Synthesis of marine oxylipin agardhilactone and its analogues: A structural revision

Article abstract of DOI:10.3987/COM-08-S(F)97

Synthesis of four analogues of the marine oxylipin agardhilactone was carried out. The relative configuration of agardhilactone was determined by comparison with agardhilactone acetate and four analogues. Furthermore, synthesis of agardhilactone was achie

Full text of DOI:10.3987/COM-08-S(F)97

HETEROCYCLES, Vol. 77, No. 2, 2009
1185
HETEROCYCLES, Vol. 77, No. 2, 2009, pp. 1185 - 1208. © The Japan Institute of Heterocyclic Chemistry
Received, 5th August, 2008, Accepted, 26th September, 2008, Published online, 29th September, 2008
DOI: 10.3987/COM-08-S(F)97
SYNTHESIS OF MARINE OXYLIPIN AGARDHILACTONE AND ITS
ANALOGUES: A STRUCTURAL REVISION
Hiroaki Miyaoka,* Yoshinori Hara, Ikuo Shinohara, Takao Kurokawa,
Etsuko Kawashima, and Yasuji Yamada
School of Pharmacy, Tokyo University of Pharmacy and Life Sciences,
1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan;
E-mail: miyaokah@ps.toyaku.ac.jp
Abstract – Synthesis of four analogues of the marine oxylipin agardhilactone was
carried out. The relative configuration of agardhilactone was determined by
comparison with agardhilactone acetate and four analogues. Furthermore,
synthesis of agardhilactone was achieved. The absolute configuration of
agardhilactone was successfully determined by this synthesis.
INTRODUCTION
Marine organisms, and especially marine algae, are an extremely rich source of novel oxylipins. Many of
the oxylipins are of interest given their unique structures, peculiar biosynthetic pathways and biological
activities.1 Agardhilactone is a structurally unique oxylipin which was first isolated from the marine red
alga Agardhiella subulata, obtained off Massachusetts, by Gerwick et al in 1996.2 Agardhilactone is a
novel tricyclic oxylipin containing δ-lactone, cyclopentane and epoxide rings and a conjugated diene
moiety. The structure was determined based on the NMR analysis of agardhilactone acetate and GC-MS
analysis of the (-)-menthoxycarbonyl derivative. However, the complete structure of agardhilactone was
not determined since agardhilactone is a particle constituent. The relative configuration of the
cyclopentane ring system (C-6, C-8, C-9 and C-10) was determined to be 6S*, 8R*, 9S* and 10R*,
1
respectively, based on the NOESY analysis combined with H-1H coupling constants of agardhilactone
acetate. However, the relative configuration at C-5 remains unknown. The absolute configuration of the
secondary hydroxy group at C-18 was determined as being in the S configuration by converting
agardhilactone to the known (-)-menthoxycarbonyl derivative. Although the biological activity of
agardhilactone has not been reported, it is anticipated that agardhilactone possesses biological activity
This paper is dedicated to Professor Emeritus Keiichiro Fukumoto on the occasion of his 75th birthday.

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HETEROCYCLES, Vol. 77, No. 2, 2009
since oxylipins generally possess a broad range of biological activities including inhibitory activity
against phospholipase A2.1
Many syntheses of carbocyclic oxylipins have been performed given their unique structural features and
potential biological significance.1 The authors previously synthesized the carbocyclic oxylipins
constanolactone3 and bacillariolide,4 and recently reported the total synthesis and structural revision of
agardhilactone.5 In this paper, the authors wish to report the detailed synthesis and structural revision of
agardhilactone.
As mentioned above, given that the relative configuration at C-5 of agardhilactone had not been
determined, the authors began by synthesizing analogues 1 - 4 of agardhilactone in an effort to determine
the relative configuration at C-5 and to confirm the relative configurations at C-6, C-8, C-9 and C-10.
Analogues 1 - 4 correspond to four diastereomers of 16,17-dihydro-18-dehydroxyagardhilactone.
O
O
O
O
H
H
H
5
5
6
8
8
10
O
O
OR
9
9
H
18
agardhilactone : R = H
agardhilactone acetate : R = Ac
1 : 5R*, 8R*, 9S*
2 : 5R*, 8S*, 9R*
3 : 5S*, 8R*, 9S*
4 : 5S*, 8S*, 9R*
(Gerwick's structures)
Figure 1. Proposed structure of agardhilactone and analogues 1 - 4.
RESULTS AND DISCUSSION
Analogues 1 - 4 were respectively synthesized from (±)-4-vinyldihydrofuran-2-one (5)6 via ring-closing
metathesis (RCM) and allylic halide-alkyne coupling reactions. Lactone 5 was treated with LDA in THF
at -78 °C and then with 3-iodopropene to give trans-lactone 6 as a single compound (Scheme 1). The
relative configuration of trans-lactone 6 was determined by its NOESY. The trans-configuration of the
allyl and vinyl groups was indicated by the NOE correlation between H-6 and H-9 and between H-7 and
H-10, as shown in Figure 2. Lactone 6 was reduced to the
hemiacetal with DIBALH, and the hemiacetal was then treated
with Grignard reagent (TBDMSOCH2CH2CH2CH2MgI)7 in
DME at 0 °C to afford a mixture of α-alcohol 7a and β-alcohol
7b (7a/7b = 3:1), which were readily separated by silica gel
chromatography. In this reaction, when Et2O was used as the
solvent, α-alcohol 7a was predominantly obtained (7a/7b = 5:1).
9
6
10
7
NOE
6
Figure 2. Selected NOE correlations of 6.

HETEROCYCLES, Vol. 77, No. 2, 2009
1187
The relative configuration of the hydroxy group at C-5 was
determined by the NOESY of tetrahydrofuran 8 derived
from α-alcohol 7a. α-Alcohol 7a was treated with TsCl and
DABCO in AcOEt at 0 °C to give tetrahydrofuran 8. The
NOE correlation between H-5 and H-10 in tetrahydrofuran
8 indicated that C-5 and C-10 adopt a cis-configuration, as
5
10
NOE
8
Figure 3. Selected NOE correlations of 8.
shown in Figure 3. Therefore, the configuration of the hydroxy group at C-5 of 7a was determined as
being in the α-configuration, and that of the hydroxy group at C-5 of 7b, which is a diastereomer of 7a, to
be in the β-configuration.
OH
OTBDMS
O
O
OTBDMS
H
H
H
H
7
9
H
O
b, c
5
a
d
5
6
O
7a
O
10
10
OH
H
H
7a : 5α-OH
7b : 5β-OH
5
8
6
Scheme 1. Reagents and conditions: (a) LDA, 3-iodopropene, THF, -78 °C to rt, 74%; (b) DIBALH, CH2Cl2,
-78 °C, 98%; (c) TBDMSOCH2CH2CH2CH2MgI, DME, 0 °C, 73% (7a), 25% (7b); (d) TsCl, DABCO, AcOEt,
0 °C, 71%.
The RCM reaction of α-alcohol 7a with 1st generation Grubbs’ catalyst8 in CH2Cl2 afforded the
cyclopentene derivative in 99% yield (Scheme 2). The primary hydroxy group of the cyclopentene
derivative was protected as the pivalate, while the secondary hydroxy group was protected as the TBDMS
ether to give cyclopentene 9. Epoxidation of cyclopentene 9 with m-CPBA in the presence of Na2HPO4 in
CH2Cl2 afforded a mixture of α-epoxide 10a and β-epoxide 10b (10a/10b = 1:3). The diastereomeric
mixture was separated by silica gel chromatography. The relative configuration of epoxides 10a and 10b
was determined by NOESY. The epoxide of 10a was determined to be in the α-configuration from the
NOE correlation between H-9 and H-11, while the epoxide of 10b was determined to be in the
β-configuration from the NOE correlation between H-9 and H-10. α-Epoxide 10a was converted to
allylic iodide 11 in four steps consisting of (1) reductive removal of the pivaloyl group with DIBALH, (2)
oxidation of the hydroxy group with Dess-Martin periodinane9 to give the aldehyde, followed by a Wittig
reaction with Ph3P=CHCO2Me, (3) reduction of the α,β-unsaturated ester with DIBALH, and finally (4)
tosylation of the hydroxy group with Ts2O and pyridine, followed by treatment with NaI. The coupling
reaction of allylic iodide 11 with hept-1-yne was achieved by treatment with CuI, NaI and K2CO3 to give
enyne 12.10 The two TBDMS groups of enyne 12 were removed by treatment with tetrabutylammonium
fluoride (TBAF) in DMF at 40 °C to give the diol. The diol was treated with tetrapropylammonium
perruthenate (TPAP) and 4-methylmorpholine N-oxide (NMO) to directly give the δ-lactone.11 Finally,

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HETEROCYCLES, Vol. 77, No. 2, 2009
alkyne hydrogenation with 5% Pd on BaSO4 in the presence of quinoline12 afforded analogue 1, whose
relative configuration is 5R*, 6S*, 8R*, 9S* and 10R*. Analogue 2, whose relative configuration is 5R*,
6S*, 8S*, 9R* and 10R*, was synthesized from β-epoxide 10b in a similar manner as described above.
TBDMSO
H
TBDMSO
H
TBDMSO
H
OTBDMS
OTBDMS
OTBDMS
d
H
H
+
a - c
8
7a
8
10
9
9
OPiv
OPiv
10b
11
OPiv
O
O
H
H
H
9
H
H
H
NOE
H
10a
O
TBDMSO
H
OTBDMS
j - l
TBDMSO
H
OTBDMS
O
H
e - h
i
5
6
8
10a
I
O
10
O
H
O
O
9
H
H
11
1
12
O
H
m - t
5
10b
6
8
10
O
9
H
2
Scheme 2. Reagents and conditions: (a) Grubbs’ catalyst 1st generation, CH2Cl2, rt, 99%; (b) PivCl, pyridine,
CH2ClCH2Cl, 0 °C to rt, 82%; (c) TBDMSCl, imidazole, DMF, 45 °C, 99%; (d) m-CPBA, Na2HPO4, CH2Cl2, 0 °C
to rt, 23% (10a), 77% (10b); (e) DIBALH, CH2Cl2, -78 °C, 87%; (f) Dess-Martin periodinane, NaHCO3, CH2Cl2, rt,
then Ph3P=CHCO2Me, reflux, 61%; (g) DIBALH, CH2Cl2, -78 °C, 79%; (h) Ts2O, pyridine, CH2Cl2, rt, then NaI,
acetone, rt, 72%; (i) hept-1-yne, CuI, NaI, K2CO3, DMF, rt, 63%; (j) TBAF, DMF, 40 °C, 73%; (k) TPAP, NMO,
MS 4A, CH2ClCH2Cl, rt, 60%; (l) H2, 5% Pd on BaSO4, quinoline, MeOH, rt, 79%; (m) DIBALH, CH2Cl2, -78 °C,
90%; (n) Dess-Martin periodinane, NaHCO3, CH2Cl2, rt, then Ph3P=CHCO2Me, reflux, 86%; (o) DIBALH, CH2Cl2,
-78 °C, 77%; (p) Ts2O, pyridine, CH2Cl2, rt, then NaI, acetone, rt, 64%; (q) hept-1-yne, CuI, NaI, K2CO3, DMF, rt,
79%; (r) TBAF, DMF, 40 °C, 69%; (s) TPAP, NMO, MS 4A, CH2ClCH2Cl, rt, 70%; (t) H2, 5% Pd on BaSO4,
quinoline, MeOH, rt, 71%.
Analogues 3 and 4 were synthesized from β-alcohol 7b (Scheme 3). The RCM reaction of β-alcohol 7b
with 1st generation Grubbs’ catalyst in CH2Cl2 afforded the cyclopentene derivative. The primary
hydroxy group of the cyclopentene derivative was protected as the pivalate to give cyclopentene 13.
Protection of the secondary hydroxy group in 13 as the TBDMS ether gave cyclopentene 14.
Diastereoselective epoxidation of cyclopentene 14 with m-CPBA was carried out and predominantly
afforded β-epoxide 15b (α-epoxide 15a/15b = 1:15). Cyclopentene 14 reacted with m-CPBA at the less
hindered side and principally gave β-epoxide 15b. The mixture of the two diastereomers was separated by
silica gel chromatography and the relative configuration of epoxides 15a and 15b was determined by

