Total syntheses of (-)- and (+)-boronolide and their plant growth-inhibitory activity

Article abstract of DOI:10.1271/bbb.120317

Optically pure (+)- and (-)-boronolides were stereoselectively synthesized from yeast reductive products which had been obtained by yeast reduction of one common racemic substrate. The lactone structure of boronolide was constructed by Baeyer-Villiger oxi

Full text of DOI:10.1271/bbb.120317

Biosci. Biotechnol. Biochem., 76 (9), 1708–1714, 2012
Total Syntheses of (ꢀ)- and (þ)-Boronolide
and Their Plant Growth-Inhibitory Activity
y
Satoshi YAMAUCHI,1;2; Yasuyoshi ISOZAKI,1 Hiroki NISHIMURA,1
1
Tomoko TSUDA,1 Hisashi NISHIWAKI,1 and Yoshihiro SHUTO
1Faculty of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime 790-8566, Japan
2South Ehime Fisheries Research Center, 1289-1 Funakoshi, Ainan, Ehime 798-4292, Japan
Received April 23, 2012; Accepted May 21, 2012; Online Publication, September 7, 2012
[doi:10.1271/bbb.120317]
Optically pure (þ)- and (ꢀ)-boronolides were stereo-
selectively synthesized from yeast reductive products
which had been obtained by yeast reduction of one
common racemic substrate. The lactone structure of
boronolide was constructed by Baeyer-Villiger oxida-
tion. The stereochemistry of the yeast reduction prod-
ucts was studied to obtain the stereocenters at 5
positions of the dodecanolides of (þ)- and (ꢀ)-borono-
lides. The stereochemistry of the 6 and 7 positions was
obtained by AD-mix-ꢀ or ꢁ oxidation. The chiral center
at the 8 position was constructed by employing (R)-(þ)-
or (S)-(ꢀ)-2-methyl-CBS-oxazaborolidine reduction or
the Mitsunobu reaction. The plant growth-inhibitory
activity against Echinochloa crusgalli L. of naturally
occurring (þ)-boronolide was higher than that of the
(ꢀ)-boronolide.
O
O
1
O
H
OAc
1
O
OAc
5
8
5
6
8
6
7
7
H
OAc
OAc
OAc
OAc
(+)-boronolide (1)
(-)-boronolide (2)
O
O
O
O
OAc
O
O
O- -D-glucosyl
parasorbic acid
psilotin
cryptocaryalactone
Fig. 1. (þ)- and (ꢀ)-Boronolides and Plant Growth-Inhibiting 6-
Substituted 5,6-Dihydro-ꢀ-pyrone Compounds.
Key words: boronolide; plant growth-inhibitory activity;
6-substituted 5,6-dihydro-ꢀ-pyrone; yeast
reduction
The retrosynthetic analysis is outlined in Scheme 1.
The chiral carbons at the 5-positions of (þ)- and (ꢀ)-
boronolides could respectively be converted from the 1
and 5 positions of yeast reductive products 3 and 4,8)
which were obtained from a common racemate. The
lactone rings could be constructed by Baeyer-Villiger
oxidation to cyclopentanone derivatives which could be
obtained from 5 and 6. The stereochemistry of the 6 and
7 positions could respectively be constructed by AD-
mix-ꢁ and ꢀ oxidations9) to olefins 5 and 6. The 8
positions would then be obtained by respective alkyla-
tion to aldehydes 7 and 8. Aldehyde 7 could then be
transformed from diol 9 which had previously been
obtained from yeast reductive product 3 in our labo-
ratory.10) The Aldehyde 8 could be obtained from 10
which had also previously been prepared from yeast
reductive product 4.10) The ꢀ,ꢁ-unsaturated olefin of 7
would be introduced by the Wittig reaction to the
aldehyde derived from primary alcohol 9, using
ClPh3CH2OCH3 followed by elimination. Aldehyde 8
could also be obtained after converting 10 to the
enantiomer of 9.
(þ)-Boronolide (1),1,2) which has been synthesized by
many research groups,3–6) comprises 6-substituted 5,6-
dihydro-ꢀ-pyrone bearing a polyacetoxy side chain
(Fig. 1). Many compounds bearing a similar structure
have been reported and characterized as having wide-
ranging biological activity.7) Although the extracts
containing (þ)-boronolide has been used as a folk
medicine, the biological activity of (þ)-boronolide has
not been elucidated. Neither the isolation nor synthetic
study of (ꢀ)-boronolide (2) has been reported. Stimu-
lated by the apparent biological activity, total syntheses
of (þ)- and (ꢀ)-boronolides and a biological study were
the objectives of this project. This article describes a
new synthetic route to (þ)-boronolide, the first synthesis
of (ꢀ)-boronolide, and their plant growth-regulatory
activity. The plant growth-regulatory activity of one of
the enantiomers of parasorbic acid, psilotin, and crypto-
caryalactone (Fig. 1) have been identified in the course
of biological research into 6-substituted 5,6-dihydro-ꢀ-
pyron.7) However, the optical purity of the isolated 6-
substituted 5,6-dihydro-ꢀ-pyrone has not been reported.
This present study is the first attempt to clarify the
biological activity of both enantiomers by using the
optically pure 6-substituted 5,6-dihydro-ꢀ-pyrone com-
pound.
Results and Discussion
The development of diol 9 is depicted in Scheme 2.
After selectively protecting the primary hydroxy group
as a trityl ether, the secondary hydroxy group was
converted to a triisopropylsilyl ether. Selective cleavage
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

(ꢀ)- and (þ)-Boronolide
1709
OR1
OR1
OH
OH
OR2
O
OMOM
OH
1
(+)-boronolide (1)
(CH2)3CH3
H
CO2Me
5
7
9
3
OR1
OR1
OH
OR2
O
O
(-)-boronolide (2)
OTr
O
(CH2)3CH3
H
5
6
8
10
4
Scheme 1. Retrosynthetic Analysis of (þ)- and (ꢀ)-Boronolides.
OH
OTIPS
OTIPS
OTIPS
OMOM
O
OH
OH
a
b
OH
+
H
(CH2)3CH3
(CH2)3CH3
9
11
12
13
OTIPS
O
c
d
e
(CH2)3CH3
13
12
14
OR2
O
OR1
OBn
OAc
OBn
OTIPS
OBn
j
g
f
(CH2)3CH3
(CH2)3CH3
13
(CH2)3CH3
H
H
OR1
OAc
19
15
16: R1 = H, R2 = TIPS
17: R1 = Ac, R2 = TIPS
18: R1 = Ac, R2 = H
h
i
O
O
H
OAc
k
m
(+)-boronolide (1)
(CH2)3CH3
OAc
OR
20: R = Bn
21: R = Ac
l
Scheme 2. Synthesis of (þ)-Boronolide.
