, 159.3, 164.3, 164.3, 203.3. IR (CHCl3) cm-1: 3500 - 3000 (chelated OH), 2932, 1612 (-C=O),
1597. HRMS (EI) m/z: 362.2100 (Calcd for C21H30O5 : 362.2093). LRMS (EI) m/z (rel. int. %): 45
(100), 195 (19), 247 (30), 292 (17), 317 (25), 362 (M+, 9).
(E)-1-{2-Hydroxy-4-methoxy-6-methoxymethoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-
cyclohexen-1-yl]phenyl}-3-phenylprop-2-en-1-one (8)
To a solution of 7 (312 mg, 0.86 mmol) and PhCHO (137 mg, 1.29 mmol) in distilled t-BuOH (12 mL)
was added t-BuOK (193 mg, 1.72 mmol), and the whole was stirred at rt for 3.5 h under N2 atmosphere.
After addition of saturated aqueous NH4Cl solution, the whole was extracted with AcOEt (three times).
The combined organic layers were washed, dried, and evaporated. The crude product was purified by
silica gel column chromatography (AcOEt ： n-hexane = 1 ： 3) to give 8 (352 mg, 91 %).
Orange-yellowish oil. [  ]D25 + 100.56 (c 1.00, MeOH). 1H-NMR (CDCl3) : 0.78, 0.83 [d each, 3H
each, J = 6.8 Hz, (CH3)2CH-], 1.28–1.52 [m, 2H, (CH3)2CH-CH-CH2-], 1.66 [s, 3H, CH3], 1.71-1.81 [m,
1H, (CH3)2CH-CH-], 1.91-2.22 [m, 3H, (CH3)2CH-CH-CH2-CH2- and (CH3)2CH- ], 3.54 [s, 3H,
CH3-O-CH2-O-], 3.82 [s, 3H, Ar-OCH3], 3.84-3.94 [m, 1H, Ar-CH-], 5.15 [s, 1H, Ar-CH-CH-], 5.29 [s,
2H, CH3-O-CH2-O-], 6.22 [s, 1H, Ar-H], 7.33-7.47 [m, 3H, Ph], 7.50-7.66 [m, 2H,Ph], 7.74, 7.87 [d each,
1H each, J = 15.7 Hz, Ar-C(=O)-CH=CH-], 13.65 [s, 1H, Ar-OH]. 13C-NMR (CDCl3) : 16.3, 21.6,
21.7, 23.0, 23.5, 28.5, 30.9, 35.4, 55.6, 56.7, 89.8, 95.2, 114.1, 125.6, 125.8, 127.9, 128.0, 128.1, 128.2,
128.9(2C), 129.9, 132.2, 135.6, 141.6, 158.7, 164.5, 193.2. IR (CHCl3) cm-1: 3500 - 3000 (chelated OH),
2930, 1630 (-C=O), 1611, 1572. HRMS (EI) m/z: 450.2399 (Calcd for C28H34O5 : 450.2406). LRMS
(EI) m/z (rel. int. %): 45 (100), 103 (29), 131(63), 179 (23), 335 (19), 405 (37), 450 (M+, 21).
1-{2-Hydroxy-4-methoxy-6-methoxymethoxy-3-[(1R,6R)-3-methyl-6-(1-methylethyl)-2-cyclohexen-
1-yl]phenyl}-3-phenylpropan-1-one (9)
A solution of 8 (200 mg, 0.44 mmol), Et3SiH (206 mg, 1.77 mmol), and (Ph3P)3RhCl (40 mg) in benzene
(8 mL) was refluxed for 12 h under N2 atmosphere. After cooling, a solution of concd HCl (25 drops) in
MeOH (5 mL) was added to the reaction mixture at rt, and the whole was stirred for additional 2 h.