HETEROCYCLES, Vol. 77, No. 2, 2009
1189
NOESY. The epoxide of 15a was determined to be in the α-configuration from the NOE correlation
between H-9 and H-11, and the epoxide of 15b was determined to be in the β-configuration from the
NOE correlation between H-9 and H-10. α-Epoxide 15a was obtained stereoselectively by the
epoxidation of β-alcohol 13 followed by protection of the secondary hydroxy group. β-Alcohol 13 was
13
treated with TBHP in the presence of VO(acac)2 to give the α-epoxide as the sole product. The
stereochemical outcome of this epoxidation may be accounted for by invoking a process involving
coordination of the hydroxy group at C-5 to the reagent. The hydroxy group in the α-epoxide was
protected as the TBDMS ether to afford α-epoxide 15a. α-Epoxide 15a was converted to analogue 3,
whose relative configuration is 5S*, 6S*, 8R*, 9S* and 10R*, according to the aforementioned established
method. β-Epoxide 15b was also converted to analogue 4, whose relative configuration is 5S*, 6S*, 8S*,
9R* and 10R*, according to the aforementioned established method.
TBDMSO
H
TBDMSO
H
OR
OTBDMS
d
OTBDMS
OTBDMS
H
a, b
H
H
8
7b
+
8
10
9
OPiv
9
OPiv
OPiv
15b
11
O
O
H
H
H
O
NOE
H
H
H
13 : R = H
14 : R = TBDMS
H
15a
c
O
O
H
O
H
e, f
o - v
g - n
5
5
15b
13
15a
6
6
8
8
10
10
O
O
9
9
H
H
3
4
Scheme 3. Reagents and conditions: (a) Grubbs’ catalyst 1st generation, CH2Cl2, rt, 82%; (b) PivCl, pyridine,
CH2ClCH2Cl, 0 °C to rt, 86%; (c) TBDMSCl, imidazole, DMF, 45 °C, 94%; (d) m-CPBA, Na2HPO4, CH2Cl2, 0 °C
to rt, 6% (15a), 91% (15b); (e) TBHP, VO(acac)2, CH2Cl2, rt, 83%; (f) TBDMSOTf, 2,6-lutidine, CH2Cl2, -78 °C,
88%; (g) DIBALH, CH2Cl2, -78 °C, 84%; (h) Dess-Martin periodinane, NaHCO3, CH2Cl2, rt, then
Ph3P=CHCO2Me, reflux, 83%; (i) DIBALH, CH2Cl2, -78 °C, 90%; (j) Ts2O, pyridine, CH2Cl2, rt, then NaI, acetone,
rt, 73%; (k) hept-1-yne, CuI, NaI, K2CO3, DMF, rt, 84%; (l) TBAF, DMF, 40 °C, 40%; (m) TPAP, NMO, MS 4A,
CH2ClCH2Cl, rt, 64%; (n) H2, 5% Pd on BaSO4, quinoline, MeOH, rt, 88%; (o) DIBALH, CH2Cl2, -78 °C, 96%;
(p) Dess-Martin periodinane, NaHCO3, CH2Cl2, rt, then Ph3P=CHCO2Me, reflux, 78%; (q) DIBALH, CH2Cl2,
-78 °C, 94%; (r) Ts2O, pyridine, CH2Cl2, rt, then NaI, acetone, rt, 62%; (s) hept-1-yne, CuI, NaI, K2CO3, DMF, rt,
60%; (t) TBAF, DMF, 40 °C, 69%; (u) TPAP, NMO, MS 4A, CH2ClCH2Cl, rt, 40%; (v) H2, 5% Pd on BaSO4,
quinoline, MeOH, rt, 80%.
The NMR spectra of synthesized analogues 1 - 4 were compared with that of agardhilactone acetate.2 The
1
13
characteristic H- and C-NMR data are shown in Table 1. When the NMR of the four analogues 1 - 4
was compared, the chemical shift and coupling constant of 4 were remarkably similar to that of
agardhilactone acetate2. Therefore, the relative configuration of agardhilactone was estimated to be 5S*,

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HETEROCYCLES, Vol. 77, No. 2, 2009
6S*, 8S*, 9R* and 10R*. On the basis of this result, the authors examined the synthesis of natural
agardhilactone.
Table 1. Selected NMR data of agardhilactone acetate and analogues 1 - 4.
agardhilactone acetate
1 (5R *, 8R *, 9S *)
(J in Hz)
2 (5R *, 8S *, 9R *)
(J in Hz)
1H
13C
1H
13C 1H
No.
13C
No.
(J in Hz)
No.
5 4.24 ddd, 11.7, 2.4, 2.4 78.5 5 4.18 ddd, 11.1, 9.5, 2.6 83.6 5 4.30 ddd, 9.8, 3.5, 3.5
81.1
55.8
61.3
42.7
8 3.46 br d, 7.5
55.7 8 3.52 d, 2.2
60.2 9 3.37 d, 2.6
44.7 10 3.18 d, 7.8
57.5 8 3.45 d, 2.6
61.1 9 3.37 dd, 2.5, 1.7
43.3 10 2.63 m
9 3.40 dd, 2.7, 1.4
10 2.71 br dd, 9.0, 9.0
3 (5S *, 8R *, 9S *)
(J in Hz)
4 (5S *, 8S *, 9R *)
(J in Hz)
1H
13C
1H
No.
13C
No.
5 4.13 ddd, 10.5, 10.4, 3.0 83.6 5 4.23 ddd, 11.7, 2.6, 2.6 78.5
8 3.56 br s
9 3.32 d, 2.5
10 2.66 d, 8.2
58.5 8 3.45 br s
55.6
60.2
44.7
61.1 9 3.39 dd, 2.5, 1.2
44.6 10 2.70 dd, 9.0, 8.9
The authors designed the synthesis of natural agardhilactone via the separation route of the two
diastereomers, which were obtained by a coupling reaction of a racemic synthetic intermediate of
analogue 4 with a chiral side-chain segment. The chiral side-chain segment 19 (C14-C20) was
synthesized from (S)-3-hydroxypent-1-yne (16)14(Scheme 4). The hydroxy group in 16 was protected as
the TBDPS ether and subsequently treated with catecholborane15 and then iodine16 to give E-iodoalkene
17 as the sole product. The coupling reaction of E-iodoalkene 17 with (trimethylsilyl)acetylene was
achieved by treatment with (Ph3P)4Pd, CuI and PrNH2 in benzene to give enyne 18.17 Removal of the
TMS and TBDPS groups in enyne 18 was carried out by treatment with TBAF to give the alcohol. The
hydroxy group was then acetylated to afford acetate 19, [α]D24 -104.1˚ (c 0.63, CHCl3), which is the chiral
side-chain segment (C14-C20).
OTBDPS
OAc
OH
OTBDPS
20
e, f
a - c
d
I
14
TMS
16
17
18
19
Scheme 4. Reagents and conditions: (a) TBDPSCl, imidazole, DMF, rt, 83%; (b) catecholborane, 80 °C; (c) I2,
NaOH aq., Et2O, 0 °C, 75% (two steps); (d) (trimethylsilyl)acetylene, (Ph3P)4Pd, CuI, PrNH2, benzene, rt, 63%; (e)
TBAF, THF, rt, 90%; (f) AcCl, DMAP, CH2Cl2, 0 °C, 86%.
The coupling reaction of enyne 19 and allylic iodide 20, a racemic synthetic intermediate of analogue 4,
was achieved by treatment with CuI, NaI and K2CO3 and gave a diastereomeric mixture of dienynes 21
and 22 (Scheme 5). Without separation of the mixture, the two TBDMS groups in dienynes 21 and 22
were removed by treatment with TBAF in DMF at 60 °C to give the corresponding diols. The diols were

HETEROCYCLES, Vol. 77, No. 2, 2009
1191
treated with TPAP and NMO to directly give the δ-lactones. Partial hydrogenation of the alkynes with 5%
Pd on BaSO4 in the presence of quinoline afforded a diastereomeric mixture of E,Z,E-trienes 23 and 24.
Separation of the diastereomeric mixture using a chiral HPLC column gave acetates 23, [α]D20 -179.6˚ (c
0.52, CHCl3), and 24, [α]D24 +165.2˚ (c 0.50, CHCl3). The spectral data of acetate 23 was identical to that
of agardhilactone acetate.2 The absolute configuration of acetate 23 was determined by application of a
modified Mosher’s method.18 Agardhilactone acetate (23) was treated with K2CO3 in MeOH to give diol
25. Diol 25 was converted to (S)-α-methoxy-α-(trifluoromethyl)phenylacetyl (MTPA) ester (S)-26 and
(R)-MTPA ester (R)-26. The absolute configuration at C-5 was determined to be in the S configuration by
1
comparison of the H-NMR of the (S)- and (R)-MTPA esters. Therefore, the absolute configurations of
agardhilactone and agardhilactone acetate (23) were determined to be 5S, 6S, 8S, 9R, 10R and 18S.
Saponification of acetate 23 followed by lactonization of the resulting dihydroxycarboxylic acid gave
31
lactone 27, [α]D -104.4˚ (c 0.09, CHCl3). The spectral data of 27 were identical to that of
agardhilactone.2
OTBDMS
OTBDMS
OTBDMS
TBDMSO
H
TBDMSO
H
TBDMSO
H
OAc
OAc
a
+
I
O
O
O
H
H
H
21
22
20
O
O
O
O
H
H
H
b - d
5
+
6
8
10
O
OR
O
OAc
9
H
18
24
23 : R = Ac
27 agardhilactone : R = H
j, k
e
OH
H
OMTPA
H
H
CO2Me
CO2Me
f, g
or
h, i
O
OH
O
H
25
26
Scheme 5. Reagents and conditions: (a) 19, CuI, NaI, K2CO3, DMF, rt, 90% (21 and 22); (b) TBAF, DMF, 60 °C,
56%; (c) TPAP, NMO, MS 4A, CH2ClCH2Cl, rt, 67%; (d) H2, 5% Pd on BaSO4, quinoline, MeOH, rt, then
separation by HPLC, 19% (23), 17% (24); (e) K2CO3, MeOH, rt, 60%; (f) (S)-MTPACl, DMAP, CH2ClCH2Cl, rt;
(g) H2, 10% Pd on C, MeOH, rt, 25% (two steps); (h) (R)-MTPACl, DMAP, CH2ClCH2Cl, rt; (i) H2, 10% Pd on C,
MeOH, rt, 64% (two steps); (j) NaOH aq., THF, rt; (k) DCC, DMAP, CH2Cl2, rt, 90% (two steps).

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HETEROCYCLES, Vol. 77, No. 2, 2009
In conclusion, the total synthesis of agardhilactone has been achieved in 17 steps from lactone 5. The
absolute configuration of agardhilactone was successfully determined by this total synthesis. The
synthesis is flexible and potentially allows for introduction of a variety of unnatural substitutions. The
preparation of such analogues and evaluation of the bioactivity of agardhilactone is currently underway.
EXPERIMENTAL
Optical rotations were measured using a Jasco P-1030 polarimeter or a Jasco DIP-360 polarimeter. IR
spectra were recorded using a Jasco FT-IR/620 spectrometer. UV spectra were recorded using a Jasco
1
V-550 spectrophotometer. H- and 13C-NMR spectra were recorded on a Varian Mercury-300
spectrometer, a Bruker DRX-400 spectrometer or a Bruker DRX-500 spectrometer. Chemical shifts are
given on the δ (ppm) scale using TMS as the internal standard (s, singlet; d, doublet; t, triplet; m,
multiplet; br, broad). EIMS spectra were obtained using a Thermo Quest TSQ 700 spectrometer. High
resolution EIMS (HREIMS) spectra were obtained using a VG Auto Spec E spectrometer. ESIMS and
high resolution ESIMS (HRESIMS) spectra were obtained using a Micromass LCT spectrometer.
Elemental analysis data were obtained using an Elemental Vavio EL. Flash column chromatography was
performed using Kanto Chemical Silica Gel 60N (spherical, neutral) 40-50 μm.
(3S*,4S*)-3-Allyl-4-vinyldihydrofuran-2-one (6). A solution of BuLi (1.58 M in hexane, 8.10 mL, 12.8
mmol) was added to a cold (0 °C) solution of diisopropylamine (1.90 mL, 13.9 mmol) in THF (26.0 mL)
under an argon atmosphere. The mixture was stirred for 30 min at 0 °C and cooled to -78 °C. A solution
of 4-vinyldihydrofuran-2-one (5)5 (1.20 g, 10.7 mmol) in THF (1.00 mL) was added to the mixture and
stirred for 30 min at -78 °C. 3-Iodopropene (1.50 mL, 16.1 mmol) was added to this mixture at -78 °C.
The reaction mixture was warmed to rt for 5 h and diluted with Et2O, washed with saturated aqueous
NH4Cl, water and saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (hexane : acetone = 8 : 1) to give
1
trans-lactone 6 (1.20 g, 74% yield) as a colorless oil: IR (neat) cm-1: 2907, 1780; H-NMR (500 MHz,
CDCl3) δ : 5.78 (1H, m), 5.69 (1H, ddd, J = 17.8, 10.0, 8.2 Hz), 5.19 (2H, m), 5.11 (2H, m), 4.35 (1H, dd,
J = 8.7, 8.4 Hz), 3.90 (1H, dd, J = 9.5, 9.4 Hz), 2.98 (1H, m), 2.46 (3H, m); 13C-NMR (125 MHz, CDCl3)
δ : 177.6, 135.1, 133.8, 118.7, 118.4, 70.0, 44.9, 44.6, 32.1; EIMS m/z: 152 (M+, 28), 54 (100); Anal.
Calcd for C9H12O2: C, 71.03; H, 7.95. Found: C, 70.78; H, 7.99.
(2S*,3S*,4S*)-3-Allyl-8-tert-butyldimethylsiloxy-4-vinyloctane-1,4-diol (7a) and (2S*,3S*,4R*)-3-
Allyl-8-tert-butyldimethylsiloxy-4-vinyloctane-1,4-diol (7b). To a cold (-78 °C) solution of lactone 6
(1.87 g, 12.3 mmol) in CH2Cl2 (41.0 mL), was added DIBALH (0.90 M in hexane, 17.8 mL, 14.8 mmol)
under an argon atmosphere. The mixture was stirred for 20 min at -78 °C, added MeOH, diluted with