(a) (1) TrCl, pyridine, r.t., 2 h, 73% yield; (2) TIPSOTf, 2,6-lutidine, CH2Cl2, r.t., 2 h, 84% yield; (3) HCO2H, ether, ꢀ5 ꢁC, 15 min, 71%
yield; (4) PCC, MS 4A, CH2Cl2, r.t., 16 h, 88% yield; (5) ClPh3PCH2OCH3, KHMDS, ꢀ70 ꢁC, 30 min, and then r.t., 1 h, 92% yield; (6) 50%
CH3CO2H in THF, r.t., 110 h, 99% yield. (b) n-BuLi, THF, ꢀ70 ꢁC, 1 h, 12: 63% yield, 13: 27% yield. (c) PCC, MS 4A, CH2Cl2, r.t., 12 h, 91%
yield. (d) (R)-(þ)-2-methyl-CBS-oxazaborolidine, catecholborane, ꢀ70 ꢁC, 1 h, 61% yield (recovery of 14, 30%). (e) (1) Ph3P, p-nitrobenzoic
acid, DEAD, THF, r.t., 4 h; (2) 1 M aq. NaOH, EtOH, r.t., 3 h, 60% yield (2 steps). (f) MgO, 2-benzyloxymethylpyridinium triflate,
benzotrifluoride, 85 ꢁC, 72 h, 60% yield (recovery of 13, 38%). (g) AD-mix-ꢁ, methanesulfonamide, aq. tert-BuOH, r.t., 76 h, 75% yield.
(h) Ac2O, DMAP, pyridine, r.t., 18 h, 91% yield. (i) HF-pyridine, THF, r.t., 22 h, 93% yield. (j) PCC, MS 4A, CH2Cl2, r.t., 16 h, 85% yield.
(k) MCPBA, Na2HPO4–NaH2PO4 buffer, CHCl3, r.t., 16 h, 50% yield (recovery of 19, 42%). (l) (1) H2, 20% Pd(OH)2/C, EtOAc, ambient
temperature, 7 h; (2) pyridine, Ac2O, DMAP, r.t., 8 h, 96% yield. (m) reference 14.
of the trityl group and subsequent oxidation by pyridi-
nium chlorochromate of the resulting primary hydroxy
group gave the corresponding aldehyde. This aldehyde
was subjected to the Wittig reaction by using
ClPh3CH2OCH3 and potassium bis(trimethylsilyl)amide,
and then the resulting enol ether was treated with acetic
acid to give trans-ꢀ,ꢁ-unsaturated aldehyde 11 as a
single isomer. The reaction of this aldehyde 11 with
n-butyl lithium gave undesired R-alcohol 12 (63%) and
desired S-alcohol 13 (27%). Applying the R- and S-
Mosher reagent to 12 and 13 were ineffective to
determine their stereochemistry. However, the stereo-
chemistry of 12 and 13 could be assumed by the (R)- and
(S)-CBS reduction. After converting alcohol 12 to
ketone 14 by oxidation, the resulting ketone was
exposed to (R)-(þ)-2-methyl-CBS-oxazaborolidine,11)
giving the same product as 13 as a single stereoisomer
in 61% yield. On the other hand, treating ketone 14 with
(S)-(ꢀ)-2-methyl-CBS-oxazaborolidine gave the same
product as 12 as a single stereoisomer in 80% yield.
Undesired R-alcohol 12 was converted to desired S-
alcohol 13 by employing the Mitsunobu reaction
followed by hydrolysis in 60% yield. Benzylation of
the secondary hydroxy group of 13 under the basic or
Lewis acid condition was troublesome due to decom-
position, however, benzyl ether 15 was obtained in the
moderate yield under the neutral condition using 2-
benzyloxymethylpyridinium triflate.12) This intermediate
was then carried through the stage where the two chiral
centers were constructed. The exposure of 15 to AD-
mix-ꢁ gave desired glycol 16 in 75% yield, together
with an undesired glycol (17%). The desilylation of 17
was then attempted after acetylation. The application of
HF/pyridine allowed clean deprotection of the triiso-
propylsilyl group without any by-products, which were
caused by treating with tetra-n-butylammonium fluoride.
Resulting cyclopentanol derivative 18 was oxidized to
cyclopentanone derivative 19 by using pyridinium
chlorochromate. The oxygen atom of the lactone was
introduced by Baeyer-Villiger oxidation, employing

1710
S. YAMAUCHI et al.
OH
OBz
OTIPS
OMOM
a
c
d
OTr
OR
OTr
10
24
22: R = Tr
b
23: R = H
OTIPS
O
OTIPS
OH
OTIPS
O
e
H
(CH2)3CH3
(CH2)3CH3
25
26
27
OTIPS
OR
OBn
f
(CH2)3CH3
(-)-boronolide (2)
H
OR
28: R = H
29: R = Ac
g
Scheme 3. Synthesis of (ꢀ)-Boronolide (2).
(a) (1) MsCl, Et3N, CH2Cl2, r.t., 1 h; (2) BzONa, DMSO, 60 ꢁC, 30 h, 50% yield (2 steps). (b) PPTS, MeOH, reflux, 4 h, 75% yield. (c) (1)
PCC, MS 4A, CH2Cl2, r.t., 16 h, 76% yield; (2) TIPSOTf, DBU, DMAP, CH2Cl2, r.t., 3 h, 100% yield; (3) OsO4, NMO, aq. acetone, tert-BuOH,
r.t., 20 h; NaBH4, EtOH, r.t., 4 h, 71% yield (2 steps); (4) TrCl, pyridine, r.t., 16 h, 94% yield; (5) MOMCl, iso-Pr2NEt, CH2Cl2, r.t., 16 h; (6) 1 M
aq. NaOH, EtOH, 60 ꢁC, 12 h; (7) TIPSOTf, 2,6-lutidine, r.t., 2 h, 85% yield (3 steps). (d) see Scheme 2. (e) (S)-(ꢀ)-2-methyl-CBS-
oxazaborolidine, catecholborane, ꢀ70 ꢁC, 1 h, 63% yield. (f) (1) MgO, 2-benzyloxymethylpyridinium triflate, benzotrifluoride, 85 ꢁC, 72 h, 65%
yield; (2) AD-mix-ꢀ, methanesulfonamide, aq. tert-BuOH, r.t., 76 h, 81% yield. (g) Ac2O, DMAP, pyridine, r.t., 18 h, 89% yield.
Table 1. Plant Growth-Inhibitory Activity of (þ)- and (ꢀ)-Borono-
m-chloroperbenzoic acid, giving lactone 20. Baeyer-
Villiger oxidation did not proceed when the cyclo-
pentanone derivative bearing a triacetoxy side chain was
used as a substrate. Benzyl ether was selected as one of
the protective groups for this reason. The hydrogenolysis
of 20 by using Pd(OH)2/C under H2 gas and subsequent
acetylation led to known intermediate 21. Intermediate
21 synthesized in this study exhibited 1H- and 13C-NMR
spectra indistinguishable from those previously reported
for 21.13) Finally, an ꢀ,ꢁ-unsaturated double bond
was introduced to lactone 21 by reacting with
[PhSe(O)]2O14) to give 1. The NMR data and optical
rotation value of our synthetic 1 were in agreement with
those of natural 1.5)
As depicted Scheme 3, the synthesis of (ꢀ)-borono-
lide began with converting 10,10) which had been
prepared from another yeast reductive product, to ꢀ,ꢁ-
unsaturated aldehyde 25. After converting the secondary
hydroxy group of 10 to a mesylate, treating with sodium
benzoate afforded a benzoate with inversion of the
configuration. The cis-cyclopentane isomer of 29 was
obtained from 10 without inverting the configuration.
Many by-products were observed due to migration of the
acetyl group by applying the cis-cyclopentane derivative
at the stage of desilylation to give a cyclopentanol
derivative. Faced with this problem, configuration
inversion was achieved at the first stage to give 22.