After addition of saturated aqueous NaHCO3 solution and Et2O, the whole was extracted with Et2O (three
times). The combined organic layers were washed with saturated aqueous NaHCO3 solution, dried, and
evaporated. The crude product was purified by silica gel column chromatography (AcOEt：n-hexane =
1：3) to give 9 (134 mg, 67 %). Pale yellow oil. [  ]D23 + 84.45 (c 1.00, MeOH). 1H-NMR (CDCl3)

150
HETEROCYCLES, Vol. 83, No. 1, 2011
: 0.77, 0.83 [d each, 3H each, J = 6.8 Hz, (CH3)2CH-], 1.28–1.50 [m, 2H, (CH3)2CH-CH-CH2-], 1.65 [s,
3H, CH3], 1.70-1.79 [m, 1H, (CH3)2CH-CH-], 1.90-2.22 [m, 3H, (CH3)2CH-CH-CH2-CH2- and
(CH3)2CH- ], 3.02 [t, 2H, J = 7.8 Hz, Ph-CH2-], 3.35 [t, 2H, J = 7.8 Hz, Ph-CH2-CH2-], 3.47 [s, 3H,
CH3-O-CH2-O-], 3.79 [s, 3H, Ar-OCH3], 3.82-3.92 [m, 1H, Ar-CH-], 5.12 [s, 1H, Ar-CH-CH-], 5.24 [s,
2H, CH3-O-CH2-O-], 6.22 [s, 1H, Ar-H], 7.11-7.36 [m, 5H, Ph], 13.77 [s, 1H, Ar-OH]. 13C-NMR
(CDCl3) : 16.3, 21.5, 22.9, 23.4, 28.5, 30.8, 35.4, 41.2, 45.9, 55.4, 55.5, 56.5, 89.0, 94.3, 94.5, 94.7,
106.0, 113.8, 125.6, 125.9, 128.4(2C), 132.1, 141.7, 159.1, 164.1, 164.3, 204.7. IR (CHCl3) cm-1: 3500
- 3000 (chelated OH), 2932, 1610 (-C=O), 1599. HRMS (EI) m/z: 452.2568 (Calcd for C28H36O5 :
452.2563). LRMS (EI) m/z (rel. int. %): 45 (100), 91 (54), 105(24), 218(21), 337 (22), 407 (43), 452
(M+, 15).
(2S,5R,6S)-3,4,5,6-Tetrahydro-9-hydroxy-7-methoxy-2-methyl-5-(1-methylethyl)-2,6-methano-2H-
1-benzoxocin (1) [(+)-Hostmanin A] and {2,6-Dihydroxy-4-methoxy-3-[(1R,6R)-3-methyl-6-(1-
methylethyl)-2-cyclohexen-1-yl]phenyl}-3-phenylpropan-1-one (3) [(+)-Methyllinderatin]
To a solution of 9 (40 mg, 0.09 mmol) in MeOH (0.5 mL) added 3N HCl (1.0 mL), and the whole was
heated at 100°C for 1.5 h. The reaction mixture was extracted with AcOEt (three times). The
combined organic layers were washed, dried, and evaporated. The crude product was purified by
preparative TLC (AcOEt：n-hexane = 1：3) to give 1 (11 mg, 30 %) as pale yellow oil, 3 (9 mg, 24 %) as
pale yellow oil, and recovery of 9 (11 mg, 28 %).
(+)-Hostmanin A (1)
When the reaction time was prolonged 1.5 h to 5 h at 100°C, only (+)-hostmanin A (1) was obtained in
70% yield.
ACKNOWLEDGEMENTS
This research was supported in part by the 21st Century COE Program, and the “Academic Frontier”
Project for Private Universities, a matching fund subsidy from the Ministry of Education, Culture, Sports,
Science and Technology of Japan (MEXT), a Grant-in-Aid for the Promotion of the Advancement of
Education and Research in Graduate Schools from The Promotion and Mutual Aid Corporation for
Private Schools of Japan, and by a Grant-in-Aid for Scientific Research from the Japan Society for the
Promotion of Science.
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