HETEROCYCLES, Vol. 77, No. 2, 2009
1193
Et2O and added saturated aqueous NaCl. The mixture was stirred for 3 h, dried over MgSO4 and
concentrated under reduced pressure. The residue was purified by silica gel column chromatography
(hexane : AcOEt = 4 : 1) to give anomeric mixture (1 : 1) of hemiacetal (1.85 g, 98% yield) as a colorless
oil: IR (neat) cm-1: 3416, 2934, 1642; 1H-NMR (400 MHz, CDCl3) δ : 5.81 (1.5H, m), 5.61 (0.5H, ddd, J
= 17.0, 9.7, 9.1 Hz), 5.40 (0.5H, m), 5.14 (0.5H, m), 5.06 (4H, m), 4.12 (0.5H, t, J = 8.5 Hz), 3.99 (0.5H, t,
J = 8.0 Hz), 3.81 (0.5H, t, J = 9.0 Hz), 3.59 (0.5H, t, J = 8.7 Hz), 3.05 (0.5H, br s), 2.88 (0.5H, br s), 2.76
13
(0.5H, m), 2.53 (0.5H, m), 2.23 (2H, m), 1.93 (1H, m); C-NMR (100 MHz, CDCl3) δ : 137.7, 137.6,
136.8, 135.9, 117.4, 116.7, 116.6, 115.8, 103.2, 98.6, 71.9, 71.3, 52.2, 49.8, 49.7, 46.8, 35.4, 31.2; EIMS
m/z: 136 (M+-H2O, 10), 83 (100); HREIMS m/z: 136.0918 (Calcd for C9H12O: M+-H2O, 136.0888).
To a solution of the above hemiacetal (33.0 mg, 214 μmol) in DME (1.10 mL), was added
4-tert-butyldimethylsiloxybutyl magnesium iodide6 (642 μL, 642 μmol) at 0 °C, followed by stirring for
30 min. The reaction mixture was diluted with Et2O, washed with saturated aqueous NH4Cl, water and
saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (hexane : Et2O = 1 : 2) to give α-alcohol 7a (53.5 mg, 73%
yield) and β-alcohol 7b (18.5 mg, 25% yield) as each colorless oil. 7a: IR (neat) cm-1: 3349, 2928;
1H-NMR (400 MHz, CDCl3) δ : 5.86 (1H, m), 5.79 (1H, m), 5.20 (1H, s), 5.17 (1H, m), 5.05 (2H, m),
3.60 (5H, m), 2.59 (1H, m), 2.20 (1H, m), 1.88 (2H, br s), 1.77 (2H, m). 1.54 (5H, m), 1.37 (1H, m), 0.88
(9H, s), 0.04 (6H, s); 13C-NMR (100 MHz, CDCl3) δ : 138.7, 137.7, 118.0, 116.4, 73.4, 64.0, 63.1, 46.8,
44.4, 35.1, 32.7, 32.5, 26.0, 22.5, 18.4, -5.3; EIMS m/z: 343 (M++H, 100); HREIMS m/z: 343.2649
1
(Calcd for C19H39O3Si: M++H, 343.2668). 7b: IR (neat) cm-1: 3290, 2857; H-NMR (400 MHz, CDCl3)
δ : 5.83 (2H, m), 5.10 (4H, m), 3.70 (5H, m), 2.42 (1H, m), 2.22 (1H, m), 1.72-1.20 (7H, m), 0.89 (9H, s),
13
0.05 (6H, s); C-NMR (100 MHz, CDCl3) δ : 139.0, 138.2, 117.1, 116.1, 71.6, 63.1, 63.0, 46.6, 45.2,
34.3, 32.5, 31.2, 26.0, 22.8, 18.4, -5.3; ESIMS m/z: 365 (M++Na, 100); HRESIMS m/z: 365.2472 (Calcd
for C19H38O3NaSi: M++Na, 365.2488).
4-[(2R*,3S*,4S*)-3-Allyl-4-vinyltetrahydrofuran-2-yl]butoxy-tert-butyldimethylsilane (8). To
a
solution of α-alcohol 7a (16.6 mg, 48.5 μmol) in AcOEt (1.00 mL) were added DABCO (11.1 mg, 58.2
μmol) and TsCl (8.1 mg, 72.8 μmol) at 0 °C, followed by stirring for 20 h. The reaction mixture was
diluted with Et2O, washed with saturated aqueous NaHCO3, water and saturated aqueous NaCl, dried over
MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column
chromatography (hexane : AcOEt = 5 : 1) to give tetrahydrofuran 8 (11.0 mg, 71% yield) as a colorless
oil: IR (neat) cm-1: 2929; 1H-NMR (400 MHz, CDCl3) δ : 5.71 (2H, m), 5.06 (1H, m), 5.00 (3H, m), 3.89
(1H, dd, J = 8.3, 8.0 Hz), 3.57 (4H, m), 2.55 (1H, m), 2.22 (1H, m), 2.15 (1H, m), 1.64-1.36 (7H, m), 0.89
(9H, s), 0.04 (6H, s); 13C-NMR (100 MHz, CDCl3) δ : 138.8, 136.2, 116.5, 115.9, 84.2, 71.5, 63.1, 50.5,

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HETEROCYCLES, Vol. 77, No. 2, 2009
50.1, 35.5, 34.7, 32.9, 25.9, 22.6, 18.4, -5.3; ESIMS m/z: 347 (M++Na, 100); HRESIMS m/z: 347.2408
(Calcd for C19H36O2NaSi: M++Na, 347.2382).
(1S*,5S*)-5-[(1R*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]cyclopent-2-enylmethyl
2,2-dimethyl-
propionate (9). To a solution of α-alcohol 7a (55.0 mg, 160 μmol) in CH2Cl2 (16.0 mL), was added
(benzylidene)bis(tricyclohexylphosphine)ruthenium(IV) dichloride7 (13.0 mg, 15.9 μmol) and stirred at rt
for 3 h. The reaction mixture was diluted with Et2O, filtered through silica gel and concentrated under
reduced pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt = 3 : 1)
1
to give cyclopentene (50.1 mg, 99% yield) as a colorless oil: IR (neat) cm-1: 3302, 2929; H-NMR (400
MHz, CDCl3) δ : 5.71 (1H, m), 5.46 (1H, m), 3.84 (1H, dd, J = 10.0, 3.7 Hz), 3.79 (2H, br s), 3.64 (2H,
m), 3.49 (1H, m), 3.32 (1H, dd, J = 10.0, 9.9 Hz), 2.85 (1H, m), 2.50 (1H, m), 2.05 (2H, m), 1.57 (4H,
13
m),1.43 (2H, m), 0.89 (9H, s), 0.05 (6H, s); C-NMR (100 MHz, CDCl3) δ : 130.8, 130.7, 75.4, 67.1,
63.2, 53.5, 50.9, 36.9, 35.5, 32.5, 25.9, 21.7, 18.4, -5.3; EIMS m/z: 315 (M++H, 100); HREIMS m/z:
315.2345 (Calcd for C17H35O3Si: M++H, 315.2355).
To a cold (0 °C) solution of the above cyclopentene (989 mg, 3.14 mmol) in CH2ClCH2Cl (32.0 mL),
were added pyridine (380 μL, 4.71 mmol) and pivaloyl chloride (454 μL, 3.77 mmol) and stirred at rt for
14 h. The reaction mixture was diluted with Et2O, washed with saturated aqueous NaHCO3, water and
saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (hexane : AcOEt = 6 : 1) to give alcohol (1.02 g, 82%
yield) as a colorless oil: IR (neat) cm-1: 3481, 2930, 1730; 1H-NMR (400 MHz, CDCl3) δ : 5.73 (1H, m),
5.59 (1H, m), 4.17 (1H, dd, J = 10.6, 5.7 Hz), 3.96 (1H, dd, J = 10.6, 6.6 Hz), 3.62 (2H, t, J = 6.0 Hz),
3.53 (1H, br s), 2.97 (1H, m), 2.49 (1H, m), 2.07 (2H, m), 1.84 (1H, d, J = 4.4 Hz), 1.60-1.48 (4H, m),
13
1.41 (2H, m), 1.20 (9H, s), 0.89 (9H, s), 0.05 (6H, s); C-NMR (100 MHz, CDCl3) δ : 178.6, 131.2,
130.9, 75.6, 67.9, 63.1, 48.2, 46.6, 38.8, 36.0, 35.1, 32.7, 27.2, 25.9, 22.1, 18.4, -5.3; ESIMS m/z: 421
(M++Na, 100); HRESIMS m/z: 421.2719 (Calcd for C22H42O4NaSi: M++Na, 421.2750).
To a solution of the above alcohol (510 mg, 1.28 mmol) in DMF (1.30 mL), were added imidazole (172
mg, 2.56 mmol) and TBDMSCl (289 mg, 1.92 mmol) and stirred at 45 °C for 12 h. The reaction mixture
was diluted with Et2O, washed with saturated aqueous NaHCO3, water and saturated aqueous NaCl, dried
over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column
chromatography (hexane : AcOEt = 10 : 1) to give TBDMS ether 9 (647 mg, 99% yield) as a colorless
oil: IR (neat) cm-1: 2955, 1732; 1H-NMR (400 MHz, CDCl3) δ : 5.70 (1H, m), 5.55 (1H, m), 4.12 (1H, dd,
J = 10.5, 5.4 Hz), 3.88 (1H, dd, J = 10.5, 7.0 Hz), 3.64 (1H, m), 3.60 (2H, t, J = 6.4 Hz), 2.83 (1H, m),
2.42 (1H, m), 2.18 (2H, m), 1.53-1.31 (6H, m), 1.19 (9H, s), 0.89 (9H, s), 0.86 (9H, s), 0.04 (12H, m);
13C-NMR (100 MHz, CDCl3) δ : 178.5, 131.5, 130.7, 75.4, 67.8, 63.2, 47.9, 44.9, 38.8, 34.9, 33.8, 33.2,
27.2, 26.0, 21.3, 18.3, 18.1, -4.2, -4.5, -5.3; ESIMS m/z: 535 (M++Na, 100); HRESIMS m/z: 535.3602