Cleavage of the trityl ether and subsequent oxidation
gave the corresponding aldehyde. This aldehyde was
transformed to a glycol by ꢀ-hydroxylation and sub-
sequent reduction. Protections of the respective primary
and secondary hydroxy groups as a trityl ether and
methoxymethyl ether, and subsequent hydrolysis and
silylation gave corresponding fully protected compound
24. After deprotecting the primary hydroxy group, the
resulting alcohol was converted to 25 by the same
method as that described for the preparation of 11, and
then the (ꢀ)-boronolide was obtained from 25 according
to the synthetic method described for the (þ)-borono-
lide at 1 mM (growth %)
(þ)-Boronolide (ꢀ)-Boronolide
Lolium multiflorum Lam.: Shoot
80% ꢂ 12
52% ꢂ 9:3
100% ꢂ 7:3
102% ꢂ 8:4
109% ꢂ 7:66
78% ꢂ 9:4
wase-fudo
Lactuca sativa L.:
green-wave
Root
Shoot
Root
125% ꢂ 9:63
121% ꢂ 8:11
lide. (S)-(ꢀ)-2-Methyl-CBS-oxazaborolidine reduction
was applied to 26 to construct the stereochemistry at the
8-position of the (ꢀ)-boronolide, giving 27. AD-mix-ꢀ
was employed to olefin 27 after benzylation to obtain 28.
The enantiomeric excess of both the (þ)- and (ꢀ)-
boronolides was determined as more than 99% by using
a chiral column. The enantiomeric excess of the
synthesized (þ)-boronolide had not been described in
the previous reports.
The plant growth-regulatory activity of the (þ)- and
(ꢀ)-boronolides was next evaluated (Table 1). (þ)-
Boronolide, which is a natural component, depressed the
root growth of Italian ryegrass (Lolium multiflorum
Lam.) at 1 mM. The activity of the unnatural (ꢀ)-
boronolide was weaker than that of the (þ)-boronolide.
Weak activity of (þ)-boronolide against shoot growth
was also observed. Although the plant growth-inhibitory
activity of some other 6-substituted 5,6-dihydro-ꢀ-
pyrones has been reported (Fig. 1), the activity of their
enantiomers has not previously been reported. The plant
growth inhibitory activity of (þ)-boronolide against
plant growth was therefore discovered for the first time,
and the activity was compared with its enantiomer from
this present study. Neither the (þ)- nor (ꢀ)-boronolide
affected the growth of Lactuca sativa L.
In summary, a new synthetic route to optically pure
(þ)-boronolide was developed, and the first synthesis of
optically pure (ꢀ)-boronolide was achieved by employ-
ing two yeast reduction products from one common
racemic compound. This enabled us to compare the

(ꢀ)- and (þ)-Boronolide
1711
(1R,2S)-2-(2-Trityloxyeth-1-yl)cyclopentyl benzoate (22). To an
ice-cooled solution of alcohol 10 (20.2 g, 54.2 mmol) and Et3N
(8.30 mL, 59.5 mmol) in CH2Cl2 (20 mL) was added MsCl (4.60 mL,
59.4 mmol). The reaction mixture was stirred at room temperature for
1 h before addition of H2O. The organic solution was separated, and
dried (Na2SO4). After concentration of the solvent, the residue was
dissolved in DMSO (400 mL). To this solution was added BzONa
(39.2 g, 272 mmol), and then the reaction mixture was stirred at 60 ꢁC
for 30 h before additions of H2O and EtOAc. The organic solution was
separated, washed with brine, and dried (Na2SO4). Concentration
followed by silica gel column chromatography (5% EtOAc in hexane)
biological activity of both enantiomers, revealing the
plant growth-inhibitory activity of the (þ)-boronolide.
This result is valuable information in the field of
chemical ecology.
Experimental
General experimental procedures. Optical rotations values were
measured with a Horiba SEPA-200 instrument, and IR data were
measured with a Horiba FT-720 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). HPLC analyses were
performed with Shimadzu LC-6AD and SPD-6AV instruments.
gave benzoate 22 (12.9 g, 27.1 mmol, 50%, 2 steps) as a colorless oil,
20
½ꢀꢃ
ꢀ31 (c 0.6, CHCl3). 1H-NMR (CDCl3) ꢂ: 1.20 (1H, m), 1.56
D
(1H, m), 1.62–1.77 (3H, m), 1.84–1.94 (2H, m), 2.05 (1H, m), 2.22
(1H, m), 3.07–3.18 (2H, m), 4.98 (1H, m), 7.16–7.27 (11H, m), 7.40–
7.43 (6H, m), 7.54 (1H, m), 7.99 (2H, d, J ¼ 8:8 Hz). 13C-NMR
(CDCl3) ꢂ: 22.6, 30.1, 31.8, 33.8, 42.5, 62.4, 82.0, 86.5, 126.8, 127.7,
128.2, 128.6, 129.5, 130.7, 132.7, 144.4, 166.3; IR ꢃmax (CHCl3): 2960,
1709 cmꢀ1. Anal. Found: C, 83.06; H, 6.85%. Calcd. for C33H32O3:
C, 83.16; H, 6.77%.
E-3-[(1R,2S)-2-(Triisopropylsilyloxy)cyclopent-1-yl]propenal (11).
A solution of diol 9 (8.80 g, 46.3 mmol) and TrCl (12.9 g, 46.3 mmol)
in pyridine (14 mL) was stirred at room temperature for 2 h before
additions of H2O and EtOAc. The organic solution was separated,
washed with sat. aq. CuSO4, sat. aq. NaHCO3, and brine, and dried
(Na2SO4). Concentration followed by silica gel column chromatog-
raphy (EtOAc/hexane = 1/6) gave hydroxy trityl ether as a mixture of
diastereomers (14.6 g, 33.8 mmol, 73%). Anal. Found: C, 77.38; H,
7.43%. Calcd. for C28H32O4: C, 77.75; H, 7.46. To an ice-cooled
solution of hydroxy trityl ether (14.6 g, 33.8 mmol) and 2,6-lutidine
(10.8 mL, 92.4 mmol) in CH2Cl2 (100 mL) was added TIPSOTf
(9.50 mL, 35.3 mmol). The reaction solution was stirred at room
temperature for 2 h before addition of sat. aq. NaHCO3 solution. The
organic solution was separated, washed with sat. aq. CuSO4 and sat.
aq. NaHCO3 solution, and dried (Na2SO4). Concentration followed by
silica gel column chromatography (EtOAc/hexane = 1/6) gave
silyloxy trityl ether as a mixture of diastereomers (16.8 g, 28.5 mmol,
84%). Anal. Found: C, 75.17; H, 8.82%. Calcd. for C37H52O4Si: C,
75.46; H, 8.90%. To a solution of trityl ether (16.8 g, 28.5 mmol) in
ether (830 mL) was added HCO2H (760 mL) at ꢀ5 ꢁC. The reaction
solution was stirred at ꢀ5 ꢁC for 15 min before additions of CHCl3 and
H2O. The organic solution was separated, washed with sat. aq.
