Stereoselective synthesis of the left wing of Caribbean ciguatoxin

Article abstract of DOI:10.1016/j.tet.2011.05.080

Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are potent toxic polycyclic ethers. In this paper, we report a stereoselective and secure route to the left wing of Caribbean ciguatoxin on the basis of a 6-exo radical cyclizatio

Full text of DOI:10.1016/j.tet.2011.05.080

Tetrahedron 67 (2011) 6616e6626
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stereoselective synthesis of the left wing of Caribbean ciguatoxin
*
*
Shuji Yamashita , Ryohei Uematsu, Masahiro Hirama
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 April 2011
Received in revised form 17 May 2011
Accepted 18 May 2011
Available online 26 May 2011
Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are potent toxic polycyclic
ethers. In this paper, we report a stereoselective and secure route to the left wing of Caribbean ciguatoxin
on the basis of a 6-exo radical cyclization strategy.
Ó 2011 Elsevier Ltd. All rights reserved.
This paper is dedicated to Professor Satoshi
ꢀ
Omura on the occasion of the 2010 Tetra-
hedron Prize
Keywords:
Caribbean ciguatoxin
Polycyclic ether
Convergent synthesis
Radical cyclization
1. Introduction
Me
Ciguatera seafood poisoning, an important medical issue in
tropical and subtropical regions, causes gastrointestinal, cardio-
vascular, and neurological disorders that may last for weeks or even
years.1 Alhough ciguatera had been localized to the islands of the
Pacific Ocean, Indian Ocean, and the Caribbean Sea, it has become
a global problem due to expanding tourism and trade. Ciguatoxins
(CTXs), the principal causative toxins of ciguatera, are ladder-like
polycyclic ethers 3 nm in length with ring sizes ranging from
five- to nine-members.2 Ciguatoxins exhibit their potent toxicities
HO
H
Me
H
J
O
I
O
H
K
H
H
H
H
HO
G
H
H
H
H
H
H
O
O
O
OH
Me
O
B
E
H
O
H
H
F
A
C
O
D
H
H
O
O
H
O
H
H
1
O
H
L
23
C-CTX-1 (1)
Me
M
O
H
Me
O
N
Me
I
OH
HO
Me
H
(LD50¼0.25e4
mg/kg, mice) by binding to the voltage-sensitive
H
J
57
O
OH
sodium channels (VSSC) of excitable membranes.3,4 Recent prog-
ress in analytical technology reveals that the ciguatoxins are
structurally varied according to geographical region.5 Caribbean
ciguatoxin C-CTX-1 (1, Fig. 1) was isolated from the carnivorous fish
horse-eye jack (Caranx latus) as the main toxin of ciguatera in the
Caribbean Sea.5a In contrast to the typical Pacific ciguatoxins,
CTX3C (2) and 51-hydroxyCTX3C (3),6 1 possesses 14 ether rings
with a more complicated architecture.
O H
Me
H
H
H
H
G
O
H
H
H
H
H
H
O
O
OH
O
B
E
H
O
H
H
K
H
O
F
D
A
C
O
H
H
O
O
H
Me
H
H
1
O
L
O
M
52
OH
CTX3C (2):
51-hydroxyCTX3C (3):
R
R
1 = H
1 = OH
Me
R1
Fig. 1. Structures of ciguatoxins.
We have successfully synthesized three Pacific ciguatoxins
immunosorbent assay (ELISA) for their detection.8,9 Moreover, we
have reported the syntheses of ABCDE-,10 M-,11 and LMN-ring12
fragments of 1. However, more practical and secure methods to
prepare sufficient amounts of the fragments are still required for
the total synthesis of 1. Recently, we developed three efficient
routes for constructing trans-fused polyethers based on radical
(2, 3, and CTX1B)7 and developed a sandwich enzyme-linked
* Corresponding authors. Tel.: þ81 22 795 6564; fax: þ81 22 795 6566; e-mail
addresses: s-yamashita@m.tohoku.ac.jp (S. Yamashita), hirama@m.tohoku.ac.jp
(M. Hirama).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.080

S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
6617
1) NaH, CS2
imidazole
THF, RT;
MeI, RT
reactions: (i) an acyl radical cyclization/reductive etherification
sequence,13 (ii) a 7-exo radical cyclization using an electron-
deficient acrylate/ring-closing olefin metathesis (RCM) se-
quence,7,14 and (iii) a 6-exo radical cyclization using a cis-vinyl
sulfoxide/RCM sequence.7h Herein, we describe an advanced syn-
thetic route to the left wing of 1 utilizing method (iii) as the key
strategy.
H
H
H
H
H
H
H
H
H
H
O
O
B
O
B
ref. 15
OAc
OAc
O
O
A
A
O
MP
O
MP
O
O
OAc
OH
OC(S)SMe
9
10
11
2) aq. H3PO2, AIBN
Et3N, dioxane, reflux
3) CSA, MeOH, RT
MP =
81%
OMe
2. Results and discussion
(3 steps)
m-CPBA
CH2Cl2
-25 to 0 °C
A new synthesis plan of the left wing (4) of 1 is summarized in
Scheme 1. The seven-membered D-ring was retrosynthetically
cleaved to triene 5, which could be generated from O,Se-acetal 6 by
the key 6-exo radical cyclization. The intermediate 6 would be
prepared from bicycles 7 and 8 via esterification and O,Se-acetal
formation.
H
H
H
H
H
O
B
TBSCl, imidazole
DMF, RT
O
B
OH
OTBS
A
A
96%
OH
H
OTBS
O
O
H
H
13
12
H
O
B
H
H
H
H
H
H
O
B
H
O
O
H
NAPO
OTBS
OTBS
OTBS
H
H
H
OH
O
A
A
O
B
E
+
OTBS
A
C
D
O
O
O
H
H
H
O
O
H
H
H
14: 80%
15: 16%
Scheme 2. Synthesis of epoxide 14.
ring-closing
left wing of C-CTX (4)
olefin metathesis
H
H
NAPO
H
H
H
H
H
O
O
O
B
E
MP
A
C
O
Table 1
O
6-exo radical
cyclization
H
H
O
O
Regioselective cleavage of epoxide 14
H
HO
H
H
H
H
H
O
5
H
O
B
O
B
H
O
NAPO
3
H
H
H
OTBS
see below
O
O
O
O
B
E
A
A
HO
2
A
B
+
MP
A
OTBS
O
O
O
O
SePh
H
H
H
17
H
H
O
S
O
14
16
inseparable
H
O
OTBDPS
esterification &
NAPBr, NaH
TBAI, THF
DMF, RT
6
O,Se-acetal formation
NAPO
H
H
H
H
H
H
H
p-Tol
O
B
O
B
OTBS
OTBS
OTBS
H
H
A
NAPO
A
NAPO
H
H
H
+
O
HO
E
O
B
MP
OTBS
NAP =
O
O
CO2H
H
A
+
O
O
H
H
18: 65%
19: 17%
OTBS
O
H
OTBDPS
Combined Yield 16:17a
7
8
Entry
Conditions
LiBHEt3, THF, −20 °C
1
2
3
4
5
95%
41%
1:1
1:1
1:1
−
Scheme 1. Retrosynthesis of the left wing of C-CTX-1 (1).
LiBH(s-Bu)3, THF, −20 °C to RT
Red-Al,THF, −20 to 0 °C
DIBAL, CH2Cl2, 0 °C
17%
We first improved the synthesis of the AB-ring of C-CTX-1 from
the known alcohol 10, which was prepared from tri-O-acetyl-
decomposed
100%
LiAlH4, Et2O, −30 to −20 °C
4:1
D
-glucal 9 (Scheme 2).15 Deoxygenation of the B-ring alcohol of 10
was achieved by Barton radical reduction.16 Successive treatment of
10 with NaH, carbon disulfide, and MeI afforded xanthate 11. Re-
moval ofxanthate bythe actionof aqueous phosphinic acidandAIBN
in the presence of Et3N in dioxane furnished the C-CTX-1type B-ring.
Subsequent acid treatment to cleave the anisylidene acetal moiety
provided diol 12 in 81% overall yield from 10. After TBS protection of
the two hydroxy groups of 12, epoxidation of the resulting TBS ether
a
The ratio of 16:17 was determined by 1H-NMR analysis
alcohol 20 (Scheme 3). Following the method developed by Sam-
muelsson,18 the hydroxy group of 20 was converted to the iodide 21
in 93% yield from 18. After the one carbon homologation of 21 by
substitution of iodide with sodium cyanide, nitrile 22 was trans-
formed to the carboxylic acid 7 through DIBAL reduction and Pin-
nick oxidation in 85% overall yield from 21. The TES-protected
AB-ring carboxylic acid 24 was also prepared from 7 in two steps.