HETEROCYCLES, Vol. 77, No. 2, 2009
1195
(Calcd for C28H56O4NaSi2: M++Na, 535.3615).
(1S*,2S*,3S*,5R*)-3-[(1R*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-yl-
methyl 2,2-dimethylpropionate (10a) and (1R*,2S*,3S*,5S*)-3-[(1R*)-1,5-bis(tert-butyldimethyl-
siloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-ylmethyl 2,2-dimethylpropionate (10b). To a cold (0 °C)
solution of cyclopentene 9 (607 mg, 1.18 mmol) in CH2Cl2 (12.0 mL), were added Na2HPO4 (670 mg,
4.72 mmol) and 65% m-CPBA (467 mg, 1.77 mmol). After stirring for 5 h at rt, saturated aqueous
Na2S2O3 was added and stirred for 30 min. The mixture was diluted with Et2O, washed with saturated
aqueous NaHCO3, water and saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (CHCl3 : acetone = 100 : 1) to
give α-epoxide 10a (160 mg, 23% yield) and β-epoxide 10b (542 mg, 77% yield) as each colorless oil.
1
10a: IR (neat) cm-1: 2929, 1734; H-NMR (400 MHz, CDCl3) δ : 4.11 (1H, dd, J = 11.0, 4.6 Hz), 3.92
(1H, dd, J = 11.0, 7.6 Hz), 3.59 (2H, m), 3.54 (1H, ddd, J = 9.3, 3.8, 3.5 Hz), 3.46 (1H, m), 3.38 (1H, d, J
= 2.5 Hz), 2.57 (1H, m), 1.96 (1H, m), 1.89 (1H, m), 1.74 (1H, dd, J = 14.4, 2.1 Hz), 1.51-1.24 (6H, m),
1.20 (9H, s), 0.89 (9H, s), 0.87 (9H, s), 0.05 (12H, m); 13C-NMR (125 MHz, CDCl3) δ : 178.4, 75.5, 65.5,
63.1, 60.6, 58.8, 45.4, 42.0, 38.8, 34.3, 33.4, 29.5, 27.2, 26.0, 19.3, 18.3, 18.1, -4.0, -4.6, -5.3; ESIMS
m/z: 551 (M++Na, 100); HRESIMS m/z: 551.3602 (Calcd for C28H56O5NaSi2: M++Na, 551.3564). 10b: IR
(neat) cm-1: 2929, 1732; 1H-NMR (400 MHz, CDCl3) δ : 4.35 (1H, dd, J = 10.6, 4.3 Hz), 4.01 (1H, t, J =
10.3 Hz), 3.59 (3H, m), 3.50 (1H, m), 3.48 (1H, m), 2.16 (1H, m), 2.11 (1H, dd, J = 13.8, 7.6 Hz), 1.62
(1H, m), 1.55-1.38 (5H, m), 1.34 (2H, m), 1.22 (9H, s), 0.89 (9H, s), 0.87 (9H, s), 0.04 (12H, m);
13C-NMR (125 MHz, CDCl3) δ : 178.1, 74.6, 64.9, 63.1, 58.8, 57.0, 42.4, 40.3, 38.7, 34.7, 33.2, 31.2,
27.2, 26.0, 20.6, 18.3, 18.1, -4.2, -4.6, -5.3; ESIMS m/z: 551 (M++Na, 100); HRESIMS m/z: 551.3544
(Calcd for C28H56O5NaSi2: M++Na, 551.3564).
(1S*,2S*,3S*,5R*)-3-[(1R*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-2-[(1E)-3-iodopropenyl]-6-oxa-
bicyclo[3.1.0]hexane (11). To a cold (-78 °C) solution of α-epoxide 10a (966 mg, 1.82 mmol) in CH2Cl2
(18.0 mL), was added DIBALH (0.93 M in hexane, 2.93 mL, 2.73 mmol) under an argon atmosphere.
The mixture was stirred for 30 min at -78 °C, added MeOH, diluted with Et2O and added saturated
aqueous NaCl. The mixture was stirred for 3 h, dried over MgSO4 and concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt = 3 : 1) to give
1
alcohol (701 mg, 87% yield) as a colorless oil: IR (neat) cm-1: 3453, 2929; H-NMR (400 MHz, CDCl3)
δ : 3.59 (4H, m), 3.52 (1H, ddd, J = 9.9, 3.5, 3.4 Hz), 3.47 (1H, m), 3.41 (1H, d, J = 2.5 Hz), 2.39 (1H, dt,
J = 2.9, 6.9 Hz), 2.05 (1H, m), 1.91 (1H, ddd, J = 14.8, 10.4, 1.9 Hz), 1.72 (2H, m), 1.53-1.37 (5H, m),
1.27 (1H, m), 0.89 (18H, s), 0.05 (12H, m); 13C-NMR (100 MHz, CDCl3) δ : 75.8, 64.0, 63.2, 61.0, 59.0,
46.0, 45.7, 34.2, 33.4, 29.7, 26.0, 19.1, 18.3, 18.1, -4.1, -4.4, -5.3; ESIMS m/z: 467 (M++Na, 100);
HRESIMS m/z: 467.3011 (Calcd for C23H48O4NaSi2: M++Na, 467.2989).

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HETEROCYCLES, Vol. 77, No. 2, 2009
To a solution of the above alcohol (685 mg, 1.54 mmol) in CH2Cl2 (15.0 mL), were added NaHCO3 (1.29
g, 15.4 mmol) and Dess-Martin periodinane8 (1.96 g, 4.62 mmol), stirred for 1 h at rt and added excess
Na2S2O3. After stirring for 10 min, methyl (triphenylphosphoranylidene)acetate (2.57 g, 7.70 mmol) was
added and stirred under reflux for 14 h. The reaction mixture was diluted with Et2O and filtered through
silica gel and concentrated under reduced pressure. The residue was purified by silica gel column
chromatography (hexane : AcOEt = 6 : 1) to give α,β-unsaturated ester (468 mg, 61% yield) as a
colorless oil: IR (neat) cm-1: 2929, 1730; 1H-NMR (400 MHz, CDCl3) δ : 6.86 (1H, dd, J = 15.9, 8.0 Hz),
5.86 (1H, dd, J = 15.9, 1.2 Hz), 3.74 (3H, s), 3.60 (3H, m), 3.51 (1H, br s), 3.38 (1H, d, J = 2.5 Hz), 3.11
(1H, d, J = 8.0 Hz), 2.01 (1H, m), 1.88 (1H, ddd, J = 14.9, 9.4, 1.3 Hz), 1.79 (1H, dd, J = 14.9, 2.0 Hz),
13
1.52-1.18 (6H, m), 0.89 (9H, s), 0.88 (9H, s), 0.05 (12H, m); C-NMR (100 MHz, CDCl3) δ : 166.9,
148.5, 121.0, 75.0, 63.1, 60.5, 58.2, 51.6, 47.7, 43.8, 34.3, 33.4, 28.7, 26.0, 19.1, 18.3, 18.1, -4.0, -4.4,
-5.3; ESIMS m/z: 521 (M++Na, 100); HRESIMS m/z: 521.3119 (Calcd for C26H50O5NaSi2: M++Na,
521.3095).
To a cold (-78 °C) solution of α,β-unsaturated ester (468 mg, 934 μmol) in CH2Cl2 (9.40 mL), was added
DIBALH (0.93 M in hexane, 2.12 mL, 1.96 mmol) under an argon atmosphere. The mixture was stirred
for 20 min at –78 °C, added MeOH, diluted with Et2O and added saturated aqueous NaCl. The mixture
was stirred for 3 h, dried over MgSO4 and concentrated under reduced pressure. The residue was purified
by silica gel column chromatography (hexane : AcOEt = 3 : 1) to give allylic alcohol (351 mg, 79% yield)
as a colorless oil: IR (neat) cm-1: 3389, 2929; 1H-NMR (400 MHz, CDCl3) δ : 5.71 (1H, ddt, J = 15.7, 0.5,
5.2 Hz), 5.60 (1H, dd, J = 15.7, 7.7 Hz), 4.12 (2H, br s), 3.59 (3H, m), 3.48 (1H, br s), 3.33 (1H, d, J = 2.5
Hz), 2.96 (1H, d, J = 7.5 Hz), 1.95 (1H, m), 1.86 (1H, ddd, J = 14.7, 9.4, 1.4 Hz), 1.76 (1H, dd, J = 14.7,
13
2.0 Hz), 1.52-1.19 (7H, m), 0.89 (9H, s), 0.88 (9H, s), 0.06 (12H, m); C-NMR (100 MHz, CDCl3) δ :
132.5, 129.5, 75.1, 63.6, 63.2, 61.4, 58.2, 48.3, 43.7, 33.4, 28.8, 26.0, 18.3, 18.1, -4.0, -4.4, -5.3; ESIMS
m/z: 493 (M++Na, 100); HRESIMS m/z: 493.3173 (Calcd for C25H50O4NaSi2: M++Na, 493.3145).
To a solution of the above allylic alcohol (160 mg, 340 μmol) in CH2Cl2 (17.0 mL), were added pyridine
(550 μL, 6.80 mmol) and p-toluenesulfonic anhydride (444 mg, 1.36 mmol). After stirring at rt for 10 min,
acetone (11.0 mL) and NaI (1.50 g, 10.2 mmol) were added and stirred for 30 min. The reaction mixture
was diluted with Et2O and filtered through celite and concentrated under reduced pressure. The residue
was purified by silica gel column chromatography (hexane : AcOEt = 10 : 1) to give allylic iodide 11
1
(142 mg, 72% yield) as a colorless oil: IR (neat) cm-1: 2929; H-NMR (400 MHz, CDCl3) δ : 5.78 (1H,
ddt, J = 15.3, 0.7, 7.8 Hz), 5.60 (1H, dd, J = 15.3, 8.0 Hz), 3.86 (2H, d, J = 7.9 Hz), 3.58 (3H, m), 3.48
(1H, br s), 3.32 (1H, d, J = 2.5 Hz), 2.92 (1H, d, J = 7.9 Hz), 1.84 (3H, m), 1.52-1.21 (6H, m), 0.89 (9H,
s), 0.88 (9H, s), 0.05 (12H, m); 13C-NMR (100 MHz, CDCl3) δ : 134.4, 128.5, 75.1, 63.2, 61.0, 58.2, 48.2,
43.6, 34.3, 33.4, 28.8, 26.0, 19.4, 18.3, 18.1, 5.8, -3.9, -4.4, -5.3; ESIMS m/z: 603 (M++Na, 100);

HETEROCYCLES, Vol. 77, No. 2, 2009
1197
HRESIMS m/z: 603.2156 (Calcd for C25H49IO3NaSi2: M++Na, 603.2163).
(1S*,2S*,3S*,5R*)-3-[(1R*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-2-[(1E)-dec-1-en-4-ynyl]-6-oxa-
bicyclo[3.1.0]hexane (12). To a solution of K2CO3 (230 mg, 1.66 mmol), NaI (249 mg, 1.66 mmol) and
CuI (158 mg, 831 μmol) in DMF (2.80 mL), were added hept-1-yne (109 μL, 831 μmol) and allylic
iodide 11 (161 mg, 277 μmol). After stirring at rt for 3 h, the reaction mixture was diluted with Et2O,
washed with saturated aqueous NH4Cl, water and saturated aqueous NaCl, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by silica gel column chromatography
(hexane : Et2O = 20 : 1) to give eneyne 12 (95.8 mg, 63% yield) as a colorless oil: IR (neat) cm-1: 2930;
1H-NMR (400 MHz, CDCl3) δ : 5.59 (1H, ddt, J = 15.4, 7.8, 1.4 Hz), 5.48 (1H, ddt, J = 15.4, 0.5, 5.0 Hz),
3.59 (3H, m), 3.47 (1H, br s), 3.33 (1H, d, J = 2.5 Hz), 2.91 (3H, m), 2.18 (2H, m), 1.95 (1H, m), 1.85
(1H, ddd, J = 14.7, 9.5, 1.3 Hz), 1.75 (1H, dd, J = 14.6, 1.8 Hz), 1.56-1.21 (12H, m), 0.89 (21H, m), 0.06
13
(12H, m); C-NMR (100 MHz, CDCl3) δ : 131.3, 125.6, 82.7, 75.2, 63.3, 61.6, 58.3, 48.4, 43.9, 34.4,
33.5, 31.1, 28.8, 28.7, 26.0, 22.2, 22.1, 19.5, 18.8, 18.3, 18.1, 14.0, -3.9, -4.4, -5.3; ESIMS m/z: 571
(M++Na, 100); HRESIMS m/z: 571.4033 (Calcd for C32H60O3NaSi2: M++Na, 571.3979).
(6R*)-6-{(1S*,2S*,3S*,5R*)-2-[(1E,4Z)-Deca-1,4-dienyl]-6-oxabicyclo[3.1.0]hex-3-yl}tetrahydro-
pyran-2-one (1). To a solution of enyne 12 (95.0 mg, 173 μmol) in DMF (1.70 mL), was added TBAF
(1.0 M in THF, 865 μL, 865 μmol). After stirring at 40 °C for 12 h, the reaction mixture was diluted with
AcOEt, washed with saturated aqueous NH4Cl, water and saturated aqueous NaCl, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by silica gel column chromatography
(hexane : acetone = 2 : 1) to give diol (40.7 mg, 73% yield) as a colorless oil: IR (neat) cm-1: 3387, 2930;
1H-NMR (400 MHz, CDCl3) δ : 5.62 (1H, m), 5.55 (1H, dt, J = 15.4, 4.7 Hz), 3.64 (2H, t, J = 6.5 Hz),
3.59 (1H, m), 3.46 (1H, m), 3.39 (1H, d, J = 2.6 Hz), 3.08 (1H, d, J = 7.4 Hz), 2.92 (2H, m), 2.18 (4H, m),
1.99 (1H, m), 1.61-1.27 (14H, m), 0.89 (3H, t, J = 7.1 Hz); 13C-NMR (100 MHz, CDCl3) δ : 130.2, 126.6,
83.0, 76.6, 73.9, 62.8, 62.3, 59.2, 47.9, 42.1, 36.3, 32.7, 32.6, 31.1, 28.7, 22.2, 22.0, 18.7, 14.0; ESIMS
m/z: 343 (M++Na, 100); HRESIMS m/z: 343.2261 (Calcd for C20H32O3Na: M++Na, 343.2249).
To a solution of the above diol (10.0 mg, 31.2 μmol) in CH2ClCH2Cl (1.70 mL), were added MS 4A
(15.5 mg), NMO (18.2 mg, 156 μmol) and TPAP (0.54 mg, 1.6 μmol). After stirring at rt for 12 h, the
reaction mixture was diluted with Et2O, filtered through silica gel and concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt = 3 : 2) to give
1
lactone (5.9 mg, 60% yield) as a colorless oil: IR (neat) cm-1: 2927, 1733; H-NMR (400 MHz, CDCl3)
δ : 5.60 (2H, m), 4.19 (1H, m), 3.54 (1H, d, J = 2.2 Hz), 3.40 (1H, d, J = 2.5 Hz), 3.23 (1H, d, J = 5.4 Hz),
2.90 (2H, d, J = 2.3 Hz), 2.55 (1H, ddd, J = 17.3, 7.0, 6.7 Hz), 2.41 (1H, ddd, J = 17.3, 7.7, 7.3 Hz), 2.17
13
(2H, m), 2.05-1.77 (6H, m), 1.50 (1H, m), 1.40-1.26 (5H, m), 0.90 (3H, t, J = 7.0 Hz); C-NMR (100
MHz, CDCl3) δ : 172.0, 129.6, 126.9, 83.5, 82.9, 76.6, 60.9, 57.7, 47.9, 43.0, 31.1, 29.4, 28.7, 28.3, 26.3,

