Syntheses of all stereoisomers of goniodiol from yeast-reduction products and their antimicrobiological activity

Article abstract of DOI:10.1271/bbb.80262

All stereoisomers of goniodiol were synthesized from yeast-reduction products. The C-6 chiral centers were converted from the chiral centers of the yeast-reduction products. Stereoselective conversion of the alkene, which had been prepared from the yeast-reduction product, to glycol constructed the C-7 and C-8 stereochemistry. (+)-Goniodiol and 7-epi-(+)-goniodiol showed the highest antibacterial activity (MIC, 3.1 mM) against Yersinia intermedia.

Full text of DOI:10.1271/bbb.80262

Biosci. Biotechnol. Biochem., 72 (9), 2342–2352, 2008
Syntheses of All Stereoisomers of Goniodiol from Yeast-Reduction Products
and Their Antimicrobiological Activity
y
Takahiro YOSHIDA,1 Satoshi YAMAUCHI,1; Ryosuke TAGO,1 Masafumi MARUYAMA,1
1
Koichi AKIYAMA,2 Takuya SUGAHARA,1 Taro KISHIDA,1 and Yojiro KOBA
1Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan
2Integrated Center for Sciences, Tarumi Station, Ehime University,
3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan
Received April 18, 2008; Accepted June 2, 2008; Online Publication, September 7, 2008
[doi:10.1271/bbb.80262]
All stereoisomers of goniodiol were synthesized from
yeast-reduction products. The C-6 chiral centers were
converted from the chiral centers of the yeast-reduction
products. Stereoselective conversion of the alkene,
which had been prepared from the yeast-reduction
product, to glycol constructed the C-7 and C-8 stereo-
chemistry. (þ)-Goniodiol and 7-epi-(þ)-goniodiol
showed the highest antibacterial activity (MIC, 3.1
mM) against Yersinia intermedia.
Results and Discussion
Synthesis of compounds 1–8
The enantiomeric excess of 11 was determined as
more than 99%ee after the reaction with (ꢀ)-menthyl
chloroformate followed by GC analysis. The cis-lactone
12 was also determined as having more than 99%ee by
reduction to a diol, protection of the primary hydroxy
group as a benzyl ether, and reaction with (ꢀ)-menthyl
chloroformate, followed by HPLC analysis. Olefins 14,
15, 17, and 18 were obtained from compounds 11 and 12
as shown in Scheme 2. The hydroxy group of trans-
hydroxyester 11 was protected as a triisopropylsilyl
ether. Reduction of the resulting ester to an alcohol,
followed by pyridinium chlorochromate oxidation gave
aldehyde 13, which was subjected to a Grignard reaction
and dehydration, giving trans-olefin 14 as a single
isomer. The desilylation of 14 gave hydroxy olefin 15.
Olefins 17 and 18 were prepared from cis-lactone 12.
The reduction of 12 to a diol, this being followed by
protection of the resulting primary hydroxy group as a
trityl ether and of the secondary hydroxy group as a
triisopropyl ether, gave the fully protected compound.
After detritylation, the resulting alcohol was converted
to aldehyde 16 by reduction and oxidation. This alde-
hyde was transformed to trans-alkenes 17 and 18 as a
single isomer by the same method as that already
described above.
Anti and syn additions to olefins 15 and 14 were tried.
Treating olefin 15 with D-fructose-derived ketone 193)
gave an epoxide as a 2:1 mixture of inseparable
diastereomers in 83% yield. Pure stereoisomer 20 was
obtained as the main product after benzoylation,
hydrolysis of the epoxide to a diol under acidic
conditions, followed by protection as an acetonide.
Treatment of olefin 15 with ent-19 gave a 1:3 mixture of
diastereomer in 83% yield. Pure stereoisomer 21 was
obtained from this epoxide as the main product. Stereo-
selective syn addition to olefin 14 was successful by
Key words: goniodiol; yeast-reduction product; antimi-
crobiological activity
6-Substituted 5,6-dihydro-2-pyranone is a well-known
compound which has a wide range of biological activity,
including antimicrobiological activity.1) The relation-
ship between the stereochemistry of 6-substituted 5,6-
dihydro-2-pyranone and its biological activity is un-
known. In this article, a new stereoselective synthetic
route to optically pure (þ)-goniodiol (1), 6-epi-(þ)-
goniodiol (3), 7-epi-(þ)-goniodiol (5), 8-epi-(þ)-gonio-
diol (7), and their enantiomers (2, 4, 6, and 8) is shown,
and the antimicrobiological activity of these eight ster-
eoisomers of goniodiol is then clarified for the first time.
The key reaction for the synthesis of optically pure
(þ)-goniodiol (1), (ꢀ)-goniodiol (2), 6-epi-(þ)-gonio-
diol (3), and the enantiomer of 6-epi-(þ)-goniodiol (4) is
the anti addition of hydroxy groups to olefins 9 and 10
which could be respectively prepared from yeast-
reduction products 11 and 12.2) 7-epi-(þ)-Goniodiol
(5), the enantiomer of 7-epi-(þ)-goniodiol (6), 8-epi-
(þ)-goniodiol (7), and the enantiomer of 8-epi-(þ)-
goniodiol (8) could be obtained by the stereoselective
syn addition of hydroxy groups to olefins 9 and 10
(Scheme 1). The steric configuration at the 6 position of
1, 4, 5 and 7 might be converted from the 1 position of
yeast-reduction product 9, while the steric configuration
of the 6 position of 2, 3, 6 and 8 might be converted
from the 5 position of yeast-reduction product 10.
y
To whom correspondence should be addressed. Tel: +81-89-946-9846; Fax: +81-89-977-4364; E-mail: syamauch@agr.ehime-u.ac.jp

Antimicrobiological Activity of Goniodiol
2343
OH
1
CO2Me
OH
8
11
OH
8
6
7
6
O
O
Ph
7
O
O
Ph
H
H
OH
OH
OR
7-epi-(+)-goniodiol (5)
(+)-goniodiol (1)
Ph
OH
OH
9
6
7
6
7
O
O
8
Ph
O
O
8
Ph
H
H
OH
OH
8-epi-(+)-goniodiol (7)
enantiomer of 6-epi-(+)-goniodiol (4)
OH
OH
6
7
6
7
O
O
8
Ph
H
O
O
8
Ph
OH
OR
H
OH
enantiomer of 7-epi-(+)-goniodiol (6)
Ph
(-)-goniodiol (2)
H
OH
OH
10
6
7
6
7
O
O
Ph
8
O
O
8
Ph
H
H
OH
OH
6-epi-(+)-goniodiol (3)
enantiomer of 8-epi-(+)-goniodiol (8)
O
O
5
12
Scheme 1. Retrosynthetic Analysis of All Stereoisomers of Goniodiol.
employing AD-mix-ꢀ or AD-mix-ꢁ.4) Treatment of
olefin 14 with AD-mix-ꢁ stereoselectively gave glycol
22 as a single isomer in 82% yield. On the other hand,
employment of AD-mix-ꢀ predominantly gave glycol 23
as a single isomer in 92% yield. Basic hydrolysis
followed by pyridinium chlorochromate oxidation of 20
and 21 respectively gave ketones 24 and 25. Protection
as acetonides of 22 and 23, desilylation, and oxidation
gave 26 and 27. Ketones 24–27 were respectively
converted to lactones 28–31 by Baeyer-Villiger oxida-
tion. (þ)-Goniodiol (1) and its stereoisomers 4, 5 and 7
were respectively obtained from lactones 28–31 by the
same method as that described in the literature5)
(Scheme 3). The enantiomeric excess was determined
as more than 99%ee by HPLC analyses employing a
chiral column.
recovering olefin 18 (28%). The stereoselective syn
addition to olefin 17 was also examined. The glycols
were obtained at 40 ꢁC. The treatment of olefin 17 with
AD-mix-ꢀ stereoselectively gave glycol 34 in 36% yield
along with glycol 35 (7%), recovering olefin 17 (41%).
To selectively obtain glycol 35, olefin 17 was treated
with AD-mix-ꢁ, stereoselectively giving glycol 35 in
45% yield along with recovered olefin 17 (33%)
(Scheme 4). The reactivity of the addition reactions to
olefins 17 and 18 was lower than that to olefins 14 and
15. It could be assumed that the protective group closed
to a double bond decreased the reactivity of 14 and 15.
Stereoisomers 2, 3, 6 and 8 were respectively obtained
from 32, 33, 34 and 35 by the same method as that
described for their enantiomers. The enantiomeric
excess was determined as more than 99%ee by HPLC
analyses employing a chiral column.
The reaction of 18 with D-fructose-derived ketone 19
gave stereoisomer 32 as the main product (50%), along
with stereoisomer 33 (7%). Olefin 18 (20%) was
recovered. Stereoisomer 33 was obtained as the main
product by employing ent-19 (32, 15%; 33, 54%),
The stereoselective synthesis of all stereoisomers of
goniodiol having more than 99%ee was accomplished
by using optically pure yeast-reduction products as the
starting material.

2344
T. YOSHIDA et al.
OTIPS
OH
OR
H
a
Ph
b
CHO
CO2Me
H
H
11
13
14: R = TIPS
c
15: R = H
OTIPS
OR
H
O
e
d
Ph
O
CHO
H
H
12
16
17: R = TIPS
18: R = Bz
f
Scheme 2. Preparation of Alkenes from the Yeast-Reducted Product.
(a) (1) TIPSOTf, 2,6-lutidine, CH2Cl2, r.t., 1 h (quantitative yield); (2) LiAlH4, ether, 1 h, 0 ꢁC; (3) PCC, MS 4A, CH2Cl2, r.t., 16 h (82%,
2 steps); (b) (1) PhMgBr, ether, 0 ꢁC, 20 min (90% yield); (2) KHSO4, toluene, reflux, 1.5 h (84% yield); (c) n-Bu4NF, THF, r.t., 4 h (quantitative
yield); (d) (1) ref. 6; (2) TIPSOTf, 2,6-lutidine, CH2Cl2, r.t., 1 h (88% yield); (3) HCO2H, ether, 0 ꢁC, 30 min; (4) K2CO3, MeOH, r.t., 2.5 h
(76% yield, 2 steps); (5) PCC, MS 4A, CH2Cl2, r.t., 16 h (84% yield); (e) (1) PhMgBr, ether, 0 ꢁC, 20 min; (2) KHSO4, toluene, reflux, 1.5 h
(77% yield, 2 steps); (f) (1) n-Bu4NF, THF, r.t., 4 h (99% yield); (2) BzCl, Pyr., CH2Cl2, r.t., 9 h (98% yield).