As shown in Scheme 4, the AB-ring carboxylic acid 7 was con-
densed with the E-ring alcohol 87h by Yamaguchi esterification19 to
afford ester 25a. The ester was treated with DIBAL in CH2Cl2 at
ꢀ90 ꢁC followed by acetylation with Ac2O and DMAP to produce
acetate 26a of the hemiacetal.20 The acetate group of 26a was
substituted with the phenylselenyl group by the action of
i-Bu2AlSePh, which was freshly prepared from DIBAL and (PhSe)2,21
to give O,Se-acetal 27a in 57% yield. Although selective removal of
the TBS group of 27a was attempted, cleavage of the TBDPS ether
always occurred competitively. We thus examined protection of the
primary alcohol of the corresponding diol 28. Although a variety of
experimental conditions was tested, including treatment of 28 with
13 with m-CPBA in CH2Cl2 at low temperature afforded
in 80% yield along with its diastereomer 15 (16%).
a-epoxide 14
Reductive opening of epoxide 14 was explored as summarized in
Table 1. Treatment of 14 with lithium triethylborohydride (LiBHEt3)
gave an inseparable 1:1 mixture of the desired C3-alcohol 16 and its
regioisomer 17 in 95% yield (entry 1). L-Selectride [LiBH(s-Bu)3],
Red-Al [NaAlH2(OCH2CH2OCH3)2], and DIBAL gave unsatisfactory
results (entries 2e4). After considerable experimentation we
eventually found that treatment of 14 with LiAlH4 in Et2O at ꢀ30 to
ꢀ20 ꢁC provided 16 as the major product (4:1) in 100% combined
yield. The secondary alcohols, 16 and 17, were protected as
2-naphthylmethyl (NAP)7b,17 ethers to give 18 and 19, which were
isolated in 65% and 17% yields, respectively.
Selective cleavage of the less-hindered TBS ether of 18 was
achieved by exposure to CSA in MeOH at 0 ꢁC to give primary

6618
NAPO
S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
NAPO
1.1 or 2.0 equiv of TBDPSCl in the presence of imidazole (Scheme 4,
entries 1 and 2), the desired secondary alcohol 29 was obtained in
only 30e32% yield. Based on these unsuccessful protecting group
manipulations, we decided to alter the TBS-protecting group of the
secondary alcohol on the B-ring to the more labile TES group. The
TES derivative 27b was prepared from 24 and 8 following the same
reaction sequence described above. Treatment of 27b with TBAF
at ꢀ30 ꢁC selectively cleaved the TES ether and gave secondary
alcohol 29 in 95% yield (Scheme 4, entry 3).
CSA, MeOH
THF, 0 °C
H
H
H
H
H
H
H
O
B
O
B
OTBS
OTBS
OH
A
A
95%
OTBS
O
O
H
18
20
I2, imidazole
PPh3, THF
0 °C to RT
98%
H
NAPO
NAPO
H
H
H
H
H
NaCN, DMSO
45 °C
O
B
O
B
CN
I
A
A
With the requisite 29 in hand, construction of the C- and D-rings
was performed (Scheme 5). The reaction of acetylene sulfoxide 3022
with the alkoxide, which was generated from alcohol 29 and NaH,
furnished the cis-vinyl sulfoxide 6 in 65% yield along with starting
material 29 (30%). It is noteworthy that the addition of 1 equiv of
H2O improved the yield as well as reproducibility, while the re-
action in the absence of H2O gave 6 in 8e54% yield and recovered
29 in 35e90% yield.23 Radical cyclization to construct the C-ring
was carried out under the previously optimized conditions.7h,24
Treatment of 6 with n-Bu3SnH and Et3B at low temperature affor-
ded the six-membered ether 31 exclusively in 70% yield. Sulfoxide
31 was converted to the terminal olefin 32 via Pummerer rear-
rangement25 and subsequent Wittig olefination. After cleavage of
the TBDPS ether by TBAF, alcohol 33 was transformed to phenyl-
selenide 34 using PhSeCN and n-Bu3P in THF. Oxidation of selenide
34 with hydrogen peroxide in the presence of NaHCO3 provided the
98%
OTBS
OTBS
O
O
H
H
22
21
DIBAL, CH2Cl2
-78 °C
NaClO2
96%
NaH2PO4·2H2O
2-methyl-2-butene
t-BuOH, H2O, RT
NAPO
NAPO
H
H
H
H
H
H
H
O
B
O
B
CHO
OTBS
CO2H
OR
A
A
90%
O
O
H
1) TBAF, THF, RT
2) TESCl, imidazole
DMF, RT
23
7: R = TBS
24: R = TES
83% (2 steps)
Scheme 3. Synthesis of the AB-ring.
corresponding selenoxide, which underwent b
-elimination at 40 ꢁC
to furnish the triene 5 in 82% yield from 32. RCM reaction of 5 using
Grubbs’ first generation catalyst (35)26 formed the seven-
membered D-ring, and acid treatment gave diol 36. Selective
tosylation of the primary alcohol of 36 followed by cyanation
afforded nitrile 37 in 78% yield. Synthesis of the left wing fragment
4 was finally accomplished from 37 by DIBAL reduction and Wittig
olefination in 72% yield for the two steps.
Cl
O
Cl
Cl
Cl
Et3N, DMAP
toluene, RT
H
H
E
NAPO
H
H
H
O
HO
O
B
MP
CO2H
A
+
O
O
OR1
H
H
O
H
OTBDPS
8 (1.0 eq)
7: R1 = TBS (1.2 eq)
3. Conclusion
24: R1 = TES (1.3eq)
H
We have devised a practical and stereoselective route to
construct the C-CTX-1 left wing. The features of the present syn-
thesis are (i) an improved preparation of the AB-ring, (ii) an effi-
cient coupling of the AB- and the E-rings through Yamaguchi
esterification followed by O,Se-acetal formation, (iii) a completely
stereocontrolled construction of the C-ring via 6-exo radical cycli-
zation using cis-vinyl sulfoxide, and (iv) RCM reaction to build the
seven-membered D-ring. The new method enabled us to synthe-
size 4 via 39 steps in 0.62% overall yield from commercially avail-
able materials (cf. previous synthesis: 39 steps in 0.25%).10 The left
wing prepared herein will play a key role in the total synthesis of
C-CTX-1, which is currently under investigation in our laboratory.
H
NAPO
DIBAL
H
H
O
O
O
B
E
MP
CH2Cl2, -90 °C;
A
O
O
O
H
H
O
Ac2O, DMAP
-90 to -35 °C
H
OR1
OTBDPS
25a: R1 = TBS, quant from 8
25b: R1 = TES, 94% from 24
H
H
NAPO
i-Bu2AlSePh
CH2Cl2, 0 °C
H
H
H
O
O
O
B
E
MP
A
O
O
OAc
H
H
O
OR1
OTBDPS
26a: R1 = TBS, 77%
26b: R1 = TES, 93%
H
H
NAPO
H
H
O
O
O
B
E
MP
4. Experimental
see below
A
O
O
SePh
H
H
O
OR1
OR2
H
4.1. General experimental procedures
27a: R1 = TBS, R2 = TBDPS, 57%
27b: R1 = TES, R2 = TBDPS, 86%
28: R1, R2 = H
TBAF, THF
reflux, quant
All reactions sensitive to air or moisture were carried out under
argon or nitrogen atmosphere in dry, freshly distilled solvents
under anhydrous conditions, unless otherwise noted. Chemical
H
H
NAPO
H
H
H
O
O
O
B
E
MP
A
shifts of NMR spectra are reported in
d (ppm) down field from
O
O
SePh
H
H
OH
tetramethylsilane with reference to solvent signals [1H NMR: CHCl3
(7.26), C6D5H (7.16), 13C NMR: CDCl3 (77.0), C6D6 (128.0)]. Signal
patterns are indicated as s, singlet; d, doublet; t, triplet; q, quartet;
m, multiplet; br, broad peak.