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22.2, 22.0, 18.7, 18.1, 14.0; ESIMS m/z: 339 (M++Na, 100); HRESIMS m/z: 339.1918 (Calcd for
C20H28O3Na: M++Na, 339.1936).
A solution of the above lactone (14.0 mg, 44.2 μmol) in MeOH (1.40 mL) in the presence of 5% Pd on
BaSO4 (6.6 mg) and quinoline (8.8 μL) was stirred at rt for 2 h under a hydrogen atmosphere. The
reaction mixture was diluted with Et2O and filtered through silica gel and the filtrate was concentrated
under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3 : AcOEt =
1
9 : 1) to give analogue 1 (11.1 mg, 79% yield) as a colorless oil: IR (neat) cm-1: 2926, 1737; H-NMR
(400 MHz, CDCl3) δ : 5.57 (1H, m), 5.43 (1H, m), 5.33 (2H, m), 4.18 (1H, m), 3.52 (1H, d, J = 2.2 Hz),
3.37 (1H, d, J = 2.6 Hz), 3.18 (1H, d, J = 7.8 Hz), 2.74 (2H, t, J = 6.7 Hz), 2.55 (1H, dt, J = 17.3, 6.9 Hz),
2.41 (1H, dt, J = 17.3, 7.6 Hz), 2.06-1.78 (8H, m), 1.39-1.22 (7H, m), 0.89 (3H, t, J = 6.8 Hz); 13C-NMR
(100 MHz, CDCl3) δ : 172.0, 131.2, 130.5, 128.7, 126.7, 83.6, 61.1, 57.7, 48.1, 43.3, 31.5, 30.4, 29.4,
29.3, 28.3, 27.1, 26.3, 22.5, 18.1, 14.0; ESIMS m/z: 341 (M++Na, 100); HRESIMS m/z: 341.2088 (Calcd
for C20H30O3Na: M++Na, 341.2093).
(6R*)-6-{(1R*,2S*,3S*,5S*)-2-[(1E,4Z)-Deca-1,4-dienyl]-6-oxabicyclo[3.1.0]hex-3-yl}tetrahydro-
pyran-2-one (2). Analogue 2 was synthesized from β-epoxide 10b according to the above synthetic
1
method of analogue 1 from α-epoxide 10a. 2: a colorless oil; IR (neat) cm-1: 2925, 1738; H-NMR (400
MHz, CDCl3) δ : 5.58 (2H, m), 5.39 (2H, m), 4.30 (1H, m), 3.45 (1H, d, J = 2.6 Hz), 3.37 (1H, m), 2.78
(2H, t, J = 6.3 Hz), 2.63 (1H, m), 2.57 (1H, m), 2.42 (1H, m), 2.14 (1H, m), 2.02 (2H, m), 1.91-1.66 (6H,
13
m), 1.36-1.25 (6H, m), 0.88 (3H, t, J = 6.7 Hz); C-NMR (100 MHz, CDCl3) δ : 171.7, 131.1, 131.0,
130.1, 126.8, 81.1, 61.3, 55.8, 44.0, 42.7, 31.5, 30.6, 30.5, 29.5, 29.3, 27.1, 26.2, 22.5, 18.8, 14.0; ESIMS
m/z: 341 (M++Na, 78), 195 (100); HRESIMS m/z: 341.2110 (Calcd for C20H30O3Na: M++Na, 341.2093).
(1S*,5S*)-5-[(1S*)-5-tert-Butyldimethylsiloxy-1-hydroxypentyl]cyclopent-2-enylmethyl 2,2-di-
methylpropionate (13). To a solution of β-alcohol 7b (54.5 mg, 159 μmol) in CH2Cl2 (16.0 mL), was
added (benzylidene)bis(tricyclohexylphosphine)ruthenium(IV) dichloride (13.0 mg, 15.9 μmol) and
stirred at rt for 3 h. The reaction mixture was diluted with Et2O, filtered through silica gel and
concentrated under reduced pressure. The residue was purified by silica gel column chromatography
(hexane : AcOEt = 3 : 1) to give cyclopentene (41.0 mg, 82% yield) as a colorless oil: IR (neat) cm-1:
1
3348, 2929; H-NMR (400 MHz, CDCl3) δ : 5.76 (1H, m), 5.54 (1H, m), 3.68 (2H, m), 3.65 (2H, m),
3.47 (1H, dd, J = 10.2, 7.2 Hz), 2.85 (1H, m), 2.48 (1H, m), 2.23 (2H, m), 1.60-1.36 (6H, m), 0.89 (9H, s),
0.04 (6H, s); 13C-NMR (100 MHz, CDCl3) δ : 131.8, 130.5, 73.2, 66.4, 63.2, 50.3, 47.5, 34.4, 33.6, 32.6,
25.9, 22.7, 18.4, -5.3; EIMS m/z: 315 (M++H, 8), 147 (100); HREIMS m/z: 314.2258 (Calcd for
C17H34O3Si: M+, 314.2277).
To a cold (0 °C) solution of the above cyclopentene (252 mg, 801 μmol) in CH2ClCH2Cl (8.00 mL), were

HETEROCYCLES, Vol. 77, No. 2, 2009
1199
added pyridine (129 μL, 1.60 mmol) and pivaloyl chloride (148 μL, 1.20 mmol) and stirred at rt for 12 h.
The reaction mixture was diluted with Et2O, washed with saturated aqueous NaHCO3, water and saturated
aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane : AcOEt = 6 : 1) to give alcohol 13 (276 mg, 86% yield) as a
1
colorless oil: IR (neat) cm-1: 3484, 2931, 1731; H-NMR (400 MHz, CDCl3) δ : 5.76 (1H, m), 5.58 (1H,
m), 4.07 (1H, dd, J = 10.7, 6.4 Hz), 3.96 (1H, dd, J = 10.7, 6.3 Hz), 3.62 (3H, m), 2.91 (1H, m), 2.40 (2H,
m), 2.08 (1H, m), 1.59-1.35 (7H, m), 1.19 (9H, s), 0.89 (9H, s), 0.04 (6H, s); 13C-NMR (100 MHz,
CDCl3) δ : 178.5, 131.8, 130.3 73.5, 67.4, 63.1, 47.9, 46.2, 38.8, 35.1, 32.9, 32.7, 27.2, 25.9, 22.5, 18.3,
-5.3; ESIMS m/z: 421 (M++Na, 100); HRESIMS m/z: 421.2761 (Calcd for C22H42O4NaSi: M++Na,
421.2750).
(1S*,5S*)-5-[(1S*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]cyclopent-2-enylmethyl 2,2-dimethyl-
propionate (14). To a solution of alcohol 13 (243 mg, 609 μmol) in DMF (600 μL), were added
imidazole (83.0 mg, 1.21 mmol) and TBDMSCl (138 mg, 914 μmol) and stirred at 45 °C for 17 h. The
reaction mixture was diluted with Et2O, washed with saturated aqueous NaHCO3, water and saturated
aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane : AcOEt = 10 : 1) to give TBDMS ether 14 (295 mg, 94%
1
yield) as a colorless oil: IR (neat) cm-1: 2930, 1732; H-NMR (400 MHz, CDCl3) δ : 5.71 (1H, m), 5.52
(1H, m), 4.09 (1H, dd, J = 10.6, 6.0 Hz), 3.94 (1H, dd, J = 10.6, 6.4 Hz), 3.72 (1H, m), 3.60 (2H, t, J =
6.5 Hz), 2.89 (1H, m), 2.34 (2H, m), 2.13 (1H, m), 1.55-1.26 (6H, m), 1.19 (9H, s), 0.89 (9H, s), 0.86 (9H,
s), 0.04 (12H, m); 13C-NMR (100 MHz, CDCl3) δ : 178.5, 131.6, 130.4, 73.5, 67.7, 63.0, 47.5, 45.6, 38.8,
35.3, 33.1, 32.8, 27.2, 26.0, 22.2, 18.3, 18.1, -3.9, -4.4, -5.3; ESIMS m/z: 535 (M++Na, 100); HRESIMS
m/z: 535.3618 (Calcd for C28H56O4NaSi2: M++Na, 535.3615).
(1S*,2S*,3S*,5R*)-3-[(1S*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-yl-
methyl 2,2-dimethylpropionate (15a) and (1R*,2S*,3S*,5S*)-3-[(1S*)-1,5-bis(tert-butyldimethyl-
siloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-ylmethyl 2,2-dimethylpropionate (15b). To a cold (0 °C)
solution of cyclopentene 14 (261 mg, 508 μmol) in CH2Cl2 (5.10 mL), were added Na2HPO4 (288 mg,
2.03 mmol) and 65% m-CPBA (202 mg, 762 μmol). After stirring for 1 h at rt, saturated aqueous Na2S2O3
was added and stirred for 30 min. The mixture was diluted with Et2O, washed with saturated aqueous
NaHCO3, water and saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (hexane : Et2O = 9 : 1) to give α-epoxide
15a (16.2 mg, 6% yield) and β-epoxide 15b (244 mg, 91% yield) as each colorless oil. 15a: IR (neat)
cm-1: 2931, 1733; 1H-NMR (400 MHz, CDCl3) δ : 4.11 (1H, dd, J = 11.1, 5.0 Hz), 3.93 (1H, dd, J = 11.1,
7.5 Hz), 3.68 (2H, t, J = 6.4 Hz), 3.52 (1H, m), 3.47 (1H, m), 3.36 (1H, d, J = 2.5 Hz), 2.31 (1H, m), 2.12
(1H, dd, J = 14.9, 2.3 Hz), 1.97 (1H, m), 1.79 (1H, ddd, J = 14.9, 9.8, 1.6 Hz), 1.52-1.30 (6H, m), 1.21