O
O
OBz
O
O
O
e
g
H
H
O
h
H
H
H
H
(+)-goniodiol (1)
Ph
Ph
O
O
Ph
O
19
O
O
O
O
O
O
a
20
24
28
15
b
O
O
O
O
O
O
O
O
O
e
g
h
enantiomer of
6-epi-(+)-goniodiol (4)
H
Ph
H
Ph
H
Ph
O
O
BzO
O
H
H
H
O
O
O
ent-19
21
25
29
HO
OH
O
O
O
O
TIPSO
f
H
Ph
g
h
Ph
H
O
7-epi-(+)-goniodiol (5)
8-epi-(+)-goniodiol (7)
H
Ph
H
H
O
H
O
c
22
26
30
14
O
O
OTIPS
d
f
O
h
H
Ph
O
g
H
Ph
H
H
Ph
H
H
O
O
O
HO
23
OH
27
31
Scheme 3. Conversion to (þ)-Gonidiol (1) and Its Stereoisomers 4, 5 and 7.
(a) (1) ketone 19, Shi’s conditions, r.t., 18 h (2/1 mixture, 83%); (2) BzCl, Pyr, CH2Cl2, r.t., 16 h (2/1 mixture, 69%); (3) 3 M aq. H2SO4, THF,
r.t., 16 h; (4) CH3C(OCH3)2CH3, p-TsOH, DMF, r.t., 8 h (2 steps; 20, 41%; 21, 21%); (b) ent-19, Shi’s conditions, r.t., 18 h (1/3 mixture, 83%);
(2) BzCl, Pyr, CH2Cl2, r.t., 16 h (2/1 mixture, 70%); (3) 3 M aq. H2SO4, THF, r.t., 16 h; (4) CH3C(OCH3)2CH3, p-TsOH, DMF, r.t., 8 h (2 steps;
20, 20%; 21, 65%); (c) AD-mix-ꢁ, CH3SO2NH2, aq. tert-BuOH, r.t., 47 h (82%); (d) AD-mix-ꢀ, CH3SO2NH2, aq. tert-BuOH, r.t., 4 d (92%);
(e) (1) 2 M aq. NaOH, EtOH, r.t., 14 h (from 20, 97%; from 21, 97%); (2) PCC, MS 4A, CH2Cl2, r.t., 22 h (24, 95%; 25, 91%); (f) (1) 2,2-
dimethoxypropane, p-TsOH, DMF, r.t., 2.5 h (from 22, 89%; from 23, 96%); (2) n-Bu4NF, THF, r.t., 3 h (from 22, 89%; from 23, 92%);
(3) Swern oxidation 70 ꢁC, 2 h, then 0 ꢁC, 0.5 h (26, 98%; 27, 99%); (g) MCPBA, phosphate buffer pH 8, CH2Cl2, 7.5 h (28, 74%; 29, 54%; 30,
77%; 31, 56%); (h) ref. 5.

Antimicrobiological Activity of Goniodiol
2345
O
H
O
O
O
O
O
H
Ph
BzO
O
O
O
H
(-)-goniodiol (2)
H
H
O
Ph
19
H
a
32
18
enantiomer of 24
b
O
H
OBz
H
O
O
O
H
Ph
H
6-epi-(+)-goniodiol (3)
Ph
O
O
O
H
O
ent-19
H
O
O
33
enentiomer of 25
O
OTIPS
H
Ph
H
enantiomer of
7-epi-(+)-goniodiol (6)
H
Ph
H
H
O
O
H
c
HO
OH
34
enantiomer of 26
17
HO
OH
Ph
O
O
d
TIPSO
enantiomer of
8-epi-(+)-goniodiol (8)
H
O
H
Ph
H
H
H
H
enantiomer of 27
35
Scheme 4. Conversion to Stereoisomers 2, 3, 6 and 8.
(a) ketone 19, Shi’s conditions, r.t., 18 h (32, 50%; 33, 7%; recovered 18, 20%); (b) ent-19, Shi’s conditions, r.t., 18 h (32, 15%; 33, 54%;
recovered 18, 28%); (c) AD-mix-ꢀ, CH3SO2NH2, aq. tert-BuOH, 40 ꢁC, 35 h (34, 36%; 35, 7%; recovered 17, 41%); (d) AD-mix-ꢁ,
CH3SO2NH2, aq. tert-BuOH, 40 ꢁC, 35 h (35, 45%; recovered 17, 33%).
Table 1. Antibacterial Activity of (þ)-Goniodiol and Its Stereoisomers (MIC: mM)
1
2
3
4
5
6
7
8
Gram-positive
B. subtilis
S. aureus
>50
>50
50
>50
50
>50
>50
>50
>50
>50
>50
>50
>50
25
>50
50
>50
>50
50
>50
>50
50
L. denitrificans
50
50
Gram-negative
E. coli
25
50
50
50
>50
50
50
>50
>50
>50
>50
>50
50
>50
>50
25
50
>50
50
25
>50
25
50
50
50
25
P. fluorescens
S. choleraesuis
Y. intermedia
3.1
25
12.5
3.1
12.5
12.5
Antimicrobial activity of the stereoisomers of
goniodiol
No antifungal activity against Colletotrichum lage-
narium, Bipolaris oryzae, Fusarium solani, and Alter-
naria altanata, which are phytopathogenic fungi, was
apparent.
bacteria was weak. The stereoisomer which showed the
highest activity against Gram-positive bacteria was
7-epi-(þ)-goniodiol (5), having a 25 mM MIC value
against L. denitrificans. 6-epi-(þ)-Goniodiol (3) and
its enantiomer (4) did not show any activity against
Gram-positive bacteria. On the other hand, all the
compounds showed activity against Gram-negative
bacteria. Y. intermedia being most sensitive to all the
The antibacterial activity of stereoisomers 1–8 is
shown in Table 1. The activity against Gram-positive

2346
T. YOSHIDA et al.
stereoisomers. (þ)-Goniodiol (1) and 7-epi-(þ)-gonio-
diol (5) showed the strongest activity against Y. inter-
media (MIC, 3.1 mM). This fact suggested that the
(6R,8R) structure was more important for higher activity
than the stereochemistry at the 7 position. The activity
of the enantiomer of 6-epi-(þ)-goniodiol (4), which did
not show any activity against Gram-positive bacteria,
was weakest against Y. intermedia (MIC, 50 mM). The
relationship between the stereochemistry of goniodiol
and its antibacterial activity was elucidated for the first
time. Syntheses of the goniodiol derivatives bearing
the stereochemistry of 1 or 5 might be expected to
identify new compounds showing strong antibacterial
activity.
was concentrated. The residue was purified by silica gel
column chromatography (EtOAc/hexane = 7/93) to
give unstable 13 (4.00 g, 0.014 mol, 82%, 2 steps) as a
20
colorless oil. ½ꢀꢂ
¼ þ37 (c 1.0, CHCl3). NMR ꢂH
D
(CDCl3): 1.00–1.11 (21H, m), 1.19 (1H, m), 1.53–1.62
(2H, m), 1.76 (1H, m), 1.85 (1H, m), 1.99 (1H, m), 2.19–
2.29 (2H, m), 2.60 (1H, ddd, J ¼ 19:7, 9.0, 1.9 Hz), 3.90
(1H, ddd, J ¼ 5:8, 5.8, 5.8 Hz), 9.76 (1H, d, J ¼ 1:9 Hz).
NMR ꢂC (CDCl3): 12.5, 18.1, 21.4, 28.8, 34.5, 42.8,
47.8, 79.0, 203.2.
(1R,2S)-1-(trans-Styryl)-2-(triisopropylsilyloxy)cyclo-
pentane (14). To an ice-cooled solution of phenyl-
magnesium bromide (0.15 mol) in ether (100 ml) was
added a solution of 13 (13.6 g, 0.048 mol) in ether
(30 ml). The reaction mixture was stirred for 20 min at
0 ꢁC before additions of sat. aq. NH4Cl solution and
EtOAc. The organic solution was separated, washed
with brine, and dried (Na2SO4). Concentration followed
by silica gel column chromatography (EtOAc/hexane =
7/93) gave benzyl alcohol (15.6 g, 0.043 mol, 90%). To
a refluxing mixture of KHSO4 (4.84 g, 0.036 mol) in
toluene (530 ml) was added a solution of benzyl alcohol
(6.86 g, 0.019 mol) in toluene (40 ml). The reaction
mixture was refluxed for 1.5 h before additions of H2O
and EtOAc. The organic solution was separated, washed
with brine, dried (Na2SO4), and concentrated. The
residue was purified by silica gel column chromatog-
Experimental
Melting point (mp) data are uncorrected. Optical
rotation values were measured by a Horiba SEPA-200
instrument. NMR data were obtained with a JNM-
EX400 spectrometer, and EI and FABMS data were
measured with a JMS-MS700V spectrometer. The silica
gel used was Wakogel C-300 (Wako, 200–300 mesh),
and the HPLC analyses was performed with Shimadzu
LC-6AD and SPD-6AD instruments and a DAICEL
AD-H chiral column (1 ml minꢀ1), with detection at
270 nm.
2-[(1R,2S)-2-(Triisopropylsilyloxy)cyclopentyl]acet-
aldehyde (13). To an ice-cooled solution of 11 (17.1 g,
0.11 mol) and 2,6-lutidine (30.0 ml, 0.26 mol) in CH2Cl2
(150 ml) was added TIPSOTf (34.7 ml, 0.13 mol). The
reaction solution was stirred for 1 h at room temperature
before addition of sat. aq. NaHCO3 solution. The
organic solution was separated, washed with sat. aq.
CuSO4 solution, sat. aq. NaHCO3 solution, and brine,
and dried (Na2SO4). After concentration, the residue
was applied to silica gel column chromatography
raphy (hexane) to give 14 (5.35 g, 0.016 mol, 84%) as a
20
colorless oil, ½ꢀꢂ
¼ þ106 (c 1.0, CHCl3). NMR ꢂH
D
(CDCl3): 1.00–1.09 (21H, m), 1.49 (1H, m), 1.60–1.70
(2H, m), 1.80 (1H, m), 1.87–2.03 (2H, m), 2.59 (1H, m),
4.08 (1H, ddd, J ¼ 5:5, 5.5, 5.5 Hz), 6.12 (1H, dd,
J ¼ 15:8, 8.1 Hz), 6.39 (1H, d, J ¼ 15:8 Hz), 7.17 (1H,
m), 7.23–7.33 (4H, m). NMR ꢂC (CDCl3): 12.3, 18.1,
21.8, 29.7, 35.1, 52.4, 79.5, 126.0, 126.8, 128.4, 129.6,
133.3, 137.9. Anal. Found: C, 76.53; H, 10.55. Calcd. for
C22H36OSi: C, 76.68; H, 10.53%.