O
H
OTBDPS
29
Entry
Conditions
Results
1 (28)
2 (28)
TBDPSCl (1.1 eq), imidazole, DMF, RT
TBDPSCl (2.0 eq), imidazole, DMF, 0 °C
TBAF, THF, -30 °C
29: 32%, 28: 60%
29: 30%, 28: 20%
29: 95%
4.1.1. Diol 12. To a solution of alcohol 10 (930 mg, 2.78 mmol) in
THF (19 mL) were added NaH (60% in oil, 278 mg, 6.95 mmol) and
imidazole (95 mg, 1.39 mmol) at room temperature. After being
3 (27b)
Scheme 4. Coupling of the AB- and the E-rings.
stirred for 30 min, the mixture was added CS2 (420 mL, 6.95 mmol) at

S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
6619
n-Bu3SnH
Et3B
30, NaH
THF, H2O
0 °C to RT
H
H
H
H
H
NAPO
NAPO
toluene
H
H
H
H
H
H
H
H
H
NAPO
H
H
H
H
O
O
O
O
O
B
E
O
B
E
O
O
O
B
E
MP
MP
-78 to -40 °C
MP
A
A
C
A
O
O
O
O
SePh
O
O
65%
SePh
H
H
70%
H
H
O
S
O
H
H
O
O
O
OH
H
O
H
O
OTBDPS
OTBDPS
OTBDPS
S
O
p-Tol
(S)
S
p-Tol
29
6
31
p-Tol
1) TFAA, pyridine, MeCN, 0 °C;
KOAc, H2O, RT
2) Ph3PCH3Br, NaHMDS, THF
0 °C to RT
30
71% (2 steps)
H2O2
PhSeCN
NAPO
THF, RT
H
O
H
H
H
E
H
H
NAPO
NAPO
NaHCO3
n-Bu3P
H
H
H
H
H
H
H
H
H
H
H
H
H
H
O
O
O
O
O
O
B
E
O
B
E
O
B
MP THF, 40 °C
MP
MP
A
C
A
A
C
C
O
O
O
O
O
O
82%
H
H
H
H
quant
H
H
O
O
H
O
O
O
O
H
H
H
SePh
OR
PCy3
Ru
PCy3
34
32: R = TBDPS
33: R = H
5
TBAF
Cl
Cl
THF, 35 °C
quant
Ph
1) 35, CH2Cl2, reflux
2) CSA, MeOH
THF, RT
76%
35
1) DIBAL, CH2Cl2
-78 °C
2) Ph3PCH3Br
NaHMDS, THF
0 °C to RT
(2 steps)
1) TsCl, pyridine
RT
H
H
H
2) NaCN, DMSO
40 °C
H
H
H
H
NAPO
NAPO
NAPO
H
H
H
H
H
H
H
H
H
H
H
H
OH
OH
OH
OH
O
O
O
O
B
E
O
B
E
O
B
E
A
A
A
C
D
C
D
C
D
O
O
O
CN
78%
72%
H
H
H
H
H
H
O
O
H
O
O
O
O
(2 steps)
(2 steps)
H
H
H
H
36
37
Scheme 5. Synthesis of the left wing of Caribbean ciguatoxin.
4
room temperature. After being stirred for 40 min, the reaction
mixture was treated with MeI (517 L, 8.28 mmol). After being
4.1.2. Bis-TBS ethers 13. To a mixture of diol 12 (9.22 g, 46 mmol)
and imidazole (11.1 g, 161 mmol) in DMF (92 mL) was added TBSCl
(20.8 g, 138 mmol) at room temperature. After being stirred for
12 h, the mixture was quenched with saturated aqueous NaHCO3
and extracted with hexane and EtOAc (1:1). The combined organic
layer was washed with brine and dried over Na2SO4. Concentration
and column chromatography (hexane/EtOAc 1:0e5:1) afforded bis-
m
stirred for 1 h, the mixture was treated with saturated aqueous
NH4Cl and extracted with EtOAc. The organic layer was washed with
brine and dried over Na2SO4. Concentration and purification by
column chromatography (hexane/EtOAc 1:1) afforded xanthate 11,
which was used in the next reaction without further purification.
To a mixture of 11 (w2.78 mmol) and Et3N (5.83 mL, 41.7 mmol)
in dioxane (28 mL) and H2O (2 mL) were added H3PO2 (1.2 mL,
27.8 mmol) and AIBN (457 mg, 2.78 mmol). After being stirred for
5 h at 90 ꢁC, additional reagents (Et3N, 5.8 mL; H2O, 1.8 mL; H3PO2,
1.2 mL; AIBN, 457 mg) were added. After being stirred for 3 h at
90 ꢁC, the mixture was cooled to room temperature, quenched with
brine, and extracted with EtOAc. The combined organic layer was
dried over Na2SO4 and concentrated. Filtration through the pad of
silica gel (hexane/EtOAc 10:1e3:1) gave crude product, which was
used in the next reaction without further purification.
TBS ethers 13 (18.9 g, 44 mmol) in 96% yield: colorless amorphous;
22
D
[a
]
þ 41.4 (c 1.01, CHCl3); IR (film)
n
2952, 2929, 2856, 1471,1462,
;
1252, 1146, 1096, 1059, 836, 776 cmꢀ1
1H NMR (400 MHz, CDCl3)
d
5.95e5.82 (2H, m, H2, H3), 4.20 (1H, dd, J¼14.7, 5.9 Hz, H1), 3.98
(1H, ddd, J¼14.7, 2.0, 2.0 Hz, H1), 3.83 (1H, dd, J¼11.3, 1.7 Hz, H10),
3.70 (1H, dd, J¼11.3, 4.9 Hz, H10), 3.62 (1H, ddd, J¼11.0, 9.0, 4.7 Hz,
H8), 3.24 (1H, ddd, J¼11.0, 8.8, 4.7 Hz, H6), 3.10e3.05 (2H, m, H5,
H9), 2.57 (1H, ddd, J¼15.9, 8.2, 3.5 Hz, H4), 2.36e2.26 (2H, m, H4,
H7), 1.54 (1H, ddd, J¼11.0, 11.0, 11.0 Hz, H7), 0.89 (9H, s, TBS), 0.87
(9H, s, TBS), 0.07 (6H, s, TBS), 0.05 (6H, s, TBS); 13C NMR (100 MHz,
To a solution of tricyclic compound (w2.78 mmol) in MeOH
CDCl3) d 132.0 (CH, C2), 128.8 (CH, C3), 82.52 (CH, C6), 82.46 (CH,
(140 mL) was added CSA (194 mg, 834
After being stirred for 2 h, the mixture was treated with Et3N
(800 L) and concentrated. Purification by column chromatography
(hexane/EtOAc 4:1e1:3) gave diol 12 (453 mg, 2.26 mmol) in
m
mol) at room temperature.
C9), 77.52 (CH, C5), 67.60 (CH2, C1), 66.15 (CH, C8), 62.91 (CH2, C10),
41.14 (CH, C7), 34.65 (CH2, C4), 26.11 (CH3 ꢂ3, TBS), 25.89 (CH3 ꢂ3,
TBS), 18.64 (C, TBS), 18.07 (C, TBS), ꢀ4.21 (CH3, TBS), ꢀ4.78 (CH3 ꢂ2,
TBS), ꢀ5.01 (CH3, TBS); HRESIMS m/z 451.2670 [MþNa]þ (calcd for
C22H44NaO4Si2 451.2670).