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(9H, s), 0.89 (9H, s), 0.88 (9H, s), 0.05 (12H, m); 13C-NMR (100 MHz, CDCl3) δ : 178.4, 75.0, 65.1, 63.2,
60.0, 58.8, 45.6, 41.7, 38.8, 34.7, 33.4, 29.1, 27.2, 26.0, 20.4, 18.3, 18.1, -3.9, -4.2, -5.3; ESIMS m/z: 551
(M++Na, 100); HRESIMS m/z: 551.3563 (Calcd for C28H56O5NaSi2: M++Na, 551.3564). 15b: IR (neat)
cm-1: 2931, 1732; 1H-NMR (400 MHz, CDCl3) δ : 4.24 (1H, dd, J = 10.8, 4.7 Hz), 4.02 (1H, dd, J = 10.7,
9.4 Hz), 3.67 (1H, m), 3.57 (1H, t, J = 6.4 Hz), 3.48 (2H, br s), 2.23 (1H, dt, J = 4.8, 9.1 Hz), 1.97 (1H, dd,
J = 13.7, 7.8 Hz), 1.84 (1H, dd, J = 13.7, 9.2 Hz), 1.56-1.23 (7H, m), 1.22 (9H, s), 0.89 (9H, s), 0.87 (9H,
13
s), 0.04 (12H, m); C-NMR (100 MHz, CDCl3) δ : 178.3, 70.8, 63.8, 62.9, 58.1, 56.5, 41.1, 39.8, 38.8,
36.2, 33.0, 27.2, 26.8, 26.0, 22.1, 18.3, 18.1, -3.9, -4.7, -5.3; ESIMS m/z: 551 (M++Na, 100); HRESIMS
m/z: 551.3591 (Calcd for C28H56O5NaSi2: M++Na, 551.3564).
(1S*,2S*,3S*,5R*)-3-[(1S*)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-yl-
methyl 2,2-dimethylpropiolate (15a). To a solution of alcohol 13 (93.0 mg, 233 μmol) in CH2Cl2 (2.30
mL), VO(acac)2 (6.2 mg, 23.3 μmol) and TBHP (3.68 M in CH2Cl2, 127 μL, 466 μmol) under argon
atmosphere. After stirring the mixture at rt for 3 h, excess of Me2S was added and stirring for 3 h. The
reaction mixture was diluted with Et2O and filtered through silica gel and concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt = 4 : 1) to give
α-epoxide (80.6 mg, 83% yield) as a colorless oil: IR (neat) cm-1: 3437, 2932, 1732; 1H-NMR (400 MHz,
CDCl3) δ : 4.12 (1H, dd, J = 11.1, 5.7 Hz), 4.01 (1H, dd, J = 11.1, 6.9 Hz), 3.59 (2H, t, J = 6.5 Hz), 3.56
(1H, br s), 3.47 (2H, s), 3.44 (1H, d, J = 2.6 Hz), 2.53 (1H, m), 2.20 (1H, dd, J = 14.9, 1.7 Hz), 2.06 (1H,
dd, J = 10.5, 2.0 Hz), 1.92 (1H, ddd, J = 14.9, 10.5, 1.6 Hz), 1.56-1.28 (6H, m), 1.20 (9H, s), 0.88 (9H, s),
13
0.03 (6H, s); C-NMR (100 MHz, CDCl3) δ : 178.3, 73.4, 64.7, 63.0, 60.3, 59.5, 45.3, 44.8, 38.8, 36.5,
32.8, 27.2, 26.8, 26.0, 22.3, 18.3, -5.3; ESIMS m/z: 437 (M++Na, 100); HRESIMS m/z: 437.2727 (Calcd
for C22H42O5NaSi: M++Na, 437.2699).
To a cold (-78 °C) solution of the above α-epoxide (1.26 g, 3.04 mmol) in CH2Cl2 (31.0 mL), were added
2,6-lutidine (3.54 mL, 30.4 mmol) and TBDMSOTf (768 mL, 3.34 mmol). After stirring for 10 min, Et3N
(1.00 mL) and saturated aqueous NaHCO3 were added and stirred for 20 min. The mixture was diluted
with Et2O, washed with water and saturated aqueous NaCl, dried over MgSO4, and concentrated under
reduced pressure. The residue was purified by silica gel column chromatography (hexane : Et2O = 7 : 1)
to give TBDMS ether 15a (1.41 g, 88% yield) as a colorless oil.
(6S*)-6-{(1S*,2S*,3S*,5R*)-2-[(1E,4Z)-Deca-1,4-dienyl]-6-oxabicyclo[3.1.0]hex-3-yl}tetrahydro-
pyran-2-one (3). Analogue 3 was synthesized from α-epoxide 15a according to the above synthetic
1
method of analogue 1 from α-epoxide 10a. 3: a colorless oil; IR (neat) cm-1: 2925, 1737; H-NMR (400
MHz, CDCl3) δ : 5.54 (1H, ddt, J = 15.3, 0.5, 6.2 Hz), 5.46 (1H, m), 5.33 (2H, m), 4.14 (1H, dt, J = 3.0,
10.4 Hz), 3.56 (1H, br s), 3.32 (1H, d, J = 2.5 Hz), 2.76 (2H, t, J = 6.7 Hz), 2.66 (1H, d, J = 8.2 Hz), 2.55
(1H, ddd, J = 17.2, 7.0, 6.7 Hz), 2.42 (2H, m), 2.12-1.78 (7H, m), 1.41-1.25 (7H, m), 0.89 (3H, t, J = 6.7

HETEROCYCLES, Vol. 77, No. 2, 2009
1201
Hz); 13C-NMR (100 MHz, CDCl3) δ : 172.0, 131.4, 130.7, 128.4, 126.4, 83.6, 61.1, 58.5, 48.6, 44.6, 31.5,
30.3, 29.4, 29.2, 28.4, 27.1, 26.5, 22.5, 18.1, 14.0; ESIMS m/z: 341 (M++Na, 100); HRESIMS m/z:
341.2068 (Calcd for C20H30O3Na: M++Na, 341.2093).
(6S*)-6-{(1R*,2S*,3S*,5S*)-2-[(1E,4Z)-Deca-1,4-dienyl]-6-oxabicyclo[3.1.0]hex-3-yl}tetrahydro-
pyran-2-one (4). Analogue 4 was synthesized from β-epoxide 15b according to the above synthetic
1
method of analogue 1 from α-epoxide 10a. 4: a colorless oil; IR (neat) cm-1: 2925, 1739; H-NMR (400
MHz, CDCl3) δ : 5.61 (1H, dt, J = 15.4, 6.2 Hz), 5.44 (3H, m), 4.23 (1H, dt, J = 11.7, 2.6 Hz), 3.45 (1H,
br s), 3.39 (1H, m), 2.78 (2H, t, J = 6.5 Hz), 2.70 (1H, t, J = 9.0 Hz), 2.60 (1H, m), 2.41 (1H, ddd, J =
17.7, 9.3, 7.4 Hz), 2.11 (1H, dd, J = 13.5, 7.5 Hz), 2.02 (2H, m), 1.95-1.70 (4H, m), 1.64-1.46 (2H, m),
1.36-1.25 (7H, m), 0.88 (3H, t, J = 6.6 Hz); 13C-NMR (100 MHz, CDCl3) δ : 171.8, 132.2, 131.1, 128.2,
126.8, 78.5, 60.2, 55.6, 44.7, 43.2, 31.5, 30.4, 29.5, 29.3, 27.5, 27.2, 27.1, 22.5, 18.8, 14.0; ESIMS m/z:
341 (M++Na, 100); HRESIMS m/z: 341.2111 (Calcd for C20H30O3Na: M++Na, 341.2093).
tert-Butyl{(1S,2E)-1-ethyl-3-iodoallyloxy}diphenylsilane (17). To a solution of (S)-pent-1-yn-3-ol (16)
(2.90 g, 34.4 mmol) in DMF (34.0 mL), were added imidazole (5.85 g, 86.0 mmol) and TBDPSCl (17.9
mL, 68.8 mmol) and stirred at rt for 12 h. The reaction mixture was diluted with Et2O, washed with
saturated aqueous NaHCO3, water and saturated aqueous NaCl, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt
24
= 25 : 1) to give TBDPS ether (9.20 g, 83% yield) as a colorless oil: [α]D -64.3˚ (c 1.20, CHCl3); IR
(neat) cm-1: 3306, 2932; 1H-NMR (400 MHz, CDCl3) δ : 7.77 (2H, m), 7.70 (2H, m), 7.38 (6H, m), 4.32
(1H, ddd, J = 7.0, 5.4, 2.1 Hz), 2.31 (1H, d, J = 2.1 Hz), 1.68 (2H, m), 1.09 (9H, s), 0.96 (3H, t, J = 7.4
13
Hz); C-NMR (100 MHz, CDCl3) δ : 136.0, 133.6, 129.7, 127.6, 84.9, 72.5, 64.9, 31.3, 26.9, 19.3, 9.0;
EIMS m/z: 265 (M+-tBu, 100); HREIMS m/z: 265.1044 (Calcd for C17H17OSi: M+-tBu, 265.1049).
To the above TBDPS ether (11.2 g, 34.7 mmol), was added catecholborane (5.55 mL, 52.1 mmol) at
80 °C. After stirring for 6 h, 10% aqueous solution of K2CO3 was added and stirred at rt for 3 h. The
mixture was diluted with Et2O, washed with water and saturated aqueous NaCl, dried over MgSO4, and
concentrated under reduced pressure. The residue was used next reaction without purification.
To a solution of the above crude product in Et2O (70.0 mL), were added NaOH (3 M in H2O, 34.7 mL,
104 mmol) and I2 (26.4 g, 104 mmol) at 0 °C. After stirring for 12 h, saturated aqueous Na2S2O3 was
added and stirred for 1 h. The mixture was diluted with Et2O, washed with water and saturated aqueous
NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel
column chromatography (hexane : AcOEt = 50 : 1) to give iodoalkene 17 (11.8 g, 75% yield (two steps))
19
1
as a colorless oil: [α]D -97.7˚ (c 1.50, CHCl3); IR (neat) cm-1: 2931; H-NMR (400 MHz, CDCl3) δ :
7.65 (4H, m), 7.38 (6H, m), 6.43 (1H, dd, J = 14.4, 6.8 Hz), 5.95 (1H, d, J = 14.4 Hz), 4.04 (1H, m), 1.49
13
(2H, m), 1.07 (9H, s), 0.80 (3H, t, J = 7.5 Hz); C-NMR (100 MHz, CDCl3) δ : 148.0, 135.8, 134.0,