(EtOAc/hexane = 1/99) to give TIPS ether (33.8 g,
20
0.11 mol, 100%) as a colorless oil, ½ꢀꢂ
¼ þ37 (c 1.0,
(1S,2R)-2-(trans-Styryl)cyclopentanol (15). To an ice-
cooled solution of 14 (6.46 g, 0.019 mol) in THF (30 ml)
was added n-Bu4NF (24.3 ml, 1 M in THF, 24.3 mmol).
The reaction solution was stirred for 4 h at room
temperature before additions of sat. aq. NH4Cl solution
and EtOAc. The organic solution was separated, washed
with sat. aq. CuSO4 solution, sat. aq. NaHCO3 solution,
and brine, dried (Na2SO4), and evaporated. The residue
was purified by silica gel column chromatography
D
CHCl3). NMR ꢂH (CDCl3): 0.90–1.09 (21H, m), 1.21
(1H, m), 1.56–1.62 (2H, m), 1.73 (1H, m), 1.83 (1H, m),
1.97 (1H, m), 2.10 (1H, dd, J ¼ 14:5, 9.5 Hz), 2.18 (1H,
m), 2.52 (1H, dd, J ¼ 14:5, 4.9 Hz), 3.66 (3H, s), 3.92
(1H, ddd, J ¼ 5:4, 5.4, 5.4 Hz). NMR ꢂC (CDCl3): 12.3,
18.0, 18.1, 21.1, 28.7, 34.2, 37.9, 44.9, 51.4, 78.6, 173.5.
Anal. Found: C, 65.31; H, 11.11. Calcd. for C17H34O3Si:
C, 64.92; H, 10.90%. To an ice-cooled suspension of
LiAlH4 (0.64 g, 0.017 mol) in ether (15 ml) was added a
solution of 13 (5.30 g, 0.017 mol) in ether (30 ml). The
reaction mixture was stirred for 1 h at 0 ꢁC before
additions of sat. aq. MgSO4 solution and K2CO3. The
resulting mixture was stirred at room temperature for
30 min before filtration. Concentration of the filtrate
gave crude alcohol. A reaction mixture of the crude
alcohol, PCC (3.99 g, 0.019 mol), and MS 4A (2.22 g) in
CH2Cl2 (60 ml) was stirred at room temperature for 16 h
before addition of dry ether. After filtration, the filtrate
(EtOAc/hexane = 1/6) to give 15 (3.54 g, 0.019 mol,
20
100%) as a colorless oil, ½ꢀꢂ
¼ þ89 (c 0.9, CHCl3).
D
NMR ꢂH (CDCl3): 1.51 (1H, m), 1.58–1.72 (2H, m),
1.77 (1H, m), 1.88 (1H, br. s), 1.94–2.05 (2H, m), 2.47
(1H, m), 3.94 (1H, ddd, J ¼ 7:0, 7.0, 7.0 Hz), 6.12 (1H,
dd, J ¼ 15:8, 8.2 Hz), 6.45 (1H, d, J ¼ 15:8 Hz), 7.19
(1H, m), 7.24–7.30 (2H, m), 7.34–7.36 (2H, m). NMR
ꢂC (CDCl3): 21.2, 30.0, 33.6, 52.3, 78.6, 126.0, 127.1,
128.5, 130.4, 132.2, 137.3. Anal. Found: C, 83.33; H,
8.65. Calcd. for C13H16O: C, 82.94; H, 8.57%.

Antimicrobiological Activity of Goniodiol
2347
2-[(1S,2S)-2-(Triisopropylsilyloxy)cyclopentyl]acet-
aldehyde (16). cis-Lactone 12 was converted to (1S,2S)-
1.64 (2H, m), 1.72 (1H, m), 1.77–1.83 (2H, m), 1.85–
1.95 (2H, m), 2.58 (1H, m), 4.20 (1H, ddd, J ¼ 4:4, 4.4,
2.3 Hz), 6.33 (1H, dd, J ¼ 16:1, 7.9 Hz), 6.48 (1H, d,
J ¼ 16:1 Hz), 7.21 (1H, m), 7.27–7.30 (2H, m), 7.35–
7.37 (2H, m). NMR ꢂC (CDCl3): 22.1, 28.3, 34.2, 49.3,
75.9, 126.0, 127.1, 128.5, 129.4, 131.6, 137.3. Anal.
Found: C, 82.62; H, 8.47. Calcd. for C13H16O: C, 82.94;
H, 8.57%. To an ice-cooled solution of the resulting
alcohol (3.83 g, 0.020 mol) and pyridine (3.25 ml, 0.040
mol) in CH2Cl2 (20 ml) was added BzCl (2.59 ml,
0.022 mol). The reaction mixture was stirred for 9 h at
room temperature before addition of H2O. The organic
solution was separated, washed with 6 M aq. HCl
solution, sat. aq. NaHCO3 solution, and brine, dried
(Na2SO4), and evaporated. The residue was purified by
silica gel column chromatography (EtOAc/hexane =
2-(2-trityloxyethyl)cyclohexanol.6) The hydroxy group
20
was silylated in 88% yield as a colorless oil, ½ꢀꢂ
¼
D
ꢀ10 (c 1.0, CHCl3). NMR ꢂH (CDCl3): 0.97–1.06 (21H,
m), 1.34 (1H, m), 1.48 (1H, m), 1.52–1.65 (3H, m),
1.66–1.73 (2H, m), 1.87 (1H, m), 1.96 (1H, m), 3.04–
3.14 (2H, m), 4.14 (1H, ddd, J ¼ 7:2, 7.2, 4.2 Hz), 7.19–
7.23 (3H, m), 7.26–7.29 (6H, m), 7.43–7.46 (6H, m).
NMR ꢂC (CDCl3): 12.6, 18.16, 18.21, 21.4, 28.5, 29.6,
34.9, 42.7, 63.0, 75.7, 86.3, 126.8, 127.7, 128.7, 144.6.
Anal. Found: C, 79.44; H, 9.03. Calcd. for C35H48O2Si:
C, 79.49; H, 9.15%. To an ice-cooled solution of trityl
ether (2.80 g, 5.29 mmol) in ether (110 ml) was added
HCO2H (140 ml). The reaction solution was stirred for
30 min at 0 ꢁC before additions of CHCl3 and sat. aq.
NaHCO3 solution. The organic solution was separated,
washed with brine, dried (Na2SO4), and evaporated.
The residue was dissolved in MeOH (30 ml), and then
K2CO3 (2.26 g, 16.4 mmol) was added. The reaction
mixture was stirred for 2.5 h at room temperature. After
concentration of the solvent, the residue was dissolved
in EtOAc and H2O. The organic solution was separated,
washed with brine, dried (Na2SO4), and evaporated.
The residue was applied to silica gel column chromatog-
2/98) to give 18 (5.56 g, 0.020 mol, 100%) as a colorless
20
oil, ½ꢀꢂ
¼ þ131 (c 2.8, CHCl3). NMR ꢂH (CDCl3):
D
1.73 (1H, m), 1.85–2.02 (4H, m), 2.13 (1H, m), 2.84
(1H, m), 5.47 (1H, ddd, J ¼ 5:0, 5.0, 1.7 Hz), 6.31 (1H,
dd, J ¼ 16:0, 7.6 Hz), 6.47 (1H, d, J ¼ 16:0 Hz), 7.15
(1H, m), 7.23–7.28 (4H, m), 7.38–7.42 (2H, m), 7.51
(1H, m), 8.00–8.02 (2H, m). NMR ꢂC (CDCl3): 22.3,
30.1, 32.5, 47.9, 79.4, 126.1, 127.0, 128.3, 128.4, 129.0,
129.5, 130.8, 131.0, 132.7, 137.6, 166.1. Anal. Found:
C, 81.92; H, 6.95. Calcd. for C20H20O2: C, 82.16;
H, 6.89%.
raphy (EtOAc/hexane = 3/97) to give primary alcohol
20
(1.15 g, 4.01 mmol, 76%) as a colorless oil, ½ꢀꢂ
¼
D
ꢀ15 (c 1.0, CHCl3). NMR ꢂH (CDCl3): 1.19–1.25 (21H,
m), 1.41 (1H, br. s), 1.55–1.70 (2H, m), 1.72–1.79 (2H,
m), 1.80–1.94 (3H, m), 1.96–2.09 (2H, m), 3.77–3.90
(2H, m), 4.42 (1H, ddd, J ¼ 3:6, 3.6, 3.6 Hz). NMR ꢂC
(CDCl3): 12.6, 18.1, 18.2, 21.4, 28.7, 32.8, 34.6, 42.5,
62.4, 76.0. Anal. Found: C, 66.87; H, 11.88. Calcd. for
C16H34O2Si: C, 67.07; H, 11.96%. Unstable 16 was
(1S,2S)-2-[(4S,5R)-2,2-Dimethyl-5-phenyl-1,3-dioxo-
lan-4-yl]cyclopentyl benzoate (20) and (1S,2S)-2-[(4R,5S)-
2,2-dimethyl-5-phenyl-1,3-dioxolan-4-yl]cyclopentyl ben-
zoate (21). To a stirred solution of 15 (0.10 g, 0.53
mmol) in CH3CN (2 ml) and dimethoxymethane (3.5 ml)
.
were added buffer solution (0.05 M Na2B4O7 10H2O
obtained from this primary alcohol by PCC oxidation in
20
in aqueous 4 ꢃ 10ꢀ4 M Na2(EDTA) solution, 3.42 ml),
n-Bu4NHSO4 (5 mg, 0.015 mmol), and 19 (50 mg, 0.19
mmol). To the resulting ice-cooled solution was added
a solution of Oxone (0.29 g, 0.47 mmol) in aqueous
Na2(EDTA) (4 ꢃ 10ꢀ4 M, 2.22 ml) solution and a solu-
tion of K2CO3 (0.27 g, 1.95 mmol) in H2O (2.22 ml)
over a period of 1.5 h. The reaction solution was stirred
for 18 h at room temperature, and then EtOAc was
added. The organic solution was separated, washed with
brine, dried (Na2SO4), and evaporated. The residue was
purified by silica gel column chromatography (EtOAc/
hexane = 1/6) to give a diastereomeric mixture (2/1) of
hydroxyepoxides (91 mg, 0.44 mmol, 83%). FABMS
m=z (%): 205 [ðM þ HÞþ, 13], 154 (100), 136 (90),
91 (78). HRMS (FAB) m=z ðM þ HÞþ: Calcd. for
C13H17O2, 205.1229. Found: 205.1230. This hydrox-
yepoxide was benzoylated, giving a diastereomeric
mixture (2/1) of benzoates in 69% yield. Anal. Found:
C, 77.62; H, 6.54. Calcd. for C20H20O3: C, 77.90; H,
6.54%. To an ice-cooled solution of this diastereomeric
mixture of benzoate (90 mg, 0.29 mmol) in THF (1.6 ml)
was added 3 M aq. H2SO4 solution (0.3 ml). The reaction
mixture was stirred for 48 h at room temperature before
additions of H2O and CHCl3. The organic solution was
84% yield as a colorless oil, ½ꢀꢂ
¼ ꢀ12 (c 1.1,
D
CHCl3). NMR ꢂH (CDCl3): 0.97–1.10 (21H, m), 1.45
(1H, m), 1.55 (1H, m), 1.66 (1H, m), 1.73–1.86 (3H, m),
2.29 (1H, m), 2.41 (1H, dd, J ¼ 17:1, 7.7 Hz), 2.77 (1H,
dd, J ¼ 17:1, 6.2 Hz), 4.35 (1H, ddd, J ¼ 4:8, 4.8,
4.8 Hz), 9.76 (1H, s, CHO). NMR ꢂC (CDCl3): 12.3,
17.9, 18.0, 21.2, 28.6, 34.3, 39.5, 44.2, 75.2, 202.3.