m
22
81% from 10: colorless oil; colorless solid; mp 196 ꢁC; [
(c 1.01, CHCl3); IR (film) 3357, 2943, 2863, 1426, 1277, 1129, 1097,
1083, 1052, 1030, 1017, 707, 619 cmꢀ1 1H NMR (400 MHz, CDCl3)
5.94 (1H, dddd, J¼14.5, 6.3, 3.7, 3.7 Hz, H2), 5.86 (1H, dddd, J¼14.5,
a]
þ 17.2
D
n
;
4.1.3. Epoxide 14. To a solution of 13 (7.59 g, 17.7 mmol) in CH2Cl2
(350 mL) was added m-CPBA (70% purity, 10.7 g, 43 mmol) at
ꢀ25 ꢁC. After being stirred for 6 h at 0 ꢁC, m-CPBA (3.25 g,
13.2 mmol) was added and the mixture was stirred for additional
10 h. The reaction mixture was treated with saturated aqueous
NaHCO3 and Na2S2O3. The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
chromatography (hexane/EtOAc 50:1e10:1) gave epoxide 14
d
8.0, 3.1, 3.1 Hz, H3), 4.22 (1H, dd, J¼14.9, 6.3 Hz, H1), 3.99 (1H, ddd,
J¼1.9, 3.7, 3.1 Hz, H1), 3.86 (1H, dd, J¼11.5, 4.1 Hz, H10), 3.76 (1H, dd,
J¼11.5, 5.1 Hz, H10), 3.68 (1H, ddd, J¼11.3, 9.4, 4.7 Hz, H8), 3.31 (1H,
ddd, J¼11.3, 8.8, 4.7 Hz, H6), 3.20 (1H, ddd, J¼9.4, 5.1, 4.1 Hz, H9), 3.14
(1H, ddd, J¼10.6, 8.8, 3.7 Hz, H5), 2.57 (1H, ddd, J¼15.8, 8.4, 3.7 Hz,
H4), 2.42 (1H, ddd, J¼1.3, 4.7, 4.7 Hz, H7), 2.34 (1H, dddd, J¼15.8,
10.6, 3.7, 3.1 Hz, H4), 1.92 (2H, br, OH ꢂ2), 1.57 (1H, ddd, J¼11.3, 11.3,
(6.30 g, 14.1 mmol) in 80% yield along with its diastereomer 15
19
11.3 Hz, H7); 13C NMR (100 MHz, CDCl3)
d
132.1 (CH, C2), 128.3 (CH,
(1.29 g, 2.89 mmol) in 16% yield. 14: colorless solid; mp 84 ꢁC; [
a]
D
C3), 82.11 (CH, C6), 80.77 (CH, C9), 77.73 (CH, C5), 67.67 (CH2, C1),
66.91 (CH, C8), 63.18 (CH2, C10), 40.31 (CH2, C1), 34.42 (CH2, C4);
HRESIMS m/z 223.0940 [MþNa]þ (calcd for C10H16NaO4 223.0941).
þ 29.9 (c 1.01, CHCl3); IR (film)
1100,1075, 837, 776 cmꢀ1; 1H NMR (400 MHz, CDCl3)
J¼14.5, 3.3 Hz, H1), 3.81 (1H, dd, J¼11.3, 1.8 Hz, H10), 3.78 (1H, dd,
n
2953, 2928, 2855, 1472, 1251, 1144,
d
4.36 (1H, dd,

6620
S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
J¼14.5, 14.5 Hz, H1), 3.66 (1H, dd, J¼11.3, 4.9 Hz, H10), 3.53 (1H,
ddd, J¼11.4, 9.0, 4.7 Hz, H8), 3.25 (1H, ddd, J¼11.0, 9.0, 4.5 Hz, H5),
3.20 (1H, dd, J¼4.5, 4.5 Hz, H3), 3.02e2.98 (2H, m, H2, H9), 2.78 (1H,
ddd, J¼11.4, 9.0, 4.7 Hz, H6), 2.74 (1H, ddd, J¼15.3, 4.5, 4.5 Hz, H4),
2.25 (1H, ddd, J¼11.4, 4.7, 4.7 Hz, H7), 1.93 (1H, dd, J¼15.3, 11.0 Hz,
H4), 1.50 (1H, ddd, J¼11.4, 11.4, 11.4 Hz, H7), 0.88 (9H, s, TBS), 0.86
(9H, s, TBS), 0.05 (6H, s, TBS), 0.04 (6H, s, TBS); 13C NMR (100 MHz,
837, 776 cmꢀ1; 1H NMR (400 MHz, CDCl3)
d 7.84e7.78 (4H, m, NAP),
7.50e7.45 (3H, m, NAP), 4.74 (1H, d, J¼12.3 Hz, NAP), 4.71 (1H, d,
J¼12.3 Hz, NAP), 3.99 (1H, ddd, J¼12.9, 6.1, 3.9 Hz, H1), 3.89 (1H,
dddd, J¼8.6, 7.0, 4.9, 3.5 Hz, H3), 3.80 (1H, ddd, J¼11.4, 6.7, 3.0 Hz,
H10), 3.62e3.54 (3H, m, H5, H8, H10), 3.52 (1H, ddd, J¼12.9, 9.0,
2.9 Hz, H1), 3.18 (1H, ddd, J¼11.3, 5.7, 3.0 Hz, H9), 3.15 (1H, ddd,
J¼11.6, 9.2, 4.5 Hz, H6), 2.37 (1H, ddd, J¼14.7, 4.9, 3.9 Hz, H4), 2.27
(1H, ddd, J¼11.6, 4.5, 4.5 Hz, H7), 2.12 (1H, dddd, J¼15.0, 8.6, 6.1,
2.9 Hz, H2), 1.99 (1H, dddd, J¼15.0, 9.0, 7.0, 3.9 Hz, H2), 1.94 (1H, m,
OH), 1.90 (1H, ddd, J¼14.7, 9.4, 3.5 Hz, H4), 1.57 (1H, ddd, J¼11.6,
11.6, 11.6 Hz, H7), 0.87 (9H, s, TBS), 0.08 (3H, s, TBS), 0.07 (3H, s,
CDCl3)
d 82.10 (CH, C9), 80.55 (CH, C6), 76.54 (CH, C5), 66.25 (CH2,
C1), 65.62 (CH, C8), 62.74 (CH2, C10), 55.55 (CH2, C2), 52.65 (CH2,
C3), 40.53 (CH, C7), 33.67 (CH, C4), 26.08 (CH3 ꢂ3, TBS), 25.86 (CH3
ꢂ3, TBS), 18.61 (C, TBS), 18.05 (C, TBS), ꢀ4.24 (CH3, TBS), ꢀ4.79 (CH3
ꢂ2, TBS), ꢀ5.00 (CH3, TBS); HRESIMS m/z 467.2619 [MþNa]þ (calcd
for C22H44NaO5Si2 467.2619).
TBS); 13C NMR (100 MHz, CDCl3)
d 136.2 (C, NAP), 133.4 (C, NAP),
133.1 (C, NAP), 128.3 (CH, NAP), 127.9 (CH, NAP), 127.8 (CH, NAP),
126.3 (CH, NAP), 126.2 (CH, NAP), 126.0 (CH, NAP), 125.8 (CH, NAP),
81.74 (CH, C9), 78.55 (CH, C6), 76.93 (CH, C5), 72.66 (CH, C3), 70.60
(CH2, NAP), 66.94 (CH, C8), 66.44 (CH2, C1), 62.77 (CH2, C10), 40.79
(CH2, C7), 38.67 (CH2, C4), 36.55 (CH2, C2), 25.02 (CH3 ꢂ3, TBS),
18.01 (C, TBS), ꢀ4.09 (CH3, TBS), ꢀ4.81 (CH3, TBS); HRESIMS m/z
495.2534 [MþNa]þ (calcd for C27H40NaO5Si 495.2537).
4.1.4. NAP ether 18. To a suspension of LiAlH4 (175 mg, 4.62 mmol)
in Et2O (8 mL) was added a solution of 14 (585 mg, 1.32 mmol) in
Et2O (4 mL) at ꢀ30 ꢁC. After being stirred for 5 h at ꢀ30 to ꢀ20 ꢁC,
the reaction mixture was quenched with saturated aqueous
Roschell’s salt and stirred for 2 h. The mixture was extracted with
EtOAc and the organic layer was washed with brine. Concentration
and column chromatography (hexane/EtOAc 5:1e3:1) afforded
a mixture of alcohols 16 and 17 (592 mg, 1.32 mmol) in quantitative
yield.
4.1.6. Iodide 21. To a solution of 20 (3.20 g, 6.77 mmol) in THF were
added imidazole (740 mg,10.8 mmol), PPh3 (2.83 g,10.8 mmol), and
I2 (2.41 g, 9.48 mmol) at 0 ꢁC. After being stirred for 1 h at room
temperature, the mixture was quenched with saturated aqueous
NH4Cl and extracted with hexane/EtOAc (4:1). The organic layer
was washed with brine and dried over Na2SO4. Concentration and
purification by column chromatography (hexane/EtOAc 80:1e10:1)
To a solution of alcohols 16 and 17 in THF (3.3 mL) and DMF
(1.1 mL) was added NaH (60% in oil, 158 mg, 3.96 mmol) at 0 ꢁC.