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HETEROCYCLES, Vol. 77, No. 2, 2009
133.7, 129.7, 127.5, 29.9, 27.0, 19.4, 8.7; EIMS m/z: 393 (M+-tBu, 100); HREIMS m/z: 393.0162 (Calcd
for C17H18IOSi: M+-tBu, 393.0172).
tert-Butyl[(1S,2E)-1-ethyl-5-trimethylsilylpent-2-en-4-ynyloxy]diphenylsilane (18). To a solution of
iodoalkene 17 (10.7 mg, 23.7 μmol) in benzene (0.12 mL), were added PrNH2 (2.9 μL, 35.5 μmol) and
(Ph3P)4Pd (2.7 mg, 2.40 μmol) at rt. After stirring for 30 min, (trimethylsilyl)acetylene (5.0 μL, 35.5
μmol) and CuI (0.2 mg, 1.20 μmol) were added and stirred for 3 h. The reaction mixture was diluted with
Et2O, washed with saturated aqueous NH4Cl, water and saturated aqueous NaCl, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by silica gel column chromatography
25
(hexane : AcOEt = 20 : 1) to give enyne 18 (6.3 mg, 63% yield) as a colorless oil: [α]D -73.5˚ (c 1.11,
1
CHCl3); IR (neat) cm-1: 2932, 2133; H-NMR (400 MHz, CDCl3) δ : 7.65 (4H, m), 7.39 (6H, m), 6.15
(1H, dd, J = 15.9, 5.5 Hz), 5.64 (1H, dd, J = 15.9, 1.3 Hz), 4.20 (1H, m), 1.44 (2H, m), 1.08 (9H, s), 0.76
(3H, t, J = 7.4 Hz), 0.20 (9H, s); 13C-NMR (100 MHz, CDCl3) δ : 146.6, 135.8, 134.2, 133.8, 129.6, 127.5,
109.4, 103.7, 94.3, 74.2, 29.9, 27.0, 19.4, 8.4, 0.0; EIMS m/z: 421 (M+, 14), 363 (M+-tBu, 100); HREIMS
m/z: 363.1609 (Calcd for C22H27OSi2: M+-tBu, 363.1600).
(1S,2E)-1-Ethylpent-2-en-4-ynyl acetate (19). To a solution of enyne 18 (1.09 g, 2.59 mmol) in THF
(13.0 mL), was added TBAF (1.0 M in THF, 7.77 mL, 7.77 mmol) and stirred at rt for 2 h. The reaction
mixture was diluted with Et2O, washed with saturated aqueous NH4Cl, water and saturated aqueous NaCl,
dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel
column chromatography (hexane : Et2O = 2 : 1) to give alcohol (253 mg, 90% yield) as a colorless oil:
[α]D24 +6.9˚ (c 1.16, CHCl3); IR (neat) cm-1: 3290, 2935, 2103; 1H-NMR (500 MHz, CDCl3) δ : 6.24 (1H,
dd, J = 16.0, 5.8 Hz), 5.69 (1H, ddd, J = 16.0, 2.0, 1.7 Hz), 4.10 (1H, m), 2.88 (1H, d, J = 2.1 Hz), 1.69
13
(1H, br s), 1.57 (2H, m), 0.93 (3H, t, J = 7.5 Hz); C-NMR (125 MHz, CDCl3) δ : 147.3, 108.8, 81.6,
77.8, 73.3, 29.7, 9.4; EIMS m/z: 109 (M+-H, 31), 53 (100).
To a cold (0 °C) solution of the above alcohol (1.30 g, 11.8 mmol) in CH2Cl2 (59.0 mL), were added
DMAP (4.32 g, 35.4 mmol) and AcCl (1.68 mL, 23.6 mmol) stirred for 2 h. The reaction mixture was
diluted with Et2O, filtered through silica gel, washed with water and saturated aqueous NaCl, dried over
MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column
24
chromatography (hexane : Et2O = 3 : 1) to give acetate 19 (1.53 g, 86% yield) as a colorless oil: [α]D
1
-104.1˚ (c 0.63, CHCl3); IR (neat) cm-1: 3294, 2939, 2106, 1737; H-NMR (400 MHz, CDCl3) δ : 6.13
(1H, dd, J = 16.0, 6.5 Hz), 5.67 (1H, ddd, J = 16.0, 2.1, 1.4 Hz), 5.21 (1H, m), 2.90 (1H, d, J = 2.2 Hz),
2.06 (3H, s), 1.65 (2H, m), 0.90 (3H, t, J = 7.4 Hz); 13C-NMR (100 MHz, CDCl3) δ : 170.1, 142.6, 110.9,
81.2, 78.4, 74.6, 27.1, 21.1, 9.2; EIMS m/z: 152 (M+, 15), 43 (100).
(1S,2E,7E)-8-(1R,2S,3S,5S)-{3-[(S)-1,5-Bis(tert-butyldimethylsiloxy)pentyl]-6-oxabicyclo[3.1.0]hex-
2-yl}-1-ethylocta-2,7-dien-4-ynyl acetate (21) and (1S,2E,7E)-8-(1S,2R,3R,5R)-{3-[(R)-1,5-bis(tert-

HETEROCYCLES, Vol. 77, No. 2, 2009
1203
butyldimethylsiloxy)pentyl]-6-oxabicyclo[3.1.0]hex-2-yl}-1-ethylocta-2,7-dien-4-ynyl acetate (22).
To a solution of enyne 19 (213 mg, 1.40 mmol) in DMF (4.70 mL), were added K2CO3 (517 mg, 3.74
mmol), NaI (561 mg, 3.74 mmol), CuI (356 mg, 1.87 mmol) and allylic iodide 20 (543 mg, 935 μmol).
After stirring at rt for 4 h, the reaction mixture was diluted with Et2O, washed with saturated aqueous
NH4Cl, water and saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure.
The residue was purified by silica gel column chromatography (hexane : Et2O = 4 : 1) to give a
diastereomeric mixture of dienynes 21 and 22 (543 mg, 90% yield) as colorless oil. The mixture was used
1
next reaction without separation: IR (neat) cm-1: 2928, 1739; H-NMR (500 MHz, CDCl3) δ : 5.96 (1H,
dd, J = 15.8, 6.9 Hz), 5.70 (2H, m), 5.57 (1H, dt, J = 15.5, 5.5 Hz), 5.19 (1H, dt, J = 6.4, 6.3 Hz), 3.59
(1H, m), 3.57 (2H, t, J = 6.6 Hz), 3.44 (1H, m), 3.39 (1H, m), 3.08 (2H, d, J = 5.4 Hz), 2.50 (1H, t, J = 8.8
Hz), 2.05 (3H, s), 1.97 (1H, dd, J = 13.8, 7.6 Hz), 1.80 (1H, ddd, J = 13.8, 9.5, 1.0 Hz), 1.64 (2H, m),
1.57 (1H, m), 1.46 (3H, m), 1.36 (1H, m), 1.23 (2H, m), 0.90 (3H, t, J = 7.4 Hz), 0.89 (9H, s), 0.87 (9H,
13
s), 0.04 (3H, s), 0.04 (9H, s); C-NMR (125 MHz, CDCl3) δ : 170.2, 139.6, 131.1, 125.9, 112.6, 88.7,
79.9, 75.0, 70.1, 63.0, 60.3, 56.0, 44.9, 42.6, 36.4, 33.0, 27.2, 26.8, 26.0, 22.8, 21.8, 21.1, 18.3, 18.1, 9.3,
-3.7, -4.4, -5.3; ESIMS m/z: 627 (M++Na, 100); HRESIMS m/z: 627.3896 (Calcd for C34H60O5NaSi2:
M++Na, 627.3877).
(1S,2E,4Z,7E)-1-Ethyl-8-{(1R,2S,3S,5S)-3-[(S)-6-oxotetrahydropyran-2-yl]-6-oxabicyclo[3.1.0]hex-
2-yl}octa-2,4,7-trienyl acetate (23) and (1S,2E,4Z,7E)-1-Ethyl-8-{(1S,2R,3R,5R)-3-[(R)-6-oxotetra-
hydropyran-2-yl]-6-oxabicyclo[3.1.0]hex-2-yl}octa-2,4,7-trienyl acetate (24). To a solution of the
mixture of dienynes 21 and 22 (208 mg, 342 μmol) in DMF (1.70 mL), were added TBAF (1.0 M in THF,
1.71 mL, 1.71 mmol) and acetic acid (97.9 μL, 1.71 μmol). After stirring for 37 h at 60 °C, the reaction
mixture was diluted with AcOEt, washed with saturated aqueous NH4Cl, water and saturated aqueous
NaCl, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel
column chromatography (hexane : acetone = 1 : 1) to give a mixture of diols (72.9 mg, 56% yield) and a
mixture of mono TBDMS ethers (55.0 mg, 33% yield): diols: IR (neat) cm-1: 3418, 2935, 1734; 1H-NMR
(400 MHz, CDCl3) δ : 5.94 (1H, dd, J = 15.9, 6.8 Hz), 5.69 (2H, m), 5.57 (1H, dt, J = 15.3, 5.4 Hz), 5.15
(1H, m), 3.59 (2H, t, J = 6.2 Hz), 3.54 (1H, m), 3.43 (1H, m), 3.38 (1H, m), 3.05 (2H, d, J = 5.3 Hz), 2.57
(1H, t, J = 8.9 Hz), 2.22 (2H, br s), 2.03 (3H, s), 2.01 (1H, dd, J = 13.9, 7.6 Hz), 1.69 (1H, m), 1.62 (2H,
13
m), 1.56-1.30 (7H, m), 0.87 (3H, t, J = 7.4 Hz); C-NMR (100 MHz, CDCl3) δ : 170.3, 139.5, 130.7,
126.2, 112.5, 88.6, 79.9, 75.1, 69.4, 62.4, 60.2, 55.9, 45.1, 43.6, 35.9, 32.3, 27.1, 26.9, 22.6, 22.3, 21.1,
9.3; ESIMS m/z: 399 (M++Na, 40), 254 (100); HRESIMS m/z: 399.2139 (Calcd for C22H32O5Na: M++Na,
399.2147); TBDMS ethers: IR (neat) cm-1: 3446, 2931, 1739; 1H-NMR (400 MHz, CDCl3) δ : 5.95 (1H,
dd, J = 15.9, 6.9 Hz), 5.70 (2H, m), 5.56 (1H, dt, J = 15.4, 5.4 Hz), 5.17 (1H, m), 3.59 (3H, m), 3.43 (1H,
m), 3.37 (1H, m), 3.06 (2H, d, J = 5.3 Hz), 2.48 (1H, t, J = 8.7 Hz), 2.04 (3H, s), 1.96 (1H, dd, J = 13.8,

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HETEROCYCLES, Vol. 77, No. 2, 2009
7.5 Hz), 1.78 (1H, m), 1.68-1.42 (7H, m), 1.40-1.21 (3H, m), 0.89 (3H, t, J = 7.4 Hz), 0.86 (9H, s), 0.03
(3H, s), 0.03 (3H, s); 13C-NMR (100 MHz, CDCl3) δ : 170.3, 139.5, 131.1, 125.9, 112.6, 88.7, 79.9, 75.1,
70.0, 62.7, 60.3, 56.0, 44.9, 42.4, 36.3, 32.8, 27.2, 26.9, 25.9, 22.8, 21.7, 21.1, 18.1, 9.3, -3.8, -4.5;
ESIMS m/z: 513 (M++Na, 100); HRESIMS m/z: 513.3025 (Calcd for C28H46O5NaSi: M++Na, 513.3012).
To a solution of the above diols (72.9 mg, 192 μmol) in CH2ClCH2Cl (9.60 mL), were added MS 4A (96
mg), NMO (110 mg, 960 μmol) and TPAP (6.7 mg, 19.2 μmol). After stirring at rt for 30 min, the
reaction mixture was diluted with Et2O, filtered through silica gel and concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (hexane : AcOEt = 1 : 1) to give
1
a mixture of lactones (48.4 mg, 67% yield) as colorless oil: IR (neat) cm-1: 2930, 2880, 1736; H-NMR
(400 MHz, CDCl3) δ : 5.97 (1H, dd, J = 16.0, 6.8 Hz), 5.71 (2H, m), 5.63 (1H, dt, J = 15.3, 5.0 Hz), 5.18
(1H, m), 4.24 (1H, dt, J = 11.7, 2.5 Hz), 3.46 (1H, m), 3.40 (1H, m), 3.08 (2H, d, J = 4.9 Hz), 2.76 (1H, dt,
J = 0.9, 9.1 Hz), 2.60 (1H, m), 2.42 (1H, ddd, J = 17.8, 9.2, 7.4 Hz), 2.12 (1H, dd, J = 13.4, 7.4 Hz), 2.05
13
(3H, s), 1.93-1.72 (4H, m), 1.64 (3H, m), 1.52 (1H, m), 0.89 (3H, t, J = 7.4 Hz); C-NMR (100 MHz,
CDCl3) δ : 171.7, 170.2, 139.8, 129.9, 127.3, 112.5, 88.2, 80.2, 78.3, 75.0, 59.9, 55.6, 44.4, 43.0, 29.4,
27.3, 27.2, 27.1, 22.6, 21.1, 18.7, 9.3; ESIMS m/z: 395 (M++Na, 82), 327 (100); HRESIMS m/z: 395.1834
(Calcd for C22H28O4Na: M++Na, 395.1834).
A solution of the above lactones (28.2 mg, 75.3 μmol) in EtOH (1.50 mL) in the presence of 5% Pd on
BaSO4 (11.3 mg) and quinoline (14.1 μL) was stirred at rt for 16 h under a hydrogen atmosphere. The
reaction mixture was diluted with Et2O and filtered through silica gel and the filtrate was concentrated
under reduced pressure. The residue was purified by silica gel column chromatography (hexane : acetone
= 3 : 1) to give mixture of trienes. Trienens were separation by HPLC (CHIRALPAK AS-H, 0.46 cm x 25
cm, hexane : isopropanol = 82 : 18, flow rate: 2.0 mL/min) to give triene 23 (tR = 20.2 min, 5.4 mg, 19%
20
yield) and triene 24 (tR = 28.2 min, 5.0 mg, 17% yield); 23: [α]D -179.6˚ (c 0.52, CHCl3); IR (neat)
cm-1: 2924, 1734; 1H-NMR (400 MHz, CDCl3) δ : 6.49 (1H, dd, J = 15.2, 11.0 Hz), 6.01 (1H, t, J = 11.0
Hz), 5.63 (1H, dt, J = 15.4, 6.2 Hz), 5.60 (1H, dd, J = 15.5, 7.0 Hz), 5.48 (2H, m), 5.22 (1H, q, J = 6.8
Hz), 4.24 (1H, dt, J = 11.7, 2.6 Hz), 3.46 (1H, br s), 3.40 (1H, dd, J = 2.6, 1.4 Hz), 2.94 (2H, dd, J = 6.9,
6.8 Hz), 2.71 (1H, t, J = 8.9 Hz), 2.61 (1H, m), 2.42 (1H, ddd, J = 17.7, 9.2, 7.4 Hz), 2.12 (1H, dd, J =
13.5, 7.5 Hz), 2.06 (3H, s), 1.95-1.49 (7H, m), 0.90 (3H, t, J = 7.4 Hz); 13C-NMR (100 MHz, CDCl3) δ :
171.8, 170.4, 131.6, 131.2, 130.3, 129.0, 128.4, 127.7, 78.5, 75.9, 60.1, 55.6, 44.7, 43.2, 30.9, 29.5, 27.5,
27.5, 27.2, 21.3, 18.8, 9.5; ESIMS m/z: 397 (M++Na, 88), 315 (100); HRESIMS m/z: 397.1966 (Calcd for
24
C22H30O5Na: M++Na, 397.1991). 24: [α]D +165.2˚ (c 0.50, CHCl3); IR (neat) cm-1: 2925, 1733;
1H-NMR (400 MHz, CDCl3) δ : 6.49 (1H, dd, J = 15.3, 11.1 Hz), 6.01 (1H, t, J = 10.8 Hz), 5.64 (1H, dt, J
= 15.4, 6.1 Hz), 5.60 (1H, dd, J = 14.8, 7.4 Hz), 5.48 (2H, m), 5.21 (1H, q, J = 6.8 Hz), 4.24 (1H, dt, J =
11.7, 2.6 Hz), 3.46 (1H, br s), 3.40 (1H, dd, J = 2.6, 1.4 Hz), 2.94 (2H, dd, J = 7.5, 6.2 Hz), 2.72 (1H, t, J