(1S,2S)-1-(trans-Styryl)-2-(triisopropylsilyloxy)cyclo-
20
pentane (17). Colorless oil, ½ꢀꢂ
¼ ꢀ5 (c 1.0, CHCl3).
D
NMR ꢂH (CDCl3): 0.94–1.09 (21H, m, iso-Pr), 1.60 (1H,
m), 1.70–1.93 (5H, m), 2.51 (1H, m), 4.35 (1H, ddd,
J ¼ 4:2, 4.2, 4.2 Hz), 6.37 (1H, d, J ¼ 16:0 Hz), 6.44
(1H, dd, J ¼ 16:0, 8.0 Hz), 7.17 (1H, m), 7.25–7.29 (2H,
m), 7.33–7.34 (2H, m). NMR ꢂC (CDCl3): 12.42, 12.44,
18.6, 18.10, 18.15, 18.20, 22.1, 29.8, 35.8, 50.17, 50.23,
126.0, 126.6, 128.4, 129.5, 132.3, 138.1. Anal. Found:
C, 76.87; H, 10.65. Calcd. for C22H36OSi: C, 76.68;
H, 10.53%.
(1S,2S)-2-(trans-Styryl)cyclopentyl benzoate (18).
Desilylation of 17 in 99% yield gave a colorless oil,
20
½ꢀꢂ
¼ þ54 (c 1.6, CHCl3). NMR ꢂH (CDCl3): 1.57–
D

2348
T. YOSHIDA et al.
separated, washed with sat. aq. NaHCO3 solution and
brine, dried (Na2SO4), and evaporated to give crude
glycol. To a solution of the crude glycol in DMF
(0.35 ml) was added 2,2-dimethoxypropane (0.14 ml,
NMR ꢂH (CDCl3): 0.99–1.03 (21H, m), 1.47 (1H, m),
1.52–1.58 (2H, m), 1.60–1.67 (3H, m), 1.79 (1H, m),
2.56 (1H, br. s), 2.73 (1H, br. s), 3.95 (1H, dd, J ¼ 8:0,
2.3 Hz), 4.20 (1H, ddd, J ¼ 6:4, 6.4, 6.4 Hz), 4.46 (1H,
d, J ¼ 8:0 Hz), 7.25–7.35 (5H, m). NMR ꢂC (CDCl3):
12.4, 18.02, 18.04, 22.17, 22.19, 35.4, 49.1, 75.6, 76.4,
77.1, 126.9, 128.1, 128.5, 140.9. Anal. Found: C, 70.04;
H, 10.05. Calcd. for C22H38O3Si: C, 69.79; H, 10.12%.
Reaction with AD-mix-ꢀ. Olefin 14 (2.20 g, 6.38 mmol)
.
1.14 mmol) and p-TsOH H2O (2 mg, 0.011 mmol). The
reaction solution was stirred for 8 h at room temperature
before additions of sat. aq. NaHCO3 solution and
EtOAc. The organic solution was separated, washed
with brine, dried (Na2SO4), and evaporated. The residue
was purified by silica gel column chromatography
(EtOAc/hexane = 3/97) to give 20 (45 mg, 0.12 mmol,
41% from benzoate) as colorless crystals, mp 116–
was treated with AD-mix-ꢀ (7.67 g) for 4 d to give 23
20
(2.22 g, 5.86 mmol, 92%) as a colorless oil, ½ꢀꢂ
¼
D
þ67 (c 0.6, CHCl3). NMR ꢂH (CDCl3): 1.05–1.10 (21H,
m), 1.17 (1H, m), 1.50–1.65 (2H, m), 1.69–1.82 (2H, m),
1.95 (1H, m), 2.10 (1H, m), 3.24 (1H, d, J ¼ 7:3 Hz),
3.78 (1H, ddd, J ¼ 8:8, 2.4, 2.4 Hz), 3.78 (1H, d, J ¼
2:4 Hz), 4.23 (1H, ddd, J ¼ 7:8, 7.8, 7.8 Hz), 4.57 (1H,
dd, J ¼ 7:3, 2.4 Hz), 7.25 (1H, m), 7.32–7.40 (4H, m).
NMR ꢂC (CDCl3): 12.7, 18.05, 18.13, 20.4, 25.3, 34.3,
49.2, 74.8, 79.3, 79.5, 126.3, 127.3, 128.2, 142.5. Anal.
Found: C, 69.83; H, 9.94. Calcd. for C22H38O3Si: C,
69.79; H, 10.12%.
119 ꢁC (MeOH), and 21 (22 mg, 0.060 mmol, 21% from
20
benzoate) as a colorless oil. 20, ½ꢀꢂ
¼ þ6:8 (c 1.0,
D
CHCl3). NMR ꢂH (CDCl3): 0.91 (1H, m), 1.14 (1H, m),
1.43 (3H, s), 1.48–1.58 (2H, m), 1.55 (3H, s), 1.71 (1H,
m), 1.87 (1H, m), 2.12 (1H, m), 4.19 (1H, dd, J ¼ 9:5,
6.6 Hz), 5.22 (1H, d, J ¼ 6:6 Hz), 5.44 (1H, ddd,
J ¼ 3:0, 3.0, 3.0 Hz), 7.20 (1H, m), 7.26–7.32 (2H,
m), 7.35–7.42 (4H, m), 7.53 (1H, m), 7.93–7.95 (2H, m).
NMR ꢂC (CDCl3): 23.2, 24.9, 27.2, 27.8, 32.8, 45.6,
79.69, 79.72, 81.6, 108.2, 127.5, 127.8, 128.06, 128.12,
129.4, 130.9, 132.5, 137.5, 165.8. Anal. Found: C,
(R)-2-[(4S,5R)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]cyclopentanone (24). A reaction solution of 20
(1.05 g, 2.87 mmol) in ethanol (80 ml) and 2 M aq.
NaOH solution (30 ml) was stirred for 14 h at room
temperature before additions of H2O and CHCl3. The
organic solution was separated, washed with brine, dried
(Na2SO4), and evaporated. The residue was purified
by silica gel column chromatography (EtOAc/hexane =
75.02; H, 7.01. Calcd. for C23H26O4: C, 75.38; H,
20
7.15%. 21, ½ꢀꢂ
¼ þ27 (c 1.0, CHCl3). NMR ꢂH
D
(CDCl3): 1.35 (1H, m), 1.43–1.55 (2H, m), 1.48 (3H, s),
1.59–1.62 (2H, m), 1.65 (3H, s), 1.85 (1H, m), 2.04 (1H,
m), 4.58 (1H, dd, J ¼ 7:0, 6.7 Hz), 4.99 (1H, ddd,
J ¼ 3:2, 3.2, 3.2 Hz), 5.28 (1H, d, J ¼ 7:0 Hz), 7.04
(1H, m), 7.15–7.19 (2H, m), 7.26–7.30 (2H, m), 7.35–
7.41 (2H, m), 7.53 (1H, m), 7.82–7.85 (2H, m). NMR ꢂC
(CDCl3): 24.0, 24.6, 26.5, 26.7, 33.1, 46.1, 79.6, 80.1,
80.2, 108.0, 127.0, 127.5, 128.1, 129.5, 130.6, 132.6,
138.1, 166.0. Anal. Found: C, 75.35; H, 7.08. Calcd. for
C23H26O4: C, 75.38; H, 7.15%. Reaction of alcohol 15
with ent-19. Alcohol 15 (0.10 g, 0.53 mmol) was treated
with ent-19 (50 mg, 0.19 mmol), giving a diastereomeric
mixture (1/3) of epoxides (90 mg, 0.44 mmol, 83%).
This diastereomeric mixture of epoxides was converted
to the corresponding diastereomeric mixture of ben-
zoates (96 mg, 0.31 mmol, 70%), and then to acetonide
20 (23 mg, 0.062 mmol, 20%) and acetonide 21 (73 mg,
0.20 mmol, 65%).