After being stirred for 30 min, the mixture were added NAPBr
(583 mg, 2.64 mmol) and TBAI (97.5 mg, 264 mmol) at room tem-
perature. After being stirred for 15 h at room temperature, the re-
action mixture was quenched with saturated aqueous NH4Cl and
extracted with EtOAc. The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
chromatography (hexane/EtOAc 1:0e30:1) gave NAP ether 18
gave iodide 21 (3.88 g, 6.66 mmol) in 98% yield: colorless amor-
23
phous; [
a
]
þ22.3 (c 1.01, CHCl3); IR (film)
n
2950, 2927, 2856,
1H NMR (400 MHz,
7.85e7.79 (4H, m, NAP), 7.50e7.46 (3H, m, NAP), 4.76 (1H,
D
1470, 1360, 1252, 1096, 854, 837, 776 cmꢀ1
CDCl3)
;
d
d, J¼12.2 Hz, NAP), 4.68 (1H, d, J¼12.2 Hz, NAP), 3.97 (1H, ddd,
J¼12.9, 6.0, 3.9 Hz, H1), 3.90 (1H, dddd, J¼8.8, 6.8, 5.4, 3.3 Hz, H3),
3.61 (1H, ddd, J¼9.4, 9.4, 3.5 Hz, H5), 3.52 (1H, ddd, J¼12.9, 9.0,
3.1 Hz, H1), 3.47 (1H, dd, J¼10.5, 2.7 Hz, H10), 3.46 (1H, ddd, J¼11.3,
8.4, 4.5 Hz, H8), 3.28 (1H, dd, J¼10.5, 5.7 Hz, H10), 3.19 (1H, ddd,
J¼11.3, 9.4, 4.5 Hz, H6), 2.84 (1H, ddd, J¼8.4, 5.6, 2.7 Hz, H9), 2.43
(1H, J¼14.8, 5.4, 3.5 Hz, H4), 2.27 (1H, ddd, J¼11.3, 4.5, 4.5 Hz, H7),
2.10 (1H, dddd, J¼15.3, 8.8, 6.0, 3.1 Hz, H2), 1.96 (1H, dddd, J¼15.3,
9.0, 6.8, 3.9 Hz, H2), 1.90 (1H, ddd, J¼14.8, 9.4, 3.3 Hz, H4), 1.59 (1H,
ddd, J¼11.3, 11.3, 11.3 Hz, H7), 0.88 (9H, s, TBS), 0.12 (3H, s, TBS), 0.10
(515 mg, 877
(134 mg, 228
m
mol) in 65% yield along with the regioisomer 19
19
m
mol) in 17% yield. 18: colorless amorphous; [
2951, 2928, 2855, 1471, 1462, 1251,
1H NMR (400 MHz, CDCl3)
7.83e7.78
a]
D
þ29.7 (c 1.01, CHCl3); IR (film)
n
1095, 856, 836, 776 cmꢀ1
;
d
(4H, m, NAP), 4.49e7.44 (3H, m, NAP), 4.74 (1H, d, J¼12.3 Hz, NAP),
4.67 (1H, d, J¼12.3 Hz, NAP), 3.97 (1H, ddd, J¼12.9, 5.9, 3.9 Hz, H1),
3.87 (1H, dddd, J¼7.4, 5.9, 5.1, 3.5 Hz, H3), 3.82 (1H, dd, J¼11.3,
1.8 Hz, H10), 3.69 (1H, dd, J¼11.3, 4.7 Hz, H10), 3.60 (1H, ddd, J¼11.9,
9.2, 4.9 Hz, H8), 3.52 (1H, ddd, J¼12.9, 9.4, 2.9 Hz, H1), 3.50 (1H,
ddd, J¼9.2, 9.2, 3.4 Hz, H5), 3.12 (1H, ddd, J¼11.9, 9.2, 4.9 Hz, H6),
3.08 (1H, ddd, J¼9.2, 4.7, 1.8 Hz, H9), 2.39 (1H, ddd, J¼14.7, 5.1,
3.7 Hz, H4), 2.25 (1H, ddd, J¼11.9, 4.9, 4.9 Hz, H7), 2.11 (1H, dddd,
J¼15.0, 5.9, 5.9, 2.9 Hz, H2), 1.97 (1H, dddd, J¼15.0, 9.4, 7.4, 3.9 Hz,
H2),1.91 (1H, ddd, J¼14.7, 9.2, 3.5 Hz, H4),1.53 (1H, ddd, J¼11.9,11.9,
11.9 Hz, H7), 0.89 (9H, s, TBS), 0.87 (9H, s, TBS), 0.06 (6H, s, TBS),
(3H, s, TBS); 13C NMR (100 MHz, CDCl3)
d 136.2 (C, NAP), 133.4 (C,
NAP), 133.1 (C, NAP), 128.3 (CH, NAP), 128.0 (CH, NAP), 127.8
(CH, NAP), 126.4 (CH, NAP), 126.2 (CH, NAP), 126.0 (CH, NAP), 125.9
(CH, NAP), 79.88 (CH, C9), 78.43 (CH, C6), 77.11 (CH, C5), 72.55 (CH,
C3), 70.52 (CH2, NAP), 70.39 (CH, C8), 66.38 (CH2, C1), 40.45 (CH2,
C7), 38.23 (CH2, C4), 36.60 (CH2, C2), 25.87 (CH3 ꢂ3, TBS), 17.97 (C,
TBS), 8.76 (CH2, C10), ꢀ3.87 (CH3, TBS), ꢀ4.37 (CH3, TBS); HRESIMS
m/z 605.1558 [MþNa]þ (calcd for C27H39INaO4Si 605.1555).
0.05 (6H, s, TBS); 13C NMR (100 MHz, CDCl3)
d 136.3 (C, NAP), 133.4
(C, NAP), 133.1 (C, NAP), 128.3 (CH, NAP), 128.0 (CH, NAP), 127.8 (CH,
NAP), 126.3 (CH, NAP), 126.2 (CH, NAP), 125.9 (CH, NAP), 125.8 (CH,
NAP), 82.74 (CH, C9), 78.75 (CH, C6), 76.71 (CH, C5), 72.96 (CH, C3),
70.49 (CH2, NAP), 66.58 (CH2, C1), 66.08 (CH, C8), 62.89 (CH2, C10),
40.56 (CH2, C7), 38.64 (CH2, C4), 37.02 (CH2, C2), 26.11 (CH3 ꢂ3,
TBS), 25.89 (CH3 ꢂ3, TBS), 18.62 (C, TBS), 18.06 (C, TBS), ꢀ4.21 (CH3,
TBS), ꢀ4.70 (CH3, TBS), ꢀ4.78 (CH3, TBS), ꢀ4.96 (CH3, TBS); HRE-
SIMS m/z 609.3402 [MþNa]þ (calcd for C33H54NaO5Si2 609.3402).
4.1.7. Nitrile 22. To a solution of iodide 21 (4.18 g, 7.17 mmol) in
DMSO (14 mL) was added NaCN (703 mg, 14.3 mmol) at room
temperature. After being stirred for 20 h at 45 ꢁC, the mixture was
treated with saturated aqueous NaHCO3 and extracted with hex-
ane/EtOAc (4:1). The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
chromatography (hexane/EtOAc 1:0e10:1) gave nitrile 22 (3.40 g,
30
4.1.5. Alcohol 20. To a solution of 18 (3.27 g, 5.57 mmol) in MeOH
7.06 mmol) in 98% yield: colorless amorphous; [
CH2Cl2); IR (film)
839, 778 cmꢀ1; 1H NMR (400 MHz, CDCl3)
a]
þ12.9 (c 0.68,
D
(34 mL) and THF (34 mL) was added CSA (77 mg, 334
m
mol) at 0 ꢁC.