HETEROCYCLES, Vol. 77, No. 2, 2009
1205
= 9.1 Hz), 2.61 (1H, m), 2.42 (1H, ddd, J = 17.8, 9.3, 7.8 Hz), 2.12 (1H, dd, J = 13.6, 7.5 Hz), 2.06 (3H,
13
s), 1.94-1.48 (7H, m), 0.90 (3H, t, J = 7.4 Hz); C-NMR (100 MHz, CDCl3) δ : 171.8, 170.4, 131.6,
131.2, 130.3, 129.0, 128.4, 127.7, 78.5, 75.8, 60.1, 55.6, 44.7, 43.1, 30.8, 29.5, 27.5, 27.5, 27.1, 21.3, 18.8,
9.5; ESIMS m/z: 397 (M++Na, 100); HRESIMS m/z: 397.1980 (Calcd for C22H30O5Na: M++Na,
397.1991).
Methyl (S)-5-hydroxy-5-{(1S,2R,3S,5S)-2-[(1E,4Z,6E,8S)-8-hydroxydeca-1,4,6-trienyl]-6-oxabicyclo-
[3.1.0]hex-3-yl}pentanoate (25). To a solution of lactone 23 (2.9 mg, 7.8 μmol) in MeOH (100 μL), was
added K2CO3 (3.2 mg, 23.4 μmol). After stirring at rt for 1 h, the reaction mixture was diluted with Et2O,
washed with saturated aqueous NH4Cl, water and saturated aqueous NaCl, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by silica gel column chromatography
20
(CHCl3 : MeOH = 25 : 1) to give ester 25 (1.7 mg, 60% yield) as colorless oil: [α]D -75.5˚ (c 0.02,
1
CHCl3); IR (neat) cm-1: 3419, 2923, 1732; H-NMR (400 MHz, CDCl3) δ : 7.45 (2H, m), 7.40 (3H, m),
5.15 (1H, m), 3.67 (3H, s), 3.54 (3H, s), 3.35 (1H, d, J = 2.6 Hz), 3.30 (1H, d, J = 2.8 Hz), 2.31 (2H, t, J =
2.8 Hz), 2.03 (1H, dd, J = 12.3, 6.0 Hz), 1.71 (1H, m), 1.59 (2H, m), 1.57 (1H, m), 1.54 (1H, m), 1.53
(1H, m), 1.42 (2H, m), 1.39 (1H, m), 1.26 (16H, m), 0.89 (3H, t, J = 7.0 Hz).
Methyl 5-[(1R,2R,3S,5S)-2-decyl-6-oxa-bicyclo[3.1.0]hex-3-yl]-5-[(S)-(3,3,3-trifluoro-2-methoxy-2-
phenylpropionyloxy]pentanoate ((S)-26). To a solution of alcohol 25 (1.7 mg, 4.7 μmol) in
CH2ClCH2Cl (800 μL), were added DMAP (34.0 mg, 282 μmol) and (S)-(+)-MTPA-Cl (26.2 μL, 141
μmol). After stirring at rt for 30 min, the reaction mixture was diluted with Et2O, washed with water and
saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The crude product
was used next reaction without purification.
A solution of the above crude ester in MeOH (200 μL) in the presence of 10% Pd on C (0.5 mg) was
stirred at rt for 2 h under a hydrogen atmosphere. The reaction mixture was diluted with Et2O and filtered
through silica gel and the filtrate was concentrated under reduced presser. The residue was purified by
silica gel thin layer chromatography (hexane : AcOEt = 3 : 1) to give (S)-MTPA ester (S)-26 (0.7 mg,
31
25% yield, two steps) as a colorless oil: [α]D -26.2˚ (c 0.45, CHCl3); IR (neat) cm-1: 2925, 2854, 1742;
1H-NMR (400 MHz, CDCl3) δ : 7.52 (2H, m), 7.40 (3H, m), 5.17 (1H, m), 3.66 (3H, s), 3.49 (3H, s), 3.39
(1H, d, J = 2.1 Hz), 3.35 (1H, d, J = 2.6 Hz), 2.28 (2H, t, J = 7.0 Hz), 2.06 (1H, dd, J = 13.1, 6.8 Hz),
1.65 (1H, m), 1.60 (1H, dd, J = 16.9, 7.5 Hz), 1.57 (1H, m), 1.54 (1H, m), 1.49 (1H, m), 1.45 (2H, m),
13
1.27 (18H, m), 0.88 (3H, t, J = 6.7 Hz); C-NMR (100 MHz, CDCl3) δ : 173.3, 166.2, 132.0, 129.6,
128.5, 127.5, 75.5, 58.6, 55.6, 55.3, 51.6, 42.4, 41.6, 33.4, 32.5, 31.9, 29.8, 29.6, 29.5, 29.3, 28.2, 27.9,
22.7, 20.9, 14.1; ESIMS m/z: 593 (M++Na, 88), 315 (10), 319 (100); HRESIMS m/z: 593.3068 (Calcd for
C31H45O6F3Na: M++Na, 593.3066).
Methyl 5-[(1R,2R,3S,5S)-2-decyl-6-oxa-bicyclo[3.1.0]hex-3-yl]-5-[(R)-(3,3,3-trifluoro-2-methoxy-2-

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HETEROCYCLES, Vol. 77, No. 2, 2009
phenylpropionyloxy]pentanoate ((R)-26). To a solution of alcohol 25 (0.9 mg, 2.5 μmol) in
CH2ClCH2Cl (400 μL), were added DMAP (18.1 mg, 148 μmol) and (R)-(-)-MTPA-Cl (14.0 μL, 74.1
μmol). After stirring at rt for 30 min, the reaction mixture was diluted with Et2O, washed with water and
saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The crude product
was used next reaction without purification.
A solution of the above crude ester in MeOH (100 μL) in the presence of 10% Pd on C (0.3 mg) was
stirred at rt for 2 h under a hydrogen atmosphere. The reaction mixture was diluted with Et2O and filtered
through silica gel and the filtrate was concentrated under reduced pressure. The residue was purified by
silica gel thin layer chromatography (hexane : AcOEt = 3 : 1) to give (R)-MTPA ester (R)-26 (0.9 mg,
31
64% yield, two steps) as a colorless oil: [α]D -61.1˚ (c 0.45, CHCl3); IR (neat) cm-1: 2925, 2854, 1743;
1H-NMR (400 MHz, CDCl3) δ : 7.54 (2H, m), 7.40 (3H, m), 5.17 (1H, m), 3.67 (3H, s), 3.54 (3H, s), 3.35
(1H, d, J = 2.6 Hz), 3.30 (1H, d, J = 2.8 Hz), 2.31 (2H, t, J = 2.8 Hz), 2.03 (1H, dd, J = 12.3, 6.0 Hz),
1.71 (1H, m), 1.59 (2H, m), 1.57 (1H, m), 1.54 (1H, m), 1.53 (1H, m), 1.42 (2H, m), 1.39 (1H, m), 1.26
13
(16H, m), 0.89 (3H, t, J = 6.7 Hz); C-NMR (100 MHz, CDCl3) δ : 173.3, 166.2, 132.2, 129.6, 128.4,
127.3, 75.3, 58.6, 55.7, 55.4, 51.6, 42.2, 41.4, 33.4, 32.6, 31.9, 29.9, 29.6, 29.6, 29.5, 29.4, 28.2, 27.6,
22.7, 21.1, 14.1; ESIMS m/z: 571 (M++H, 30), 319 (100); HRESIMS m/z: 571.3237 (Calcd for
C31H46O6F3: M++H, 571.3246).
(S)-6-{(1S,2S,3R,5S)-2-[(1E,4Z,6E,8S)-8-Hydroxydeca-1,4,6-trienyl]-6-oxabicyclo[3.1.0]hex-3-yl}-
tetrahydropyran-2-one (agadhilactone) (27). To a solution of lactone 23 (7.0 mg, 18.7 μmol) in THF
(400 μL), was added NaOH (1 M aqueous solution, 187 μL, 187 μmol). After stirring at rt for 4 h,
saturated aqueous NH4Cl was added. The reaction mixture was diluted with AcOEt, washed with water
and saturated aqueous NaCl, dried over MgSO4, and concentrated under reduced pressure. The crude
carboxylic acid was used next reaction without purification.
To a solution of the above crude carboxylic acid in CH2Cl2 (900 μL), were added DMAP (0.5 mg, 4.09
μmol) and DCC (4.6 mg, 22.3 μmol). After stirring at rt for 30 min, the reaction mixture was diluted with
Et2O, filtered through silica gel and concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (hexane : AcOEt = 2 : 3) to give agardhilactone (27) (5.0 mg, 90%
31
yield, two steps) as colorless oil: [α]D -104.4˚ (c 0.09, CHCl3); IR (neat) cm-1: 3442, 2958, 1733;
1H-NMR (400 MHz, CDCl3) δ : 6.49 (1H, m), 6.05 (1H, t, J = 11.0 Hz), 5.70 (1H, dd, J = 15.1, 6.8 Hz),
5.64 (1H, m), 5.42 (2H, m), 4.24 (1H, dt, J = 11.7, 2.8 Hz), 4.10 (1H, m), 3.46 (1H, br s), 3.40 (1H, m),
2.94 (2H, dd, J = 7.4, 6.3 Hz), 2.72 (1H, t, J = 8.9 Hz), 2.61 (1H, m), 2.42 (1H, ddd, J = 17.7, 9.2, 7.3 Hz),
2.12 (1H, dd, J = 13.5, 7.5 Hz), 1.94-1.70 (4H, m), 1.65-1.49 (5H, m), 0.94 (3H, t, J = 7.4 Hz); 13C-NMR
(100 MHz, CDCl3) δ : 171.8, 136.4, 131.3, 129.3, 129.0, 128.7, 125.5, 78.5, 74.0, 60.2, 55.7, 44.6, 43.2,

HETEROCYCLES, Vol. 77, No. 2, 2009
1207
30.9, 30.2, 29.5, 27.5, 27.2, 18.8, 9.7; ESIMS m/z: 355 (M++Na, 100); HRESIMS m/z: 355.1877 (Calcd
for C20H28O4Na: M++Na, 355.1885).
ACKNOWLEDGEMENTS
The authors are grateful to Prof. William H. Gerwick, Oregon State University, for providing the NMR
spectra of agardhilactone acetate. This work was supported in part by a Grant-in-Aid for Scientific
Research from The Ministry of Education, Culture, Sports, Science and Technology (MEXT) and
“High-Tech Research Center” Project for Private Universities: matching fund subsidy from MEXT.
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