1/5) to give alcohol (0.73 g, 2.78 mmol, 97%) as a
20
colorless oil, ½ꢀꢂ
¼ ꢀ44 (c 0.6, CHCl3). NMR ꢂH
D
(CDCl3): 0.77–0.83 (2H, m), 1.36–1.42 (3H, m), 1.48
(3H, s, CH3), 1.53 (1H, m), 1.66 (3H, s, CH3), 1.85 (1H,
m), 2.83 (1H, br. s), 3.99 (1H, ddd, J ¼ 6:8, 6.8, 6.8 Hz),
4.24 (1H, dd, J ¼ 10:3, 6.8 Hz), 5.18 (1H, d, J ¼
6:8 Hz), 7.26–7.33 (5H, m). NMR ꢂC (CDCl3): 20.9,
24.7, 25.7, 27.2, 32.7, 47.4, 78.4, 80.0, 84.5, 108.4,
127.6, 128.0, 128.1, 137.4. Anal. Found: C, 72.87; H,
8.31. Calcd. for C16H22O3: C, 73.25; H, 8.45%. A
reaction mixture of alcohol (0.70 g, 2.67 mmol), PCC
(0.69 g, 3.20 mmol), and MS 4A (0.38 g) in CH2Cl2
(30 ml) was stirred for 22 h at room temperature before
addition of ether. After filtration, the filtrate was
concentrated. The residue was purified by silica gel
column chromatography (EtOAc/hexane = 1/6) to give
(1R,2R)-1-Phenyl-2-[(1R,2S)-2-(triisopropylsilyloxy)-
cyclopent-1-yl]ethane-1,2-diol (22) and (1S,2S)-1-phenyl-
2-[(1R,2S)-2-(triisopropylsilyloxy)cyclopent-1-yl]ethane-
1,2-diol (23). To an ice-cooled solution of AD-mix-ꢁ
(264 mg) and MeSO2NH2 (17 mg, 0.18 mmol) in tert-
BuOH (0.6 ml) and H2O (0.9 ml) was added 14 (60 mg,
0.17 mmol). The reaction mixture was stirred for 47 h at
room temperature before additions of Na2SO3 (0.28 g,
2.22 mmol) and EtOAc. The organic solution was
separated, washed with sat. aq. NaHCO3 solution, brine,
and dried (Na2SO4), and then evaporated. The residue
was purified by silica gel column chromatography
24 (0.66 g, 2.54 mmol, 95%) as colorless crystals, mp
20
63–65 ꢁC (hexane), ½ꢀꢂ
¼ ꢀ4:6 (c 0.9, CHCl3). NMR
D
ꢂH (CDCl3): 1.39–1.46 (2H, m), 1.48 (3H, s, CH3),
1.51–1.62 (2H, m), 1.67 (3H, s), 1.64–1.70 (1H, m),
2.03 (1H, m), 2.27 (1H, ddd, J ¼ 6:0, 6.0, 6.0 Hz), 4.65
(1H, dd, J ¼ 7:8, 6.9 Hz), 5.25 (1H, d, J ¼ 6:9 Hz),
7.27–7.36 (5H, m). NMR ꢂC (CDCl3): 20.2, 24.8, 27.0,
38.3, 50.1, 78.4, 79.5, 108.6, 127.97, 127.99, 128.1,
137.0, 217.9. Anal. Found: C, 73.61; H, 7.58. Calcd. for
C16H20O3: C, 73.82; H, 7.74%. Enantiomer of 24.
(EtOAc/hexane = 1/9) to give 22 (53 mg, 0.14 mmol,
20
Acidic hydrolysis gave 32 in 63% yield as a colorless
20
82%) as a colorless oil, ½ꢀꢂ
¼ þ22 (c 0.7, CHCl3).
oil, ½ꢀꢂ
¼ þ39 (c 1.9, CHCl3). NMR ꢂH (CDCl3):
D
D

Antimicrobiological Activity of Goniodiol
2349
1.53 (1H, m), 1.67–1.80 (4H, m), 1.87–1.97 (2H, m),
3.02 (1H, br. s), 3.65 (1H, br. s), 3.87 (1H, dd, J ¼ 9:6,
3.1 Hz), 4.63 (1H, d, J ¼ 3:1 Hz), 5.53 (1H, m), 7.28–
7.37 (3H, m), 7.42–7.48 (4H, m), 7.59 (1H, m), 8.02–
8.04 (2H, m). NMR ꢂC (CDCl3): 22.0, 25.0, 31.7, 48.6,
74.2, 75.5, 78.9, 127.6, 127.8, 128.2, 128.4, 129.7,
130.0, 133.3, 140.0, 167.4. Anal. Found: C, 73.31; H,
6.70. Calcd. for C20H22O4: C, 73.60; H, 6.79%.
7.33–7.50 (4H, m), 7.56 (1H, m), 7.98–8.00 (2H, m).
NMR ꢂC (CDCl3): 21.8, 26.0, 33.3, 45.8, 74.6, 76.0,
77.8, 127.1, 128.4, 128.5, 129.4, 133.0, 140.4, 165.6.
Conversion to an acetonide gave a mixture with a small
inseparable amount of a by-product in 78% yield. NMR
ꢂH (CDCl3): 1.46 (3H, s), 1.55–1.79 (4H, m), 1.64 (3H,
s), 1.80–1.96 (3H, m), 4.28 (1H, m), 4.63 (1H, dd,
J ¼ 7:3, 6.5 Hz), 5.16 (1H, d, J ¼ 6:5 Hz), 7.25–7.34
(4H, m), 7.40–7.34 (3H, m), 7.57 (1H, m), 8.03 (2H, d,
J ¼ 7:4 Hz). NMR ꢂC (CDCl3): 22.2, 25.1, 27.4, 28.9,
33.7, 45.2, 77.0, 77.5, 79.6, 108.1, 127.5, 128.4, 128.5,
128.6, 129.5, 133.0, 138.2, 165.6. Basic hydrolysis in
Conversion to an acetonide in 87% yield gave colorless
20
crystals, mp 118–120 ꢁC (MeOH), ½ꢀꢂ
¼ þ89 (c 1.7,
D
CHCl3). NMR ꢂH (CDCl3): 0.81 (1H, m), 1.26 (1H, m),
1.29 (3H, s), 1.41 (1H, m), 1.58 (3H, s), 1.62–1.77 (2H,
m), 1.78–1.87 (2H, m), 4.52 (1H, dd, J ¼ 10:5, 6.5 Hz),
5.16 (1H, d, J ¼ 6:5 Hz), 5.54 (1H, m), 7.30–7.38 (5H,
m), 7.42–7.46 (2H, m), 7.55 (1H, m), 8.01–8.03 (2H,
m). NMR ꢂC (CDCl3): 22.4, 24.9, 25.5, 27.3, 32.0, 45.3,
78.7, 79.5, 79.9, 108.2, 127.7, 128.0, 128.1, 128.3,
129.4, 131.1, 132.6, 138.1, 165.7. Anal. Found: C,
75.21; H, 7.04. Calcd. for C23H26O4: C, 75.38; H,
95% yield gave colorless crystals, mp 72–75 ꢁC (hex-
20
ane), ½ꢀꢂ
¼ ꢀ53 (c 1.3, CHCl3). NMR ꢂH (CDCl3):
D
1.36–1.52 (4H, m), 1.48 (3H, s), 1.60–1.70 (4H, m),
1.64 (3H, s), 3.43 (1H, m), 4.66 (1H, dd, J ¼ 6:7,
6.7 Hz), 5.27 (1H, d, J ¼ 6:7 Hz), 7.26–7.34 (3H, m),
7.37–7.39 (2H, m). NMR ꢂC (CDCl3): 22.0,
24.8, 26.3, 27.0, 35.9, 45.5, 74.0, 79.7, 79.8, 107.9,
127.3, 127.8, 128.1, 138.7. Anal. Found: C, 73.18; H,
7.15%. Basic hydrolysis in 99% yield gave colorless
20
crystals, mp 112–115 ꢁC (iso-Pr2O), ½ꢀꢂ
¼ þ82
8.50. Calcd. for C16H22O3: C, 73.25; H, 8.45%. Conver-
20
D
(c 1.1, CHCl3). NMR ꢂH (CDCl3): 0.60 (1H, m), 1.03
(1H, m), 1.25–1.34 (2H, m), 1.49 (3H, s), 1.53–1.72
(3H, m), 1.64 (3H, s), 2.19 (1H, br. s), 4.30 (1H, ddd,
J ¼ 4:3, 4.3, 1.9 Hz), 4.44 (1H, dd, J ¼ 10:4, 6.6 Hz),
5.22 (1H, d, J ¼ 6:6 Hz), 7.26–7.33 (5H, m). NMR ꢂC
(CDCl3): 23.0, 25.2, 25.8, 27.4, 33.7, 45.8, 75.0, 79.8,
80.6, 108.2, 127.4, 127.9, 128.1, 137.6. Anal. Found: C,
sion to a ketone gave 98% yield, ½ꢀꢂ
¼ ꢀ138 (c 0.8,
D
CHCl3).
(R)-2-[(4R,5R)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]cyclopentanone (26). Conversion of 22 to an aceto-
20
nide in 89% yield gave a colorless oil, ½ꢀꢂ
¼ þ28
D
(c 1.1, CHCl3). NMR ꢂH (CDCl3): 0.94–0.98 (21H, m),
1.45–1.51 (1H, m), 1.48 (3H, s), 1.53 (3H, s), 1.61 (1H,
m), 1.73–1.87 (5H, m), 4.06 (1H, dd, J ¼ 9:0, 1.8 Hz),
4.13 (1H, ddd, J ¼ 6:2, 6.2, 6.2 Hz), 4.54 (1H, d,
J ¼ 9:0 Hz), 7.30 (1H, m), 7.33–7.36 (4H, m). NMR ꢂC
(CDCl3): 12.2, 17.9, 21.8, 22.0, 27.07, 27.14, 35.4, 46.9,
76.5, 81.5, 82.3, 108.5, 126.7, 128.1, 128.4, 137.7. Anal.
Found: C, 71.74; H, 10.12. Calcd. for C25H42O3Si: C,
72.95; H, 8.39. Calcd. for C16H22O3: C, 73.25; H,
20
8.45%. Conversion to ketone gave 81% yield, ½ꢀꢂ
¼
D
þ4:9 (c 0.8, CHCl3).
(R)-2-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]cyclopentanone (25). Basic hydrolysis of 21 in 97%
20
yield gave a colorless oil, ½ꢀꢂ
¼ þ82 (c 0.8, CHCl3).
D
NMR ꢂH (CDCl3): 0.44 (1H, br. s), 1.42–1.51 (5H, m),
1.46 (3H, s), 1.60–1.70 (2H, m), 1.63 (3H, s), 3.65 (1H,
m), 4.29 (1H, dd, J ¼ 7:4, 7.1 Hz), 5.28 (1H, d,
J ¼ 7:1 Hz), 7.31 (1H, m), 7.36–7.41 (4H, m). NMR
ꢂC (CDCl3): 23.2, 24.7, 27.0, 27.6, 35.0, 49.6, 75.9,
79.6, 80.6, 108.0, 127.3, 128.1, 128.4, 138.2. Anal.