NaHCO3 solution, and dried (Na2SO4). Concentration followed by
silica gel column chromatography (5%EtOAc/hexane) gave silyl ether
as a mixture of diastereomers (7.02 g, 20.3 mmol, 71%). Anal. Found:
C, 61.98; H, 10.72%. Calcd. for C18H38O4Si: C, 62.38; H, 11.05. A
reaction mixture of alcohol (7.02 g, 20.3 mmol), PCC (6.50 g,
30.2 mmol), and MS 4A (3 g) in CH2Cl2 (150 mL) was stirred at
room temperature for 16 h before addition of ether. The mixture was
filtered, and then the filtrate was concentrated. The residue was applied
to silica gel column chromatography (10% EtOAc/hexane) to give
unstable aldehyde as a mixture of diastereomers (6.14 g, 17.8 mmol,
88%). Anal. Found: C, 62.44; H, 10.26%. Calcd. for C18H36O4Si: C,
62.74; H, 10.53. To a suspension of ClPh3PCH2OCH3 (18.5 g,
54.0 mmol) in THF (300 mL) was added KHMDS (53.0 mL, 0.5 M in
toluene, 26.5 mmol) at ꢀ70 ꢁC. After the mixture was stirred at ꢀ70 ꢁC
for 30 min, aldehyde (6.14 g, 17.8 mmol) in THF (30 mL) was added.
The reaction mixture was stirred at ꢀ70 ꢁC for 30 min and then at room
temperature for 1 h. After addition of hexane, the mixture was filtered.
The filtrate was concentrated, and then the residue was applied to silica
gel column chromatography (1% EtOAc/hexane and EtOAc/
hexane = 1/8) to give isomeric mixture of enol ether (6.08 g,
16.3 mmol, 92%). Anal. Found: C, 64.37; H, 10.78%. Calcd. for
(1R,2S)-2-(2-Hydroxyeth-1-yl)cyclopentyl benzoate (23). A reac-
tion solution of trityl ether 22 (23.8 g, 49.9 mmol) and PPTS (17 mg,
0.068 mmol) in MeOH (150 mL) was heated under refluxing for 4 h
before addition of a few drops of Et3N. After concentration, the residue
was applied to silica gel column chromatography (EtOAc/hexane =
1/5) to give alcohol 23 (8.76 g, 37.4 mmol, 75%) as a colorless oil,
20
½ꢀꢃ
ꢀ48 (c 0.7, CHCl3). 1H-NMR (CDCl3) ꢂ: 1.28 (1H, m), 1.58
D
(1H, m), 1.68–1.87 (4H, m), 1.98–2.09 (2H, m), 2.23 (1H, m), 2.43
(1H, br. s), 3.71 (1H, ddd, J ¼ 11:0, 5.5, 5.5 Hz), 3.80 (1H, ddd,
J ¼ 11:0, 6.4, 6.4 Hz), 5.11 (1H, ddd, J ¼ 5:9, 3.5, 3.5 Hz), 7.41–7.45
(2H, m), 7.55 (1H, m), 7.98–8.03 (2H, m). 13C-NMR (CDCl3) ꢂ: 22.9,
30.7, 31.6, 36.6, 42.5, 61.5, 81.8, 128.3, 129.5, 130.5, 132.9, 166.8; IR
ꢃmax (CHCl3): 3500, 2950, 1709 cmꢀ1. Anal. Found: C, 71.80; H,
7.69%. Calcd. for C14H18O3: C, 71.77; H, 7.74%.
E-3-[(1S,2R)-2-(Triisopropylsilyloxy)cyclopent-1-yl]-3-propenal (25).
A reaction mixture of alcohol 23 (8.76 g, 37.4 mmol), PCC (9.67 g,
44.9 mmol), and MS 4A (0.60 g) in CH2Cl2 (100 mL) was stirred at
room temperature for 16 h before addition of ether. After the mixture
was filtered, the filtrate was concentrated, and then the residue was
applied to silica gel column chromatography (EtOAc/hexane = 1/9)
to give unstable aldehyde (6.59 g, 28.4 mmol, 76%) as a colorless oil,
20
½ꢀꢃ
ꢀ51 (c 2.2, CHCl3). 1H-NMR (CDCl3) ꢂ: 1.30 (1H, m), 1.74–
D
1.88 (3H, m), 2.06–2.16 (2H, m), 2.47 (1H, ddd, J ¼ 16:5, 8.9, 1.8 Hz),
2.58 (1H, m), 2.76 (1H, ddd, J ¼ 16:5, 5.1, 1.4 Hz), 5.04 (1H, m),
7.42–7.45 (2H, m), 7.55 (1H, m), 8.01–8.07 (2H, m), 9.79 (1H, dd,
J ¼ 1:8, 1.4 Hz). 13C-NMR (CDCl3) ꢂ: 22.5, 30.1, 31.3, 39.8, 47.4,
81.0, 128.2, 129.4, 130.2, 132.8, 166.3, 201.3. A reaction mixture
of unstable aldehyde (6.59 g, 28.4 mmol), TIPSOTf (8.40 mL,
31.2 mmol), DBU (9.30 mL, 62.2 mmol), and DMAP (3.10 g,
25.4 mmol) in CH2Cl2 (30 mL) was stirred at room temperature for
3 h before addition of sat. aq. NaHCO3 solution. The organic solution
was separated, washed with sat. aq. CuSO4 solution and sat. aq.
NaHCO3 solution, and dried (Na2SO4). Concentration followed by
silica gel column chromatography (1% EtOAc/hexane) gave unstable
isomeric mixture of silyl enol ether (11.0 g, 28.4 mmol, 100%). A
reaction mixture of silyl enol ether (11.0 g, 28.4 mmol), NMO (4.40 g,
37.6 mmol), and 2% aq. OsO4 solution in acetone (117 mL), tert-BuOH
(29 mL), and H2O (29 mL) was stirred at room temperature for 20 h
before addition of sat. aq. Na2S2O3 solution. After concentration of the
mixture, the residue was dissolved in EtOAc and H2O. The organic
solution was separated and dried (Na2SO4). Concentration followed by
silica gel column chromatography (EtOAc/hexane = 1/2) gave
polymer of ꢀ-hydroxy aldehyde (6.54 g). To an ice-cooled solution
of this polymer (6.54 g) in EtOH (20 mL) was added NaBH4 (1.00 g,
26.4 mmol). The resulting reaction mixture was stirred at room
temperature for 4 h before addition of 1 M aq. HCl solution. After
neutralization with sat. aq. NaHCO3 solution, the mixture was
concentrated. The residue was dissolved in EtOAc and H2O. The
EtOAc solution was separated, washed with brine, and dried (Na2SO4).
Concentration followed by silica gel column chromatography (EtOAc/
hexane = 1/2) gave a diastereomeric mixture of glycol (5.03 g,
C
20H40O4Si: C, 64.47; H, 10.82. A reaction solution of enol ether
(2.43 g, 6.52 mmol) and 50% CH3CO2H (140 mL) in THF (140 mL)
was stood at room temperature for 110 h before additions of sat. aq.