n
3056, 2952, 2931, 2858, 1737, 1509, 1467, 1098,
7.85e7.78 (4H, m, NAP),
After being stirred for 6 h at the same temperature, the mixture was
quenched with saturated aqueous NaHCO3 and extracted with
EtOAc. The organic layer was washed with brine and dried over
Na2SO4. Concentration and purification by column chromatography
d
7.51e7.45 (3H, m, NAP), 4.75 (1H, d, J¼12.3 Hz, NAP), 4.69 (1H, d,
J¼12.3 Hz, NAP), 3.98 (1H, ddd, J¼12.7, 6.0, 3.9 Hz, H1), 3.90 (1H, m,
H3), 3.58e3.52 (2H, m, H1, H5), 3.50 (1H, ddd, J¼12.1, 9.0, 4.5 Hz,
H8), 3.28 (1H, ddd, J¼9.0, 5.7, 3.5 Hz, H9), 3.20 (1H, ddd, J¼12.1, 9.2
4.3 Hz, H6), 2.70 (1H, dd, J¼16.6, 3.5 Hz, H10), 2.55 (1H, dd, J¼16.6,
5.7 Hz, H10), 2.40 (1H, ddd, J¼14.7, 4.6, 3.7 Hz, H4), 2.31 (1H, ddd,
(henxane/EtOAc 30:1e3:1) afforded alcohol 20 (2.49 g, 5.26 mmol)
19
in 95% yield: colorless amorphous; [
(film)
a]
þ36.3 (c 1.00, CHCl3); IR
D
n
3474, 2950, 2928, 2856, 1471, 1462, 1360, 1252, 1095, 857,

S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
6621
J¼12.1, 4.5, 4.5 Hz, H7), 2.10 (1H, dddd, J¼15.5, 8.8, 6.0, 2.9 Hz, H2),
1.98 (1H, dddd, J¼15.5, 8.8, 7.1, 3.9 Hz, H2),1.89 (1H, ddd, J¼14.7, 9.4,
3.3 Hz, H4), 1.54 (1H, ddd, J¼12.1, 12.1, 12.1 Hz, H7), 0.87 (9H, s, TBS),
37.6 (CH2, C10), 36.6 (CH2, C2), 25.8 (TBS),18.0 (TBS), ꢀ3.9 (TBS), ꢀ4.7
(TBS); HRESIMS m/z 523.2494 [MþNa]þ (calcd for C28H40NaO6Si
523.2490).
0.11 (3H, s, TBS), 0.10 (3H, s, TBS); 13C NMR (100 MHz, CDCl3)
d 136.3
(C, NAP), 133.5 (C, NAP), 133.2 (C, NAP), 128.5 (CH, NAP), 128.1 (CH,
NAP), 128.0 (CH, NAP), 126.5 (CH, NAP), 126.4 (CH, NAP), 126.1 (CH,
NAP), 126.0 (CH, NAP), 117.6 (C, C11), 78.17 (CH, C6), 77.66 (CH, C5),
77.16 (CH, C9), 72.62 (CH, C3), 70.52 (CH2, NAP), 69.43 (CH, C8),
66.63 (CH2, C1), 40.61 (CH2, C1), 38.44 (CH2, C1), 36.54 (CH2, C2),
25.94 (CH3 ꢂ3, TBS), 21.25 (CH2, C10), 18.09 (C, TBS), ꢀ3.78 (CH3,
TBS), ꢀ4.59 (CH3, TBS); HRESIMS m/z 504.2543 [MþNa]þ (calcd for
C28H39NNaO4Si 504.2541).
4.1.10. TES ether 24. To a solution of carboxylic acid 7 (415 mg,
829 mmol) in THF (16.5 mL) was added TBAF (1.0 M in THF, 1.7 mL,
1.7 mmol) at room temperature. After being stirred for 4 h at 45 ꢁC,
the mixture was quenched with saturated aqueous NH4Cl and
extracted with EtOAc. The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
chromatography (hexane/EtOAc 3:1e0:1) gave the corresponding
alcohol S1 (228 mg, 745
m
mol) in 90% yield: colorless amorphous;
þ9.2 (c 1.01, CHCl3); IR (film) 3423, 2938, 2870, 1712, 1352,
1272,1192,1123,1069 cmꢀ1; 1H NMR (400 MHz, CD3OD)
7.91e7.81
25
[a
]
n
D
4.1.8. Aldehyde 23. To a solution of 22 (3.40 g, 7.06 mmol) in CH2Cl2
(70 mL) was added DIBAL (1.0 M in hexane, 21 mL, 21 mmol) at
ꢀ80 ꢁC. After being stirred for 1 h at the same temperature, EtOAc
(15 mL) and saturated aqueous Rochell’s salt were added and
extracted with EtOAc. The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
d
(4H, m, NAP), 7.51e7.45 (3H, m, NAP), 4.41 (1H, d, J¼12.0 Hz, NAP),
4.67 (1H, d, J¼12.0 Hz, NAP), 3.93 (1H, ddd, J¼12.7, 5.9, 3.9 Hz, H1),
3.76 (1H, dddd, J¼6.9, 5.9, 5.1, 3.3 Hz, H3), 3.57 (1H, ddd, J¼12.7, 8.4,
3.3 Hz, H1), 3.53 (1H, ddd, J¼9.4, 9.4, 2.7 Hz, H9), 3.50 (1H, ddd, J¼9.4,
9.2, 3.9 Hz, H5), 3.31 (1H, ddd, J¼11.5, 9.4, 4.7 Hz, H8), 3.21 (1H, ddd,
J¼11.5, 9.2, 4.7 Hz, H6), 2.87 (1H, dd, J¼16.0, 2.7 Hz, H10), 2.36 (1H,
ddd, J¼14.7, 5.1, 3.9 Hz, H4), 2.34 (1H, ddd, J¼11.5, 4.7, 4.7 Hz, H7),
2.31 (1H, dd, J¼16.0, 9.4 Hz, H10), 2.12 (1H, dddd, J¼15.0, 5.9, 5.9,
3.3 Hz, H2),1.94 (1H, dddd, J¼15.0, 8.4, 6.9, 3.9 Hz, H2),1.89 (1H, ddd,
J¼14.7, 9.4, 3.3 Hz, H4), 1.52 (1H, ddd, J¼11.5, 11.5, 11.5 Hz, H7); 13C
chromatography (hexane/EtOAc 30:1e3:1) gave aldehyde 23
29
(3.27 g, 6.79 mmol) in 96% yield: Colorless amorphous; [
(c 1.00, CHCl3); IR (film)
1096 cmꢀ1; 1H NMR (400 MHz, CDCl3)
a
]
D
þ30.2
n
2928, 2856, 1727, 1461, 1361, 1252,
9.75 (1H, s, CHO), 7.78e7.85
d
(1H, m, NAP), 7.45e7.5 (1H, m, NAP), 4.72 (1H, d, J¼12.4 Hz, NAP),
4.66 (1H, d, J¼12.4 Hz, NAP), 3.97 (1H, ddd, J¼12.8, 6.0, 3.6 Hz, H1),
3.85e3.90 (1H, m, H3), 3.55e3.65 (2H, m, H5, H9), 3.51 (1H, ddd,
J¼12.8, 9.6, 3.2 Hz, H1), 3.41 (1H, ddd, J¼11.2, 8.8, 4.0 Hz, H8), 3.17
(1H, ddd, J¼11.2, 9.2, 4.0 Hz, H6), 2.73 (1H, dd, J¼15.2, 2.0 Hz, H10),
2.40 (1H, ddd, J¼14.8, 8.4, 3.6 Hz, H4), 2.28e2.39 (2H, m, H10, H7),
2.11 (1H, dddd, J¼14.8, 6.0, 6.0, 3.2 Hz, H2), 1.97 (1H, dddd, J¼14.8,
9.6, 7.2, 3.6 Hz, H2), 1.84 (1H, ddd, J¼14.8, 10.0, 3.2 Hz, H4), 1.58 (1H,
ddd, J¼11.2,11.2,11.2 Hz, H7), 0.087 (9H, s, TBS), 0.06 (6H, s, TBS); 13C
NMR (100 MHz, CD3OD)
d 175.6 (C, C11), 137.5 (C, NAP), 134.6 (C,
NAP), 134.3 (C, NAP), 129.0 (CH, NAP), 128.9 (CH, NAP), 128.6
(CH, NAP), 127.3 (CH, NAP), 127.1 (CH, NAP), 126.9 (CH, NAP), 126.8
(CH, NAP), 80.04 (CH, C9), 79.58 (CH, C6), 78.31 (CH, C5), 74.14 (CH,
C3), 71.28 (CH2, NAP), 69.80 (CH, C8), 67.21 (CH2, C1), 41.13 (CH2, C7),
39.19 (CH2, C4), 38.60 (CH2, C10), 37.26 (CH2, C2); HRESIMS m/z
409.1617 [MþNa]þ (calcd for C22H26NaO6 409.1622).