Found: C, 73.09; H, 8.35. Calcd. for C16H22O3: C,
71.70; H, 10.12%. Desilylation in 89% yield gave a
20
colorless oil, ½ꢀꢂ
¼ þ24 (c 1.1, CHCl3). NMR ꢂH
D
(CDCl3): 1.47–1.51 (1H, m), 1.47 (3H, s), 1.55 (3H, s),
1.63–1.66 (2H, m), 1.71 (1H, m), 1.76 (1H, br. s), 1.79–
1.87 (3H, m), 3.96 (1H, ddd, J ¼ 6:1, 6.1, 6.1 Hz), 3.99
(1H, dd, J ¼ 8:8, 3.4 Hz), 4.62 (1H, d, J ¼ 8:8 Hz),
7.25–7.38 (5H, m). NMR ꢂC (CDCl3): 22.2, 24.4, 27.08,
27.14, 35.0, 47.6, 75.6, 81.4, 83.2, 108.4, 126.9, 128.3,
128.5, 137.7. Anal. Found: C, 72.84; H, 8.44. Calcd. for
C16H22O3: C, 73.24; H, 8.46%. PCC oxidation in 82%
73.24; H, 8.46%. PCC oxidation in 91% yield gave a
20
colorless oil, ½ꢀꢂ
¼ þ138 (c 1.0, CHCl3). NMR ꢂH
D
(CDCl3): 1.36 (1H, m), 1.46 (3H, s), 1.42–1.52 (1H, m),
1.64 (3H, s), 1.68–1.89 (3H, m), 2.01 (1H, ddd,
J ¼ 18:6, 10.1, 8.5 Hz), 2.14 (1H, ddd, J ¼ 18:4, 8.5,
2.4 Hz), 4.86 (1H, dd, J ¼ 7:5, 2.4 Hz), 5.39 (1H, d,
J ¼ 7:5 Hz), 7.27 (1H, m), 7.32–7.36 (4H, m). NMR ꢂC
(CDCl3): 20.7, 24.1, 24.4, 26.2, 38.0, 50.0, 77.9, 79.0,
108.2, 126.5, 127.6, 128.1, 138.6, 219.5. Anal. Found:
C, 72.43; H, 7.74. Calcd. for C16H20O3: C, 73.82; H,
7.74%. Enantiomer of 25. Acidic hydrolysis of 33 gave
a mixture with a small inseparable amount of a by-
product in 72% yield. NMR ꢂH (CDCl3): 1.52–1.70 (2H,
m), 1.73 (1H, m), 1.78–1.89 (2H, m), 1.90–2.05 (2H,
m), 2.37 (1H, br. s), 2.61 (1H, br. s), 4.17 (1H, m), 4.69
(1H, d, J ¼ 4:5 Hz), 5.40 (1H, br. s), 7.28–7.32 (3H, m),
yield gave colorless crystals, mp 97–101 ꢁC (EtOH),
20
½ꢀꢂ
¼ þ93 (c 1.2, CHCl3). NMR ꢂH (CDCl3): 1.47
D
(3H, s), 1.54 (3H, s), 1.80 (1H, m), 2.07–2.23 (5H, m),
2.29 (1H, m), 4.26 (1H, dd, J ¼ 9:1, 1.6 Hz), 4.63 (1H,
d, J ¼ 9:1 Hz), 7.26–7.36 (5H, m). NMR ꢂC (CDCl3):
20.8, 22.7, 26.9, 27.1, 38.5, 47.3, 80.8, 81.1, 109.0,
126.6, 128.5, 128.6, 136.8, 218.2. Anal. Found: C,
73.64; H, 7.65. Calcd. for C16H20O3: C, 73.82; H,
7.74%. Enantiomer of 26. Conversion of 34 to an
20
acetonide in 85% yield gave a colorless oil, ½ꢀꢂ
¼
D
þ4:3 (c 1.2, CHCl3). NMR ꢂH (CDCl3): 0.89–0.95 (21H,
m, iso-Pr), 1.45 (1H, m), 1.48 (3H, s, CH3), 1.54 (3H, s,
CH3), 1.63–1.78 (4H, m), 1.90–2.01 (2H, m), 4.12 (1H,

2350
T. YOSHIDA et al.
ddd, J ¼ 7:0, 7.0, 7.0 Hz, CHOSi), 4.26 (1H, dd,
J ¼ 8:9, 2.1 Hz, CH(OR)CH(OR)Ph), 4.52 (1H, d,
J ¼ 8:9 Hz, CH(OR)Ph), 7.24–7.36 (5H, m, ArH).
NMR ꢂC (CDCl3): 12.2, 17.92, 17.94, 21.1, 22.7, 27.2,
27.3, 34.4, 41.7, 75.1, 80.9, 82.2, 108.6, 127.1, 128.0,
128.3, 138.2. Anal. Found: C, 71.69; H, 10.07. Calcd.
J ¼ 8:9, 2.4 Hz), 5.40 (1H, d, J ¼ 8:9 Hz), 7.29–7.37
(3H, m), 7.43–7.44 (2H, m). NMR ꢂC (CDCl3): 21.0,
26.7, 27.2, 28.3, 39.9, 46.0, 78.9, 84.0, 108.8, 127.0,
128.3, 128.5, 137.2, 218.5. Anal. Found: C, 73.70;
H, 7.71. Calcd. for C16H20O3: C, 73.82; H, 7.74%.
Enantiomer of 27. Conversion of 35 to an acetonide
20
for C25H42O3Si: C, 71.70; H, 10.12%. Desilylation in
20
in 94% yield gave a colorless oil, ½ꢀꢂ
¼ ꢀ4:7 (c 1.9,
D
99% yield gave a colorless oil, ½ꢀꢂ
¼ ꢀ4:8 (c 0.6,
CHCl3). NMR ꢂH (CDCl3): 1.06–1.11 (21H, m), 1.29
(1H, m), 1.42–1.49 (2H, m), 1.47 (3H, s), 1.52 (3H, s),
1.54–1.66 (3H, m), 1.81 (1H, m), 4.19 (1H, dd, J ¼ 9:0,
8.9 Hz), 4.53 (1H, m), 4.58 (1H, d, J ¼ 8:9 Hz), 7.29–
7.35 (3H, m), 7.38–7.40 (2H, m). NMR ꢂC (CDCl3):
12.7, 18.1, 18.2, 21.8, 24.6, 27.3, 27.6, 34.6, 50.3,
75.1, 81.9, 83.7, 108.3, 128.2, 128.28, 128.33, 138.2.
Anal. Found: C, 71.68; H, 10.23. Calcd. for C25H42O3Si:
D
CHCl3). NMR ꢂH (CDCl3): 1.50 (3H, s, CH3), 1.59 (3H,
s, CH3), 1.62–1.69 (3H, m), 1.80 (1H, m), 1.87–1.99
(3H, m), 2.39 (1H, d, J ¼ 3:4 Hz, OH), 4.11–4.14 (2H,
m, CH(OR)CH(OR)Ph, CHOH), 4.66 (1H, d, J ¼ 8:8
Hz, CH(OR)Ph), 7.32–7.38 (5H, m, ArH). NMR ꢂC
(CDCl3): 21.7, 22.9, 27.0, 27.3, 35.0, 44.1, 75.4, 82.1,
83.0, 109.2, 126.8, 128.6, 128.7, 137.2. Anal. Found: C,
73.18; H, 8.53. Calcd. for C16H22O3: C, 73.25; H,
8.45%. Conversion to a ketone. To a solution of oxalyl
chloride (0.22 ml, 2.60 mmol) in CH2Cl2 (13 ml) was
added DMSO (0.24 ml, 3.38 mmol) in CH2Cl2 (1 ml) at
ꢀ70 ꢁC. The mixture was stirred for 10 min at ꢀ70 ꢁC,
and then a solution of alcohol (0.33 g, 1.26 mmol) in
CH2Cl2 (4 ml) was added. The resulting reaction solu-
tion was stirred for 2 h at ꢀ70 ꢁC before addition of
Et3N (1.29 ml, 9.26 mmol). The resulting mixture was
stirred for 30 min at 0 ꢁC before additions of sat. aq.
NH4Cl solution and EtOAc. The organic solution was
separated, washed with brine, dried (Na2SO4), and
evaporated. The residue was purified by silica gel
C, 71.70; H, 10.12%. Desilylation in 86% gave a
20
colorless oil, ½ꢀꢂ
¼ ꢀ4:1 (c 0.5, CHCl3). NMR ꢂH
D
(CDCl3): 1.22 (1H, m), 1.43 (1H, m), 1.47–1.54 (1H,
m), 1.52 (3H, s), 1.57 (3H, s), 1.67 (1H, m), 1.70–1.81
(2H, m), 1.91 (1H, m), 2.62 (1H, br. s), 4.03 (1H,
dd, J ¼ 8:4, 7.9 Hz), 4.48 (1H, m), 4.74 (1H, d, J ¼
8:4 Hz), 7.30–7.40 (5H, m). NMR ꢂC (CDCl3): 22.6,
26.2, 27.3, 27.4, 34.4, 46.9, 74.5, 83.6, 83.8, 108.9,
127.6, 128.6, 137.6; FABMS m=z (%): 263 [ðM þ HÞþ,
25%], 205 (89), 187 (55), 148 (66), 119 (64), 91 (100).
HRMS (FAB) m=z ðM þ HÞþ: Calcd. for C16H23O3,
263.1647. Found: 263.1650. Conversion to a ketone by
20
Swern oxidation gave 99% yield, ½ꢀꢂ
¼ ꢀ3:4 (c 0.6,
D
column chromatography (EtOAc/hexane = 5/95) to
20
CHCl3).
give a ketone (0.32 g, 1.23 mmol, 98%), ½ꢀꢂ
¼ ꢀ92
D
(c 1.8, CHCl3).
(R)-6-[(4S,5R)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]tetrahydropyran-2-one (28). A reaction mixture of 24
(0.51 g, 1.96 mmol) and MCPBA (70%, 0.96 g, 3.92
mmol) in CHCl3 (20 ml) and phosphate buffer (20 ml,
pH 8) was stirred for 7.5 h at room temperature before
addition of sat. aq. Na2S2O3 solution. The organic
solution was separated, washed with sat. aq. NaHCO3
solution and brine, dried (Na2SO4), and evaporated.
The residue was purified by silica gel column chroma-
tography (EtOAc/hexane = 1/4) to give 28 (0.40 g,
1.45 mmol, 74%) as colorless crystals, mp 128–131 ꢁC,
(R)-2-[(4S,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]cyclopentanone (27). Conversion of 23 to an aceto-
20
nide in 96% yield gave a colorless oil, ½ꢀꢂ
¼ þ12
D
(c 0.8, CHCl3). NMR ꢂH (CDCl3): 0.99 (1H, m), 1.00–
1.10 (21H, m), 1.42 (1H, m), 1.47 (3H, s), 1.53 (3H, s),
1.61–1.67 (3H, m), 1.71 (1H, m), 2.17 (1H, m), 3.71
(1H, dd, J ¼ 8:0, 7.1 Hz), 4.43 (1H, m), 4.73 (1H, d,
J ¼ 8:0 Hz), 7.27–7.36 (3H, m), 7.39–7.41 (2H, m).
NMR ꢂC (CDCl3): 12.5, 18.15, 18.17, 23.2, 27.15,
27.19, 27.3, 35.7, 50.7, 75.9, 82.6, 84.7, 108.3, 127.5,
128.2, 128.4, 138.7. Anal. Found: C, 71.69; H, 10.10.