NaHCO3 and CHCl3. The organic solution was separated and dried
(Na2SO4). Concentration followed by silica gel column chromatog-
raphy (5% EtOAc in hexane) gave aldehyde 11 (1.93 g, 6.51 mmol,
20
99%) as a colorless oil, ½ꢀꢃ
þ53 (c 1.3, CHCl3). 1H-NMR (CDCl3)
D
ꢂ: 0.80–0.95 (3H, m), 1.04 (18H, s), 1.49 (1H, m), 1.63–1.75 (2H, m),
1.85 (1H, m), 1.92 (1H, m), 2.02 (1H, m), 2.73 (1H, m), 4.13 (1H, ddd,
J ¼ 5:9, 5.9, 5.9 Hz), 6.13 (1H, dd, J ¼ 15:6, 5.9 Hz), 6.79 (1H, dd,
J ¼ 15:6, 8.0 Hz), 9.50 (1H, d, J ¼ 8:0 Hz). 13C-NMR (CDCl3) ꢂ:
12.2, 18.0, 21.8, 29.0, 35.3, 52.3, 78.9, 132.4, 160.7, 194.0. IR ꢃmax
(CHCl3): 2962, 2944, 2867, 1685, 1367, 1238, 1215, 1126, 1012 cmꢀ1
.
HRFABMS m=z ðM þ HÞþ: calcd. for C17H33O2Si, 297.2250; found,
297.2252.

1712
S. YAMAUCHI et al.
20.1 mmol, 71%, 2 steps) as a colorless oil. Anal. Found: C, 66.91; H,
7.40%. Calcd. for C14H18O4: C, 67.18; H, 7.25%. A reaction solution
of glycol (5.03 g, 20.1 mmol) and trityl chloride (6.20 g, 22.2 mmol) in
pyridine (20 mL) was stirred at room temperature for 16 h before
additions of H2O and EtOAc. The organic solution was separated,
washed with sat. aq. CuSO4 solution, sat. aq. NaHCO3 solution, and
brine, and dried (Na2SO4). Concentration followed by silica gel
column chromatography (EtOAc/hexane = 1/9) gave a diastereomer-
ic mixture of hydroxy trityl ether (9.26 g, 18.8 mmol, 94%) as a
colorless oil. Anal. Found: C, 80.53; H, 6.65%. Calcd. for C33H32O4:
C, 80.46; H, 6.55%. To a solution of hydroxy trityl ether (9.26 g,
18.8 mmol) and iso-Pr2NEt (27.5 mL, 158 mmol) in CH2Cl2 (25 mL)
was added MOMCl (6.10 mL, 80.3 mmol). The reaction mixture was
stirred at room temperature for 16 h before additions of MeOH and
H2O. The organic solution was separated, washed with 1 M aq. HCl
solution and sat. aq. NaHCO3 solution, and dried. Concentration gave
crude benzoyloxy MOM ether. A reaction solution of crude benzoate
in 1 M aq. NaOH solution (166 mL) and EtOH (470 mL) was stirred at
60 ꢁC for 12 h before addition of CHCl3. The organic solution was
separated and dried (Na2SO4). Concentration gave crude alcohol. To
an ice-cooled solution of crude alcohol and 2,6-lutidine (4.00 mL,
34.2 mmol) in CH2Cl2 (25 mL) was added TIPSOTf (5.60 mL,
20.8 mmol). The resulting reaction solution was stirred at room
temperature for 2 h before addition of sat. aq. NaHCO3 solution. The
organic solution was separated, washed with sat. aq. CuCO4 solution
and sat. aq. NaHCO3 solution, and dried (Na2SO4). Concentration
followed by silica gel column chromatography (1% EtOAc/hexane)
gave diastereomeric mixture of silyl ether 24 (9.40 g, 16.0 mmol, 85%,
3 steps). This resulting silyl ether 24 was converted to (1S,2R)-
79.0, 129.8, 149.0, 200.7. HRFABMS m=z ðM þ HÞþ: calcd. for
20
C21H41O2Si 353.2876; found, 353.2877. Ketone 26: ½ꢀꢃ
ꢀ63 (c 1.0,
D
CHCl3).
Stereoselective reduction of ketone 14. To a solution of ketone 14
(0.11 g, 0.31 mmol) in toluene (4 mL) was added a solution of (R)-(þ)-
2-methyl-CBS-oxazaborolidine (0.36 g, 1.30 mmol) in toluene (1 mL)
and catecholborane (0.13 mL, 1.22 mmol) in toluene (3 mL) at ꢀ70 ꢁC.
After the reaction mixture was stirred at ꢀ70 ꢁC for 1 h, MeOH was
added, and then the mixture was filtered. The filtrate was concentrated.
The resulting residue was applied to silica gel column chromatography
(1% EtOAc in hexane) to give 3S-alcohol 13 (69 mg, 0.19 mmol, 61%).
Ketone 14 (33 mg, 0.094 mmol, 30%) was recovered. Alcohol 27 was
obtained from 26 by employing (S)-(ꢀ)-2-methyl-CBS-oxazaboroli-
dine.
Isomerization of 3R-alcohol 12 to 3S-alcohol 13. A reaction
solution of 3R-alcohol 12 (0.59 g, 1.66 mmol), Ph3P (0.88 g,
3.36 mmol), p-nitrobenzoic acid (0.56 g, 3.35 mmol), and DEAD
(1.53 mL, 40% in toluene, 3.36 mmol) in THF (5 mL) was stirred at
room temperature for 4 h before additions of H2O and EtOAc. The
organic solution was separated, washed with sat. aq. NaHCO3 solution
and brine, and dried (Na2SO4). Concentration followed by silica gel
column chromatography (hexane/toluene = 3/1) gave p-nitrobenzoate
(0.53 g). A reaction solution of p-nitrobenzoate (0.53 g) in 1 M aq.
NaOH solution (25 mL) and EtOH (100 mL) was stirred at room
temperature for 3 h before additions of CHCl3 and H2O. The organic
solution was separated and dried (Na2SO4). Concentration followed
by silica gel column chromatography (3% EtOAc in hexane) gave
3S-alcohol 13 (0.35 g, 0.99 mmol, 60%, 2 steps).
propenal 25 by the same method as that described for the synthesis of
20
(1R,2S)-propenal 11. ½ꢀꢃ
ꢀ54 (c 0.7, CHCl3).