To a solution of the above alcohol S1 (228 mg, 745 mmol) in DMF
NMR (100 MHz, CDCl3)
d
201.6 (CHO),136.2 (NAP),133.4 (NAP),133.1
(6 mL) were added imidazole (305 mg, 4.48 mmol) and TESCl
(338 mg, 2.24 mmol) at room temperature. After being stirred for 2 h
at room temperature, the mixture was treated with saturated aque-
ous NaHCO3 and extracted with EtOAc. The aqueous layer was added
solid NH4Cl and extracted with EtOAc. The combined organic layer
was washed with brine and dried over Na2SO4. Concentration and
purification by column chromatography (hexane/EtOAc 10:1e1:1)
(NAP), 128.3 (NAP), 128.0 (NAP), 127.8 (NAP), 126.4 (NAP), 126.3
(NAP),126.0 (NAP),125.8 (NAP), 78.5 (CH, C8), 77.6 (CH, C5), 77.3 (CH,
C9), 72.6 (CH, C3), 70.6 (CH2, NAP), 70.5 (CH, C6), 66.5 (CH2, C1), 46.4
(CH2, C10), 40.9 (CH2, C7), 38.5 (CH2, C4), 36.6 (CH2, C2), 25.9 (TBS),
18.0 (TBS), ꢀ3.9 (TBS), ꢀ4.6 (TBS); HRESIMS m/z 507.2534 [MþNa]þ
(calcd for C28H40NaO5Si 507.2543).
gave TES ether 24 (342 mg, 683
m
mol) in 92% yield: colorless amor-
þ20.9 (c 1.01, CHCl3); IR (film) 2953, 2875,1714, 1456,
1H NMR (400 MHz, CDCl3)
7.70e7.65 (4H, m, NAP), 7.39e7.33 (3H, m, NAP), 4.60 (1H, d,
25
4.1.9. Carboxylic acid 7. To a mixture of aldehyde 23 (980 mg,
2.03 mmol), NaH2PO4$2H2O (550 mg, 4.58 mmol), and 2-methyl-2-
butene (1.7 mL, 16.2 mmol) in t-BuOH (8 mL) and H2O (2 mL) was
added NaClO2 (550 mg, 6.09 mmol) at room temperature. After being
stirred for 3 h at room temperature, the mixture was treated with
saturatedaqueousNa2S2O3 andNH4Cl, andextractedwithEtOAc. The
organic layer was washed with brine and dried over Na2SO4. Con-
centration and purification by column chromatography (hexane/
phous; [
a
]
n
D
1238, 1094, 1006, 821, 745 cmꢀ1
;
d
J¼12.3 Hz, NAP), 4.52 (1H, d, J¼12.3 Hz, NAP), 3.86 (1H, ddd, J¼12.7,
5.7, 3.7 Hz, H1), 3.74 (1H, dddd, J¼8.8, 5.7, 4.9, 3.3 Hz, H3), 3.50 (1H,
ddd, J¼9.4, 9.2, 4.9 Hz, H5), 3.45 (1H, ddd, J¼9.2, 8.8, 3.3 Hz, H9), 3.42
(1H, ddd, J¼12.7, 7.2, 3.1 Hz, H1), 3.33(1H, ddd, J¼11.4, 9.2, 4.5 Hz,H8),
3.07 (1H, ddd, J¼11.4, 9.2, 4.5 Hz, H6), 2.75 (1H, dd, J¼15.7, 3.3 Hz,
H10), 2.30 (1H, dd, J¼15.7, 8.8 Hz, H10), 2.27 (1H, ddd, J¼14.6, 4.9,
4.9 Hz, H4), 2.19 (1H, ddd, J¼11.4, 4.5, 4.5 Hz, H7), 1.99 (1H, dddd,
J¼15.3, 5.7, 5.7, 3.1 Hz, H2),1.84 (1H, dddd, J¼15.3, 8.8, 7.2, 3.7 Hz, H2),
1.73 (1H, ddd, J¼14.6, 9.4, 3.3 Hz, H4), 1.46 (1H, ddd, J¼11.4, 11.4,
11.4 Hz, H7), 0.84 (9H, t, J¼8.0 Hz, TES), 0.49 (6H, q, J¼8.0 Hz, TES); 13C
EtOAc 10:1e3:1) gave carboxylic acid 7 (920 mg, 1.83 mmol) in 90%
29
D
yield: colorless solid; mp 102 ꢁC; [
n
a]
þ34.2 (c 1.00, CHCl3); IR (film)
2929, 2857, 1713, 1462, 1360, 1254, 1095 cmꢀ1; 1H NMR (400 MHz,
CDCl3) d 7.80e7.77 (4H, m, NAP), 7.48e7.46 (3H, m, NAP), 4.72 (1H, d,
J¼12.4 Hz, NAP), 4.66 (1H, d, J¼12.4 Hz, NAP), 3.97 (1H, ddd, J¼12.8,
6.0, 4.0 Hz, H1), 3.85 (1H, m, H3), 3.57 (1H, ddd, J¼14.4, 8.8, 3.6 Hz,
H9), 3.54 (1H, m, H5), 3.51 (1H, ddd, J¼12.8, 8.4, 3.2 Hz, H1), 3.42 (1H,
ddd, J¼11.6, 8.8, 4.4Hz, H8), 3.18 (1H, ddd, J¼11.6, 9.2, 4.4 Hz, H6), 2.83
(1H, dd, J¼15.6, 3.6 Hz, H10), 2.39 (1H, dd, J¼15.6,14.4 Hz, H10), 2.38
(1H, ddd, J¼14.4, 4.0, 4.0 Hz, H4), 2.29 (1H, ddd, J¼11.6, 4.4, 4.4 Hz,
H7), 2.07 (1H, dddd, J¼15.2, 11.6, 6.0, 3.2 Hz, H2), 1.95 (1H, dddd,
J¼15.2, 8.4, 5.6, 4.0 Hz, H2),1.84 (1H, ddd, J¼14.4, 9.6, 3.2 Hz, H4),1.57
(1H, ddd, J¼11.6,11.6,11.6 Hz, H7),1.26 (1H, t, J¼7.2 Hz, OH), 0.87 (9H,
NMR (100 MHz, CDCl3) d 176.8 (CO2H),136.1 (NAP),133.4 (NAP),133.1
(NAP),128.3(NAP),128.0(NAP),127.8(NAP),126.5(NAP),126.2(NAP),
125.9 (NAP), 78.6 (CH, C9), 78.3 (CH, C6), 77.2 (CH, C5), 72.5 (CH, C3),
70.5 (CH2, NAP), 70.1 (CH, C8), 66.4(CH2, C1), 40.9(CH2,C7), 38.3(CH2,
C4), 36.5 (CH2, C10), 36.5 (CH2, C2), 6.92 (CH2, TES), 5.13 (CH3, TES);
HRESIMS m/z 523.2485 [MþNa]þ (calcd for C28H40NaO6Si 523.2486).
4.1.11. Ester 25b. To a mixture of carboxylic acid 24 (1.75 g,
3.50 mmol) and alcohol 8 (1.48 g, 2.57 mmol) were added Et3N
(2.2 mL, 15.4 mmol) and 2,4,6-trichlorobenzoyl chloride (1.6 mL,
10.3 mmol) at room temperature. After being stirred for 30 min,
the mixture was added DMAP (3.14 g, 25.7 mmol) and stirred for
additional 1 h. The reaction mixture was quenched with H2O and
s, TBS), 0.07 (6H, d, J¼4.0 Hz, TBS); 13C NMR (100 MHz, CDCl3)
d 176.7
(CO2H), 136.1 (NAP), 133.4 (NAP), 133.1 (NAP), 128.3 (NAP), 128.0
(NAP), 127.8 (NAP), 126.5 (NAP), 126.2 (NAP), 125.93 (NAP), 125.91
(NAP), 78.6 (CH, C9), 78.3 (CH, C6), 77.3 (CH, C5), 72.6 (CH, C3), 70.5
(CH2, NAP), 70.1 (CH, C8), 66.4(CH2, C1), 40.8 (CH2, C7), 38.4 (CH2, C4),

6622
S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
extracted with EtOAc. The organic layer was washed with brine and
dried over Na2SO4. Concentration and purification by column
3.3 mL, 3.3 mmol), and the mixture was stirred for 1 h at room
temperature. To a solution of acetal 26b (1.84 g, 1.67 mmol) in
CH2Cl2 (53 mL) at 0 ꢁC was added freshly prepared i-Bu2AlSePh.