20
20
½ꢀꢂ
¼ ꢀ53 (c 0.9, CHCl3) (½ꢀꢂ
¼ ꢀ52 (c 0.5,
D
D
CHCl3) in the literature).5) The NMR data agree with
those in the literature.5) Enantiomer of 28, ½ꢀꢂ
(c 0.9, CHCl3).
20
Calcd. for C25H42O3Si: C, 71.70; H, 10.12%. Desilyla-
20
¼ þ53
D
tion in 92% yield gave a colorless oil, ½ꢀꢂ
¼ þ42
D
(c 0.8, CHCl3). NMR ꢂH (CDCl3): 0.82 (1H, m), 1.44–
1.53 (1H, m), 1.50 (3H, s, CH3), 1.54–1.59 (2H, m), 1.55
(3H, s), 1.64 (1H, m), 1.87–1.95 (2H, m), 2.80 (1H,
br. s), 3.79 (1H, dd, J ¼ 8:3, 8.3 Hz), 4.09 (1H, ddd,
J ¼ 7:3, 7.3, 7.3 Hz), 4.69 (1H, d, J ¼ 8:3 Hz), 7.28–
7.37 (3H, m), 7.39–7.41 (2H, m). NMR ꢂC (CDCl3):
21.6, 26.4, 27.18, 27.22, 33.3, 49.4, 77.4, 83.6, 87.2,
108.9, 127.6, 128.4, 137.5. Anal. Found: C, 73.23; H,
8.58. Calcd. for C16H22O3: C, 73.24; H, 8.46%.
(R)-6-[(4R,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]tetrahydropyran-2-one (29). 54% yield, colorless
20
crystals, mp 78–81 ꢁC, ½ꢀꢂ
¼ ꢀ58 (c 0.5, CHCl3).
D
NMR ꢂH (CDCl3): 1.48 (3H, s, CH3), 1.57–1.62 (2H,
m), 1.65 (3H, s, CH3), 1.76–1.86 (2H, m), 2.30–2.33
(2H, m, CH2(C=O)O), 3.84 (1H, ddd, J ¼ 10:5, 7.1,
3.3 Hz, CHOC=O), 4.40 (1H, dd, J ¼ 7:1, 7.1 Hz,
CH(OR)CH(OR)Ph), 5.39 (1H, d, J ¼ 7:1 Hz, CH(OR)Ph),
7.27–7.30 (2H, m, ArH), 7.33–7.39 (3H, m, ArH). NMR
ꢂC (CDCl3): 17.8, 24.3, 24.4, 26.6, 29.3, 78.1, 79.2,
79.4, 108.9, 127.2, 128.0, 128.1, 137.0, 170.4. Anal.
Found: C, 69.42; H, 7.32. Calcd. for C16H20O4: C,
Conversion to a ketone in 67% yield gave a colorless
20
oil, ½ꢀꢂ
¼ þ3:5 (c 0.8, CHCl3). NMR ꢂH (CDCl3):
D
1.42 (3H, s), 1.54 (3H, s), 1.74 (1H, m), 1.93 (1H, m),
2.07–2.10 (2H, m), 2.21–2.24 (3H, m), 3.85 (1H, dd,

Antimicrobiological Activity of Goniodiol
2351
20
69.54; H, 7.29%. Enantiomer of 29, ½ꢀꢂ
(c 1.0, CHCl3).
¼ þ58
8-epi-(þ)-Goniodiol (7). 68% yield. The NMR data
20
D
agree with those in the literature.10) ½ꢀꢂ
¼ ꢀ13 (c 0.5,
D
25
CHCl3) (lit.:11) ½ꢀꢂD ¼ ꢀ13:7 (c 0.8, CHCl3)). >99%ee
(R)-6-[(4R,5R)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]tetrahydropyran-2-one (30). 77% yield with a small
inseparable amount of by-product. NMR ꢂH (CDCl3):
1.51 (3H, s, CH3), 1.56 (3H, s, CH3), 1.72 (1H, m), 1.84
(1H, m), 1.87–2.02 (2H, m), 2.42 (1H, ddd, J ¼ 17:9,
8.9, 7.0 Hz, CHH(C=O)O), 2.57 (1H, ddd, J ¼ 17:9,
5.7, 5.7 Hz, CHH(C=O)O), 4.03 (1H, dd, J ¼ 7:8,
5.2 Hz, CH(OR)CH(OR)Ph), 4.42 (1H, m, O=COCH),
4.97 (1H, d, J ¼ 7:8 Hz, CH(OR)Ph), 7.29–7.39 (3H, m,
ArH), 7.43–7.45 (2H, m, ArH). NMR ꢂC (CDCl3): 18.2,
23.8, 26.9, 27.1, 29.7, 79.7, 80.2, 83.8, 110.0, 128.4,
128.5, 138.0, 170.3.
(HPLC, 20% iso-PrOH in hexane, tR 13.1 min). Enan-
20
tiomer of 8-epi-(þ)-goniodiol (8). ½ꢀꢂ
¼ þ13 (c 1.0,
D
CHCl3), >99%ee (HPLC, 20% iso-PrOH in hexane,
tR 15.2 min).
(1S,2R)-2-[(1R,2R)-1,2-Epoxy-2-phenyleth-1-yl]cy-
clopentyl benzoate (32) and (1S,2R)-2-[(1S,2S)-1,2-
epoxy-2-phenyleth-1-yl]cyclopentyl benzoate (33). Ole-
fin 18 (63 mg, 0.22 mmol) was treated with 19 (45 mg,
0.13 mmol) at room temperature for 18 h, giving 32
(35 mg, 0.11 mmol, 50%) and 33 in (5 mg, 0.016 mmol,
7%). Olefin 18 (13 mg, 0.045 mmol, 20%) was recov-
20
ered. 32, colorless oil, ½ꢀꢂ
¼ þ41 (c 1.5, CHCl3).
D
(R)-6-[(4S,5S)-2,2-Dimethyl-5-phenyl-1,3-dioxolan-4-
yl]tetrahydropyran-2-one (31). 56% yield, colorless oil,
NMR ꢂH (CDCl3): 1.72 (1H, m), 1.80 (1H, m), 1.84–
1.99 (3H, m), 2.03–2.15 (2H, m), 3.15 (1H, dd, J ¼ 7:3,
2.0 Hz), 3.71 (1H, d, J ¼ 2:0 Hz), 5.60 (1H, ddd,
J ¼ 5:1, 5.1, 2.3 Hz), 7.19–7.21 (2H, m), 7.24–7.31
(3H, m), 7.38–7.42 (2H, m), 7.53 (1H, m), 7.97–7.99
(2H, m). NMR ꢂC (CDCl3): 22.1, 25.9, 32.6, 46.8, 57.3,
61.7, 77.4, 125.5, 128.0, 128.27, 128.34, 129.5, 130.6,
132.8, 137.4, 165.9. Anal. Found: C, 77.85; H, 6.62.
Calcd. for C20H20O3: C, 77.90; H, 6.54%. Olefin 18
(70 mg, 0.24 mmol) was treated with ent-19 (50 mg,
0.19 mmol), giving 32 (11 mg, 0.036 mmol, 15%) and
epoxide 33 (41 mg, 0.13 mmol, 54%). Olefin 18 was
20
½ꢀꢂ
¼ ꢀ49 (c 1.0, CHCl3). NMR ꢂH (CDCl3): 1.51
D
(3H, s, CH3), 1.58 (3H, s, CH3), 1.70–1.87 (3H, m), 2.02
(1H, m), 2.50 (1H, ddd, J ¼ 18:0, 8.5, 6.8 Hz, CHHC=
O), 2.59 (1H, ddd, J ¼ 18:0, 5.8, 5.8 Hz, CHHC=O),
3.75 (1H, dd, J ¼ 8:7, 1.4 Hz, CH(OR)CH(OR)Ph),
4.31 (1H, m, CHOC=O), 5.18 (1H, d, J ¼ 8:7 Hz,
CH(OR)Ph), 7.31–7.43 (5H, m, ArH). NMR ꢂC (CDCl3):
18.3, 25.4, 26.5, 27.3, 29.9, 75.5, 78.0, 84.8, 109.8,
126.8, 128.5, 128.7, 137.2, 170.9. Anal. Found: C, 69.30;
H, 7.22. Calcd. for C16H20O4: C, 69.54; H, 7.29%. Enan-
20
tiomer of 31, ½ꢀꢂ
¼ þ49 (c 0.9, CHCl3).
recovered (20 mg, 0.068 mmol, 28%). 33, colorless oil,
20
D
½ꢀꢂ
¼ þ63 (c 0.9, CHCl3). NMR ꢂH (CDCl3): 1.71
D
20
(þ)-Goniodiol (1). ½ꢀꢂ
¼ þ75 (c 1.4, CHCl3) (lit.5)
(1H, m), 1.88–2.00 (4H, m), 2.14 (1H, m), 2.20 (1H, m),
3.07 (1H, dd, J ¼ 6:7, 2.0 Hz), 3.66 (1H, d, J ¼ 2:0 Hz),
5.56 (1H, ddd, J ¼ 6:1, 6.1, 3.9 Hz), 7.13–7.16 (2H, m),
7.20–7.22 (3H, m), 7.28–7.32 (2H, m), 7.48 (1H,
m), 7.84–7.86 (2H, m). NMR ꢂC (CDCl3): 22.2, 26.9,
32.4, 45.8, 57.8, 62.7, 77.7, 125.6, 127.9, 128.20,
128.23, 129.5, 130.2, 132.8, 137.2, 166.2. Anal. Found:
C, 78.15; H, 6.71. Calcd. for C20H20O3: C, 77.90;
H, 6.54%.
D
20
½ꢀꢂ
¼ þ71:4 (c 0.74, CHCl3)), >99%ee (HPLC, 20%
D
iso-PrOH in hexane, tR 7.5 min). (ꢀ)-Goniodiol (2).
20
½ꢀꢂ
¼ ꢀ75 (c 1.8, CHCl3), >99%ee (HPLC, 20%
D
iso-PrOH in hexane, tR 9.7 min).