D
(3S)-3-Benzyloxy1-[(1R,2S)-2-(triisopropylsilyloxy)cyclopent-1-yl]-
heptane (15). A reaction mixture of alcohol 13 (3.74 g, 10.5 mmol),
vacuum-dried MgO (0.58 g, 14.4 mmol), and 2-benzyloxymethylpy-
ridinium triflate (7.40 g, 21.1 mmol) in benzotrifluoride (22 mL) was
stirred at 85 ꢁC for 72 h before filtration with EtOAc. The filtrate was
concentrated, and then the residue was applied to silica gel column
chromatography (10% EtOAc/hexane) to give benzyl ether 15 (2.80 g,
(E,3S)-1-[(1R,2S)-2-(Triisopropylsilyloxy)cyclopent-1-yl]-1-hepten-
3-ol (13). To a solution of n-BuLi (15.2 mL, 2.60 M in hexane,
39.5 mmol) in THF (20 mL) was added a solution of aldehyde 11
(3.10 g, 10.5 mmol) in THF (10 mL) at ꢀ70 ꢁC. After the reaction
solution was stirred at ꢀ70 ꢁC for 1 h, sat. aq. NH4Cl solution and
EtOAc were added. The organic solution was separated, washed with
brine, and dried (Na2SO4). Concentration followed by silica gel
column chromatography (1% EtOAc in hexane) gave 3R-alcohol 12
(2.34 g, 6.60 mmol, 63%, Rf: 0.28) as a colorless oil and 3S-alcohol 13
6.30 mmol, 60%) as a colorless oil together with recovered alcohol 13
20
(1.43 g, 4.03 mmol, 38%). ½ꢀꢃ
þ11 (c 0.6, CHCl3). 1H-NMR
D
(CDCl3) ꢂ: 0.88 (3H, t, J ¼ 7:2 Hz), 1.00–1.20 (3H, m), 1.05 (18H, s),
1.27–1.34 (3H, m), 1.34–1.50 (3H, m), 1.55–1.70 (3H, m), 1.77 (1H,
m), 1.85 (1H, m), 1.95 (1H, m), 2.49 (1H, m), 3.66 (1H, m), 4.01 (1H,
m), 4.31 (1H, d, J ¼ 12:0 Hz), 4.55 (1H, d, J ¼ 12:0 Hz), 5.35 (1H, dd,
J ¼ 15:6, 8.2 Hz), 5.53 (1H, dd, J ¼ 15:6, 7.8 Hz), 7.26 (1H, m), 7.31–
7.37 (4H, m). 13C-NMR (CDCl3) ꢂ: 12.3, 14.0, 18.10, 18.12, 22.0,
22.7, 27.7, 30.0, 35.2, 35.6, 51.6, 69.7, 79.4, 80.3, 127.3, 127.7, 127.8,
128.3, 128.4, 130.4, 136.5, 139.1. IR ꢃmax(CHCl3) 2947, 2337, 1466,
1272, 1095 cmꢀ1. EIMS m=z (%) 444 (Mþ, 7), 309 (100). Anal. Found:
(1.02 g, 2.88 mmol, 27%, Rf: 0.20) as a colorless oil. 3R-alcohol 12:
20
½ꢀꢃ
þ40 (c 1.2, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.91 (3H, t,
D
J ¼ 7:1 Hz), 0.92–1.09 (3H, m), 1.05 (18H, s), 1.20–1.40 (5H, m), 1.47
(1H, m), 1.50–1.61 (3H, m), 1.76 (1H, m), 1.80–1.94 (2H, m), 2.43
(1H, m), 3.99 (1H, ddd, J ¼ 5:6, 5.6, 5.6 Hz), 4.03 (1H, ddd, J ¼ 6:5,
6.5, 6.5 Hz), 5.48 (1H, dd, J ¼ 15:5, 6.8 Hz), 5.58 (1H, dd, J ¼ 15:5,
7.4 Hz). 13C-NMR (CDCl3) ꢂ: 12.2, 14.0, 18.0, 18.1, 21.7, 22.6, 27.7,
29.5, 34.9, 36.9, 51.4, 73.1, 79.3, 132.7, 134.0. Anal. Found: C, 70.81;
H, 11.82%. Calcd. for C21H42O2Si: C, 71.12; H, 11.94%. 3S-alcohol
20
C, 75.62%; H, 10.68%. Calcd. for C28H48O2Si: C, 75.61%; H, 10.88%.
20
13: ½ꢀꢃ
þ35 (c 1.2, CHCl3); 1H-NMR (CDCl3) ꢂ: 0.90 (3H, t,
(3R)-1-[(1S,2R)]-15: ½ꢀꢃ
ꢀ11 (c 0.3, CHCl3).
D
D
J ¼ 7:1 Hz), 0.97–1.08 (21H, m), 1.21–1.39 (5H, m), 1.40–1.50 (2H,
m), 1.50–1.60 (2H, m), 1.74 (1H, m), 1.84 (1H, m), 1.89 (1H, m), 2.43
(1H, m), 3.98 (1H, ddd, J ¼ 5:5, 5.5, 5.5 Hz), 4.03 (1H, ddd, J ¼ 6:4,
6.4, 6.4 Hz), 5.45–5.61 (2H, m). 13C-NMR (CDCl3) ꢂ: 12.3, 14.0, 18.0,
18.1, 21.9, 22.7, 27.6, 29.7, 35.1, 37.0, 51.6, 73.2, 79.4, 132.8, 134.3.
IR ꢃmax(CHCl3) 3610, 2947, 1651, 1056 cmꢀ1. EIMS m=z (%) 354
(1R,2S,3S)-3-Benzyloxy-1-[(1R,2S)-2-(triisopropylsilyloxy)cyclopent-
1-yl]-1,2-heptanediol (16). To an ice-cooled suspension of AD-mix-ꢁ
(11.6 g) and methanesulfonamide (0.79 g, 8.31 mmol) in tert-BuOH
(30 mL) and H2O (40 mL) was added a solution of alkene 15 (3.67 g,
8.25 mmol) in tert-BuOH (10 mL). The resulting reaction mixture was
stirred at room temperature for 76 h before additions of sat. aq.
Na2S2O3 solution and EtOAc. The organic solution was separated,
washed with brine, and dried (Na2SO4). Concentration followed by
silica gel column chromatography (5% EtOAc in hexane) gave
(1R,2S)-glycol 16 (2.96 g, 6.18 mmol, Rf: 0.18, 75%) as a colorless oil
(Mþ, 6), 337 (100). Anal. Found: C, 70.77%; H, 11.92%. Calcd. for
20
C21H42O2Si: C, 71.12%; H, 11.94%. 27: ½ꢀꢃ
ꢀ33 (c 1.2, CHCl3).
D
E-1-[(1R,2S)-2-(Triisopropylsilyloxy)cyclopent-1-yl]-1-hepten-3-one
(14). A reaction mixture of 3R-alcohol 12 (0.12 g, 0.34 mmol), PCC
(88 mg, 0.41 mmol), and MS 4A (0.5 g) in CH2Cl2 (20 mL) was stirred
at room temperature for 12 h before addition of ether. After the mixture
was filtered, the filtrate was concentrated. The residue was applied to
and (1S,2R)-glycol isomer (0.69 g, 1.44 mmol, Rf: 0.34, 17%) as a
20
colorless oil. (1R,2S)-glycol 16: ½ꢀꢃ
þ48 (c 0.4, CHCl3). 1H-NMR
D
(CDCl3) ꢂ: 0.91 (3H, t, J ¼ 6:8 Hz), 0.98–1.10 (3H, m), 1.06 (18H, s),
1.26–1.40 (4H, m), 1.50–1.60 (4H, m), 1.60–1.78 (3H, m), 1.78–1.95
(2H, m), 2.58 (1H, d, J ¼ 7:0 Hz), 2.73 (1H, d, J ¼ 3:7 Hz), 3.45–3.53
(2H, m), 3.84 (1H, m), 4.22 (1H, m), 4.48 (1H, d, J ¼ 11:2 Hz), 4.62
(1H, d, J ¼ 11:2 Hz), 7.26–7.36 (5H, m). 13C-NMR (CDCl3) ꢂ: 12.5,
14.0, 18.1, 18.2, 21.8, 22.7, 23.0, 27.5, 30.1, 35.2, 51.7, 71.1, 72.1,
74.1, 76.0, 80.2, 127.9, 128.5, 138.0. IR ꢃmax(CHCl3) 3740, 2946,
silica gel column chromatography (5% EtOAc in hexane) to give
20
ketone 14 (0.11 g, 0.31 mmol, 91%) as a colorless oil. ½ꢀꢃ
þ64
D
(c 1.4, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.92 (3H, t, J ¼ 7:4 Hz), 1.00–
1.10 (3H, m), 1.04 (18H, s), 1.33 (2H, m), 1.47 (1H, m), 1.60 (2H, m),
1.60–1.70 (2H, m), 1.80 (1H, m), 1.83–2.00 (2H, m), 2.52 (2H, t,
J ¼ 7:4 Hz), 2.57 (1H, m), 4.08 (1H, ddd, J ¼ 5:9, 5.9, 5.9 Hz), 6.11
(1H, d, J ¼ 16:0 Hz), 6.75 (1H, dd, J ¼ 16:0, 8.4 Hz). 13C-NMR
(CDCl3) ꢂ: 12.2, 13.8, 18.0, 21.8, 22.4, 26.4, 29.1, 35.2, 39.9, 51.9,
2337, 1519, 1049 cmꢀ1. Anal. Found: C, 70.45%; H, 10.71%. Calcd.
20
for C28H50O4Si: C, 70.24%; H, 10.53%. (1S,2R)-glycol: ½ꢀꢃ
þ50
D

(ꢀ)- and (þ)-Boronolide
1713
(c 0.6, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.90 (3H, t, J ¼ 7:0 Hz), 1.00–
1.20 (3H, m), 1.09 (18H, s), 1.20–1.40 (4H, m), 1.45 (1H, m), 1.50–
1.65 (3H, m), 1.65–1.90 (3H, m), 1.91 (1H, m), 2.05 (1H, m), 2.59 (1H,
d, J ¼ 9:6 Hz), 3.31 (1H, m), 3.54 (1H, m), 3.76 (1H, m), 3.82 (1H, d,
J ¼ 9:1 Hz), 4.22 (1H, m), 4.61 (2H, s), 7.26–7.40 (5H, m). 13C-NMR
(CDCl3) ꢂ: 12.6, 14.1, 18.05, 18.14, 20.4, 23.0, 24.7, 27.3, 31.1, 34.3,
49.1, 73.1, 73.2, 73.7, 79.4, 80.3, 127.6, 127.9, 128.4, 138.8. EIMS m=z
(%) 477 (Mþ ꢀ 1, 4), 355 (100). Anal. Found: C, 70.42; H, 10.62%.
70%, 6.13 mmol) in CHCl3 (15 mL) and Na2HPO4–NaH2PO4 buffer
(pH 8, 15 mL) was stirred at room temperature for 16 h. After addition
of sat. aq. Na2S2O3 solution, the organic solution was separated,
washed with sat. aq. NaHCO3 solution, and dried (Na2SO4). Concen-
tration followed by silica gel column chromatography (EtOAc/
hexane = 1/2) gave lactone 20 (0.32 g, 0.76 mmol, 50%) as a colorless
20
oil. Ketone 19 (0.26 g, 0.64 mmol, 42%) was recovered. ½ꢀꢃ
þ9
D
(c 0.9, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.88 (3H, t, J ¼ 7:1 Hz), 1.22–
1.32 (3H, m), 1.39 (1H, m), 1.56–1.79 (5H, m), 1.85 (1H, m), 2.062
(3H, s), 2.064 (3H, s), 2.38 (1H, ddd, J ¼ 18:1, 9.3, 7.1 Hz), 2.50 (1H,
ddd, J ¼ 18:1, 6.0, 6.0 Hz), 3.47 (1H, m), 4.41 (1H, m), 4.56 (1H, d,
J ¼ 11:6 Hz), 4.61 (1H, d, J ¼ 11:6 Hz), 5.28 (1H, dd, J ¼ 5:6,
5.6 Hz), 5.39 (1H, dd, J ¼ 5:6, 4.5 Hz), 7.26–7.35 (5H, m). 13C-NMR
(CDCl3) ꢂ: 13.9, 18.1, 20.8, 20.9, 22.6, 22.9, 27.8, 29.5, 29.6, 70.6,
71.4, 72.4, 77.7, 78.3, 127.9, 128.0, 128.5, 137.9, 169.6, 170.3. IR
Calcd. for C28H50O4Si: C, 70.24; H, 10.53%. Glycol 28: AD-mix-ꢀ
20
was employed to give the desired compound in 81% yield, ½ꢀꢃ
(c 2.5, CHCl3).
ꢀ48
D
(1R,2R)-1-[(1S)-1-Benzyloxypent-1-yl]-2-[(1R,2S)-2-(triisopropyl-
silyloxy)cyclopent-1-yl]ethylene diacetate (17). A reaction solution of
glycol 16 (1.48 g, 3.09 mmol) and DMAP (0.20 g, 1.64 mmol) in
pyridine (15 mL) and Ac2O (15 mL) was stirred at room temperature
for 18 h before addition of ice. After 6 h at room temperature, EtOAc
was added. The organic solution was separated, washed with sat. aq.
NaHCO3 solution and brine, and dried (Na2SO4). Concentration
ꢃ
max(CHCl3) 2962, 2360, 1735, 1519, 1241, 1049. HRFABMS m=z
ðM þ HÞþ: calcd for C23H33O7, 421.2226; found, 421.2224.
20
(5S,6S,7S,8R)-20: ½ꢀꢃ
ꢀ9 (c 0.8, CHCl3).
D
followed by silica gel column chromatography (5% EtOAc in hexane)
20
(5R,6R,7R,8S)-6,7,8-Triacetoxy-5-dodecanolide (21). A reaction
mixture of benzyl ether (0.32 g, 0.76 mmol) and 20% Pd(OH)2/C
(0.3 g) in EtOAc (20 mL) was stirred under H2 gas at the ambient
temperature for 7 h before filtration. The filtrate was concentrated. A
reaction solution of the residue, Ac2O (0.93 mL, 9.84 mmol), pyridine
(1.59 mL, 19.7 mmol), and DMAP (1 mg, 0.0082 mmol) in CH2Cl2
(15 mL) was stirred at room temperature for 8 h before addition of
H2O. The organic solution was separated, washed with 1 M aq. HCl
solution and sat. aq. NaHCO3 solution, and dried (Na2SO4). Concen-
tration followed by silica gel column chromatography (EtOAc/
hexane = 1/1) gave triacetate (0.27 g, 0.73 mmol, 96%) as a colorless
gave diacetate 17 (1.59 g, 2.82 mmol, 91%) as a colorless oil; ½ꢀꢃ
D
þ22 (c 0.5, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.86 (3H, t, J ¼ 7:0 Hz),
0.92–1.12 (3H, m), 1.04 (18H, s), 1.20–1.32 (3H, m), 1.34 (1H, m),
1.54–1.70 (8H, m), 2.02 (3H, s), 2.03 (3H, s), 2.20 (1H, m), 3.45 (1H,
m), 3.98 (1H, m), 4.57 (1H, d, J ¼ 11:8 Hz), 4.65 (1H, d, J ¼ 11:8 Hz),
5.12 (1H, dd, J ¼ 7:7, 3.8 Hz), 5.61 (1H, dd, J ¼ 7:7, 1.4 Hz), 7.26–
7.35 (5H, m). 13C-NMR (CDCl3) ꢂ: 12.4, 14.0, 18.1, 18.2, 20.9, 21.0,
22.4, 22.6, 23.2, 27.8, 29.5, 35.5, 49.5, 71.6, 71.9, 74.2, 76.2, 77.7,
127.5, 127.8, 128.3, 138.2, 170.1, 170.4. IR ꢃmax (CHCl3) 2954, 2337,
1743, 1519, 1319, 1049 cmꢀ1. EIMS m=z (%) 563 (Mþ þ 1, 0.4), 173
(100). Anal. Found: C, 68.34; H, 9.74%. Calcd. for C32H54O6Si:
20
20
oil, ½ꢀꢃ
ꢀ25 (c 1.0, EtOH), ½ꢀꢃ
ꢀ20 (c 1.25, EtOH) in the
D
D
20
C, 68.28; H, 9.67%. Diaceate-29: ½ꢀꢃ
ꢀ22 (c 2.9, CHCl3).
literature. The NMR data agreed with those in the literature.13)
D
20
(5S,6S,7S,8R)-21: ½ꢀꢃ
þ25 (c 1.0, EtOH).