Enantiomer of 6-epi-(þ)-goniodiol (4). 75% yield,
20
colorless crystals, mp 142–145 ꢁC, ½ꢀꢂ
¼ þ47 (c 0.7,
D
20
CHCl3) (lit.:7) ½ꢀꢂ
¼ þ43:0 (c 0.64, CHCl3)). The
D
NMR data agree with those in the literature.7) >99%ee
(HPLC, 20% iso-PrOH in hexane, tR 11.1 min). 6-epi-
(1S,2S)-1-Phenyl-2-[(1S,2S)-2-(triisopropylsilyloxy)-
cyclopent-1-yl]ethane-1,2-diol (34) and (1R,2R)-1-phenyl-
2-[(1S,2S)-2-(triisopropylsilyloxy)cyclopent-1-yl]ethane-
1,2-diol (35). Olefin 17 was converted to 34 (36%) and
35 (7%) at 40 ꢁC for 35 h by employing AD-mix-ꢀ.
20
(þ)-Goniodiol (3), ½ꢀꢂ
¼ ꢀ48 (c 0.2, CHCl3) (lit.:
D
20
½ꢀꢂ
¼ ꢀ47 (c 0.3, CHCl3)),8) >99%ee (HPLC, 20%
D
iso-PrOH in hexane, tR 8.4 min).
7-epi-(þ)-Goniodiol (5). 70% yield, colorless oil,
Olefin 17 was recovered (41%). 34, colorless crystals,
20
20
20
½ꢀꢂ
¼ þ80 (c 0.2, MeOH) (lit.:9) ½ꢀꢂ
¼ þ85:4
mp 68–71 ꢁC (iso-Pr2O). ½ꢀꢂ
¼ þ14 (c 0.7, CHCl3).
D
D
D
(c 0.3, MeOH)). The NMR data in C5D5N agree with
those in the literature.9) The NMR ꢂH (CDCl3): 2.49 (1H,
ddd, J ¼ 18:8, 5.2, 4.9 Hz), 2.60 (1H, m), 2.91 (1H, br. s),
3.10 (1H, br. s), 3.94 (1H, m), 4.41 (1H, ddd, J ¼ 10:9,
5.5, 5.2 Hz), 4.90 (1H, d, J ¼ 4:2 Hz), 5.99 (1H, dd,
J ¼ 9:7, 1.0 Hz), 6.92 (1H, m), 7.31–7.38 (5H, m). NMR
ꢂC (CDCl3): 24.9, 71.9, 76.1, 77.3, 120.9, 126.4, 128.3,
128.7, 140.2, 145.7, 163.9. >99%ee (HPLC, 10% iso-
NMR ꢂH (CDCl3): 1.07–1.13 (21H, m), 1.42 (1H, m),
1.54–1.65 (3H, m), 1.72 (1H, m), 1.79 (1H, m), 2.06
(1H, m), 3.36 (1H, br. s), 3.91 (1H, br. s), 4.13 (1H, d,
J ¼ 8:9 Hz), 4.32 (1H, ddd, J ¼ 4:6, 4.6, 4.6 Hz), 4.51
(1H, d, J ¼ 8:9 Hz), 7.28–7.38 (5H, m). NMR ꢂC
(CDCl3): 12.4, 17.96, 18.04, 22.2, 22.6, 36.4, 43.6,
76.0, 78.41, 78.44, 127.3, 128.0, 128.4, 140.4. Anal.
Found: C, 69.40; H, 9.90. Calcd. for C22H38O3Si: C,
69.79; H, 10.12%. Olefin 17 was converted to glycol 35
PrOH in hexane, tR 24.0 min). Enantiomer of 7-epi-(þ)-
20
goniodiol (6), ½ꢀꢂ
¼ ꢀ80 (c 0.9, MeOH), >99%ee
as a colorless oil by using AD-mix-ꢁ at 40 ꢁC for 35 h in
D
20
(HPLC, 10% iso-PrOH in hexane, tR 21.8 min).
45% yield, ½ꢀꢂ
¼ þ13 (c 1.0, CHCl3). NMR ꢂH
D

2352
T. YOSHIDA et al.
(CDCl3): 1.08–1.16 (21H, m), 1.53 (1H, m), 1.59 (1H,
m), 1.74–1.83 (5H, m), 3.41 (1H, br. s), 3.84 (1H, ddd,
J ¼ 5:7, 5.7, 5.7 Hz), 4.07 (1H, d, J ¼ 6:1 Hz), 4.65–
4.69 (2H, m), 7.27 (1H, m), 7.33–7.39 (4H, m). NMR ꢂC
(CDCl3): 12.7, 18.07, 18.14, 21.2, 26.0, 35.0, 44.9, 75.9,
77.1, 77.2, 126.7, 127.6, 128.4, 141.9. Anal. Found:
C, 69.73; H, 10.21. Calcd. for C22H38O3Si: C, 69.79;
H, 10.12%.
Acknowledgments
The 400 MHz NMR data were measured at INCS,
Ehime University. We thank the staff at this center for the
MS measurements, and are also grateful to Marutomo
Co. (Iyo, Ehime, Japan) for financial support.
References
Organisms. Bacillus subtilis subsp. subtilis NBRC
13719T, Pseudomonas fluorescens NBRC 14160T, and
Staphylococcus aureus subsp. aureus NBRC 14462
were purchased from National Institute of Technology
and Evaluation (NITE), Biological Resource Center,
Japan. Escherichia coli JCM 1649, Listeria denitrificans
JCM 11481, Salmonella choleraesuis subsp. cholerae-
suis JCM 6977 and Yersinia intermedia JCM 7579 were
obtained from Institute of Physical and Chemical
Research (RIKEN), Japan.
1) Davies-Coleman, M. T., and Rivett, D. E. A., Naturally
occurring 6-substituted 5,6-dihydro-ꢀ-pyrones. Fortschr.
Chem. Org. Naturst., 55, 1–35 (1989).
2) Yamauchi, S., Takeda, K., Ganaha, M., and Kinoshita,
Y., Synthesis of (R)-6,7-dihydro-5-HETE lactone and
(S)-6,7-dihydro-5-HETE lactone by using novel yeast
reduction as a key reaction. J. Chem. Soc., Perkin Trans.
1, 2156–2160 (2002).
3) Wang, Z. X., Tu, Y., Frohn, M., Zhang, J. R., and Shi,
Y., An efficient catalytic asymmetric epoxidation
method. J. Am. Chem. Soc., 119, 11224–11235 (1997).
4) Sharpless, K. B., Amberg, W., Bennani, Y. L., Crispino,
G. A., Hartung, J., Jeong, K.-S., Kwong, H.-L.,
Morikawa, K., Wang, Z.-M., Xu, D., and Zhang, X.-L.,
The osmium-catalyzed asymmetric dihydroxylation: a
new ligand class and a process improvement. J. Org.
Chem., 57, 2768–2771 (1992).
5) Tate, E. W., Dixon, D. J., and Ley, S. V., A highly
enantioselective total synthesis of (þ)-goniodiol. Org.
Biomol. Chem., 4, 1698–1706 (2006).
6) Yamauchi, S., Kinoshita, Y., and Kinoshita, Y., New
method for synthesizing the intermediate to 5-HETE
from yeast-mediated reduction products by employing
Baeyer-Villiger oxidation with complete retention of
enantiomer excess. Biosci. Biotechnol. Biochem., 67,
1959–1969 (2003).
7) Nakashima, K., Kikuchi, N., Shirayama, D., Miki, T.,
Ando, K., Sono, M., Suzuki, S., Kawase, M., Kondoh,
M., Sato, M., and Tori, M., Total synthesis and cyto-
toxicity of (þ)- and (ꢀ)-goniodiol and 6-epi-goniodiol.
Construction of ꢀ,ꢁ-unsaturated lactone by ring-closing
metathesis. Bull. Chem. Soc. Jpn., 80, 387–394 (2007).
8) Banwell, M. G., Coster, M. J., Karunaratne, O. P., and
Smith, J. A., A chemoenzymatic synthesis of the
styryllactone (þ)-goniodiol from naphthalene. J. Chem.
Soc., Perkin Trans. 1, 1622–1624 (2002).
9) Mu, Q., Tang, W., Li, C., Lu, Y., Sun, H., Zheng, H.,
Hao, X., Zheng, Q., Wu, N., Lou, L., and Xu, B., Four
new styryllactones from Goniothalamus leiocarpus.
Heterocycles, 51, 2969–2976 (1999).
10) Ramachandran, P. V., Chandra, J. S., and Reddy,
M. V. R., Stereoselective syntheses of (þ)-goniodiol,
(ꢀ)-8-epigoniodiol, and (þ)-9-deoxygoniopypyrone via
alkoxyallylboration and ring-closing metathesis. J. Org.
Chem., 67, 7547–7550 (2002).
11) Tsubuki, M., Kanai, K., Nagase, H., and Honda, T.,
Stereocontrolled syntheses of novel styryl lactones,
(þ)-goniodiol, (þ)-goniotriol, (þ)-8-acetylgoniotriol,
(þ)-goniofufurone, (þ)-9-deoxy-goniopypyrone, (þ)-
goniopypyrone, and (þ)-altholactone, from common
intermediates and cytotoxicity of their congeners. Tetra-
hedron, 55, 2493–2514 (1999).
Antibiotic spectra of (þ)-goniodiol and its stereo-
isomers. The ability of each compound to inhibit the
growth of a variety of Gram-positive and Gram-negative
bacterial strains was assessed by the paper disc method,
the minimum inhibitory concentration (MIC) was
determined for those strains that showed sensitivity to
the tested compounds. The paper disc test used agar
plates containing Nissui nutrient broth (Nissui Pharma-
ceutical Co., Ltd.) A 100 ml of an exponential culture
of each respective strain was made into molten agar
containing the nutrient broth. After the agar had
solidified, a paper disc containing 15 ml of 50 mM of
the tested compound was put on to the agar plate. The
plate was incubated for 24 h at 30 ꢁC (L. denitrificans
and P. fluorescens) or at 37 ꢁC (B. subtilis, S. aureus,
E. coli, S. choleraesuis and Y. intermedia), and the
diameter of any halo of inhibition around the paper
disc was measured. The MIC value was determined
from a two-fold dilution series for any strain that showed
a halo of inhibition.
Fungal strains and culture conditions. The phytopa-
thogenic fungi, Colletotrichum lagenarium, Bipolaris
oryzae, Fusarium solani, and Alternaria altanata, had
been isolated from a farm at Ehime University and were
kindly presented by Dr. Ohguchi. Each fungus was
cultured on potato dextrose agar (PDA, Sigma-Aldrich,
Canada).
Antifungal assay. The paper disc method was adopted
for the first screening. Briefly, fungal mycelia were
spotted on the center of the PDA plate (’100-mm dish)
and incubated at 28 ꢁC until the colony diameter became
4–5 cm. A paper disc soaked in dimethyl sulfoxide
containing a test chemical was placed at the edge of
the colony. The growth inhibition was observed after
culturing at 28 ꢁC for 7–10 d.