D
(1R,2R)-1-[(1S)-1-Benzyloxypent-1-yl]-2-[(1S,2S)-2-hydroxycyclo-
pent-1-yl]ethylene diacetate (18). To a solution of silyl ether 17
(0.52 g, 0.92 mmol) in THF (30 mL) was added HF-pyridine (4.90 mL,
70%, 189 mmol). The resulting reaction mixture was stirred at room
temperature for 22 h before additions of sat. aq. NaHCO3 and EtOAc.
The organic solution was separated, washed with sat. aq. Cu2SO4, sat.
aq. NaHCO3 solution, and brine, and dried (Na2SO4). Concentration
followed by silica gel column chromatography (EtOAc/hexane = 1/5)
(þ)-Boronolide (1). Lactone 21 was converted to (þ)-boronolide
20
(1) by the same method as that described in the literature,14) ½ꢀꢃ
D
20
þ23 (c 0.5, EtOH), ½ꢀꢃ
þ26 (c 0.7, EtOH) in the literature. The
D
NMR data agreed with those in the literature.5) ꢄ99%ee (Chiralpak
AD-H, 250 mm ꢅ 4:6 mm i.d., 5 mm, iso-PrOH/hexane = 5/95, 1 mL/
20
min, 210 nm, tR 18 min). (ꢀ)-Boronolide (2): ½ꢀꢃ
EtOH). ꢄ99%ee (tR 23 min).
ꢀ25 (c 0.1,
D
20
gave alcohol 18 (0.35 g, 0.86 mmol, 93%) as a colorless oil, ½ꢀꢃ
D
þ17 (c 1.0, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.88 (3H, t, J ¼ 7:0 Hz),
1.24–1.38 (4H, m), 1.43 (1H, m), 1.50–1.70 (6H, m), 1.80–1.94 (2H,
m), 2.06 (3H, s), 2.07 (3H, s), 2.52 (1H, s), 3.47 (1H, m), 3.70 (1H, m),
4.55 (1H, d, J ¼ 11:5 Hz), 4.62 (1H, d, J ¼ 11:5 Hz), 5.19 (1H, dd,
J ¼ 4:9, 4.9 Hz), 5.35 (1H, dd, J ¼ 4:9, 4.9 Hz), 7.27–7.30 (2H, m),
7.34–7.35 (3H, m). 13C-NMR (CDCl3) ꢂ: 14.0, 20.8, 21.0, 21.2, 22.7,
24.2, 27.4, 29.4, 33.2, 48.8, 72.0, 72.1, 73.9, 74.5, 77.3, 127.8, 128.0,
128.4, 138.0, 170.9, 171.3. IR ꢃmax(CHCl3) 3730, 2954, 2337, 1735,
1519, 1241, 1049 cmꢀ1. EIMS m=z (%) 407 (Mþ þ 1, 10), 180 (100).
Evaluation of the plant growth-inhibitory activity. The plant
growth-inhibitory activities of (þ)- and (ꢀ)-boronolides were eval-
uated by using lettuce (Lactuca sativa L.: green-wave (Takii Seed Co.,
Kyoto, Japan)) and Italian ryegrass (Lolium multiflorum Lam.: wase-
fudo (Takii Seed Co., Kyoto, Japan)). A sheet of filter paper (90 mm or
40 mm in diameter) was placed in a 90 mm or 40 mm Petri dish and
wetted with 500 mL or 160 mL of the test sample solution dissolved in
acetone at a concentration of 6.0 mM. After drying the filter paper,
3 mL or 1 mL of water was poured into the dish to adjust the
concentration to 1.0 mM. Thirty seeds of each plant were then placed
on the filter paper, and after the Petri dishes were sealed with Parafilm,
they were incubated in the dark at 20 ꢁC. After 3 and 5 d for lettuce and
barnyard grass, respectively, the lengths of their roots and shoots were
measured with a ruler. The respective root and shoot lengths of the
control were ca. 3 cm and 1 cm for lettuce, and 4 cm and 3 cm for
grass. The experiments were performed in triplicate or more for each
sample (n ¼ 3).
Anal. Found: C, 67.96%; H, 8.46%. Calcd. for C23H34O6: C, 67.96%;
20
H, 8.43%. (1S,2S)-1-[(1R)]-2-[(1R,2R)]-18: ½ꢀꢃ
ꢀ17 (c 2.4, CHCl3).
D
(1R,2R)-[(1S)-1-Benzyloxypent-1-yl]-2-[(1R)-2-oxocyclopent-1-yl]-
ethylene diacetate (19). A reaction mixture of alcohol 18 (0.73 g,
1.80 mmol), PCC (0.42 g, 1.95 mmol), and MS 4A (1 g) in CH2Cl2
(50 mL) was stirred at room temperature for 16 h before addition of
ether and filtration. The filtrate was concentrated, and then the residue
was applied to silica gel column chromatography (EtOAc/hex-
ane = 1/3) to give ketone 19 (0.62 g, 1.53 mmol, 85%) as a colorless
20
oil, ½ꢀꢃ
þ52 (c 0.5, CHCl3). 1H-NMR (CDCl3) ꢂ: 0.88 (3H, t,
D
Acknowledgments
J ¼ 7:0 Hz), 1.22–1.40 (4H, m), 1.49–1.80 (4H, m), 1.80–2.05 (3H,
m), 1.96 (3H, s), 2.05 (3H, s), 2.17–2.32 (2H, m), 3.42 (1H, m), 4.56
(1H, d, J ¼ 11:7 Hz), 4.63 (1H, d, J ¼ 11:7 Hz), 5.19 (1H, dd, J ¼ 7:5,
4.0 Hz), 5.70 (1H, dd, J ¼ 7:5, 3.0 Hz), 7.27–7.35 (5H, m). 13C-NMR
(CDCl3) ꢂ: 14.0, 20.6, 20.7, 20.9, 22.6, 24.1, 27.8, 29.2, 37.9, 49.7,
69.5, 71.8, 73.3, 127.8, 128.2, 128.5, 137.9, 169.3, 170.4, 216.2. IR
Part of this study was performed at INCS (Johoku
station) of Ehime University. We are grateful to
Marutomo Co. for financial support.
ꢃ
max(CHCl3) 3031, 2962, 2870, 1743, 1241 cmꢀ1. HRFABMS m=z
References and Notes
ðM þ HÞþ: calcd. for C23H33O6, 405.2277; found, 405.2273. (1S,2S)-
20
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D
(5R,6R,7R,8S)-8-Benzyloxy-6,7-diacetoxy-5-dodecanolide (20). A
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