After being stirred for 1 h at 0 ꢁC, the mixture was quenched with
EtOAc and saturated aqueous Rochell’s salt. After being stirred for
1 h, the mixture was extracted with EtOAc, and the organic layer
was washed with brine and dried over Na2SO4. Concentration and
purification by flash column chromatography (hexane/EtOAc
20:1e1:1) gave O,Se-acetal 27b (1.71 g, 1.43 mmol) in 86% yield:
chromatography (hexane/EtOAc 10:1e1:1) afforded ester 25b
25
(2.56 g, 2.42 mmol) in 94% yield: colorless amorphous; [
(c 1.03, CHCl3); IR (film)
1H NMR (400 MHz, C6D6)
a]
ꢀ31.5
D
n
2930, 2856, 1740, 1518, 1250, 1105 cmꢀ1
7.84e7.60 (8H, m, MP, NAP, TBDPS),
;
d
7.49e7.34 (11H, m, MP, NAP, TBDPS), 6.91 (2H, d, J¼8.8 Hz), 5.99
(1H, dd, J¼11.0, 5.0 Hz, H19), 5.74 (1H, ddd, J¼11.0, 10.3, 6.5 Hz,
H18), 5.39 (1H, s, MP), 4.87 (1H, ddd, J¼9.6, 2.9, 2.9 Hz, H16), 4.25
(1H, m, H20), 4.00 (1H, ddd, J¼12.5, 5.9, 3.7 Hz, H1), 3.89e3.82 (3H,
m, H3, H15, H22), 3.81 (3H, s, MP), 3.69 (1H, ddd, J¼10.3, 7.0, 3.5 Hz,
H130), 3.62 (1H, ddd, J¼10.3, 10.3, 4.9 Hz, H130), 3.58e3.43 (5H, m,
H1, H5, H8, H9, H22), 3.35 (1H, ddd, J¼14.3, 14.3, 5.1 Hz, H21), 3.18
(1H, ddd, J¼11.4, 9.2, 4.3 Hz, H6), 2.76 (1H, dd, J¼14.3, 3.1 Hz, H10),
2.69 (1H, ddd, J¼13.7, 10.3, 2.9 Hz, H17), 2.46 (1H, ddd, J¼13.7, 6.5,
2.9 Hz, H17), 2.34e2.28 (3H, m, H4, H7, H10), 2.10 (1H, dddd, J¼15.1,
5.9, 5.9, 2.8 Hz, H2), 1.95e1.78 (3H, m, H2, H4, H14), 1.59 (1H, ddd,
J¼11.4, 11.4, 11.4 Hz, H7), 1.40 (1H, m, H14), 1.11 (9H, s, TBDPS), 0.96
(9H, t, J¼8.0 Hz, TES), 0.62 (6H, q, J¼8.0 Hz, TES); 13C NMR
colorless amorphous; IR (film)
n
3069, 3062, 2953, 2874, 1737, 1615,
7.94e7.04
1518, 1101, 823, 738 cmꢀ1 1H NMR (400 MHz, C6D6)
;
d
(24H, m, NAP, TBDPS, MP, Ph), 6.95 (1H, d, J¼8.8 Hz, MP), 6.92 (1H,
d, J¼8.8 Hz, MP), 6.17e6.15 (1H, m, H11, H18), 6.13 (1/2H, dd, J¼11.0,
4.9 Hz), 5.84e5.77 (3/2H, m, H11, H18), 5.38 (1/2H, s, MP), 5.36 (1/
2H, s, MP), 4.64 (1/2H, d, J¼12.4 Hz, NAP), 4.60 (1/2H, d, J¼12.4 Hz,
NAP), 4.50 (1H, s, NAP), 4.39e4.33 (1H, m, H20), 4.22 (1/2H, m,
H16), 4.20 (1/2H, dd, J¼10.4, 4.7 Hz, H22), 4.12 (1/2H, ddd, J¼10.1,
10.1,1.5 Hz, H15), 4.04 (1/2H, ddd, J¼9.4, 9.4,1.6 Hz, H15), 4.00e3.58
(15/2H, m, H1, H3, H5, H8, H9, H130 ꢂ2, H16, H21), 3.53 (1/2H, dd,
J¼10.4, 10.4 Hz, H22), 3.46e3.41 (2H, m, H8, H17, H21, H22), 3.39 (3/
2H, s, MP), 3.36 (3/2H, s, MP), 3.33e3.17 (2H, m, H1, H6), 2.98e2.88
(1H, m, H10), 2.81 (1/2H, m, H17), 2.65e2.47 (7/2H, m, H4, H7, H14,
H17), 2.38 (1/2H, ddd, J¼13.9, 9.4, 3.9 Hz, H10), 2.30e2.17 (1H, m,
H10, H14), 2.10e1.87 (4H, m, H2 ꢂ2, H4, H7), 1.77 (1/2H, m, H14),
1.56 (1/2H, m, H14), 1.33 (9/2H, s, TBDPS), 1.29 (9/2H, s, TBDPS), 1.04
(3/2H, t, J¼7.9 Hz, TES), 0.96 (3/2H, t, J¼7.9 Hz, TES), 0.63 (1H, q,
J¼7.9 Hz, TES), 0.50 (1H, q, J¼7.9 Hz, TES); HRESIMS m/z 1221.4817
[MþNa]þ (calcd for C68H86NaO10SeSi2 1221.4819).
(100 MHz, CDCl3) d 171.2 (C, C11),160.2 (C, MP),136.1 (C, NAP),135.7
(CH ꢂ4, TBDPS),134.2 (CH, C19),133.7 (C ꢂ2, TBDPS),133.3 (C, NAP),
133.1 (C, NAP), 130.3 (C, MP), 129.9e129.8 (CH ꢂ2, MP, NAP),
128.3e126.4 (CH ꢂ9, TBDPS ꢂ6, NAP ꢂ3), 126.2 (CH, C18), 125.94
(CH, NAP), 125.91 (CH, NAP), 125.8 (CH, NAP), 113.8 (CH, MP), 100.9
(CH, MP), 79.77 (CH, C20), 79.43 (CH, C9), 78.49 (CH, C6), 77.23
(CH, C8), 77.06 (CH, C16), 76.06 (CH, C15), 75.84 (CH, C21), 72.66
(CH, C3), 70.50 (CH2, NAP), 70.20 (CH, C5), 69.29 (CH2, C22),
66.67 (CH2, C1), 59.86 (CH2, 130), 55.42 (CH3, MP), 40.98 (CH2,
C7), 38.66 (CH2, C4), 38.28 (CH2, C10), 36.68 (CH2, C2), 36.13 (CH2,
C14), 29.90 (CH2, C17), 27.09 (CH3 ꢂ6, TBDPS), 19.29 (C ꢂ2, TBDPS),
6.98 (CH3 ꢂ3, TES), 5.12 (CH2 ꢂ3, TES); HRESIMS m/z 1123.5392
[MþNa]þ (calcd for C64H84NaO12Si2 1123.5394).
4.1.14. Alcohol 29. To a solution of O,Se-acetal 27b (40.5 mg,
33.8
135
m
mol) in THF (1.7 mL) at ꢀ45 ꢁC was added TBAF (1.0 M in THF,
mL, 135
m
mol). After being stirred for 3 h at ꢀ30 ꢁC, the mixture
was added TBAF (65 mL, 65 mmol) and stirred for additional 3 h. The
4.1.12. Acetate 26b. To a solution of ester 25b (635 mg, 601
m
mol) in
mixture was quenched with saturated aqueous NH4Cl, extracted
with EtOAc. The organic layer was washed with brine and dried
over Na2SO4. Concentration and purification by flash column
chromatography (hexane/EtOAc 20:1e1:1) gave alcohol 29
CH2Cl2 (10 mL) was added DIBAL (1.0 M in hexane, 900 L, 900
m
m
mol)
at ꢀ90 ꢁC. After being stirred for 1 h at the same temperature,
a mixture of Ac2O (142 mL,1.5 mmol) and DMAP (293 mg, 2.4 mmol)
in CH2Cl2 was added. The reaction mixture was allowed to warm up
to 0 ꢁC over 2 h. The mixture was quenched with saturated aqueous
Rochell’s salt and extracted with EtOAc. The organic layer was
washed with brine and dried over Na2SO4. Concentration and pu-
rification by column chromatography (hexane/EtOAc 15:1e2:1)
(34.9 mg, 32.2
3462, 3050, 2929, 2856, 1734, 1615, 1249, 1103, 822, 738 cmꢀ1
NMR (400 MHz, C6D6)
m
mol) in 95% yield: colorless amorphous; IR (film)
n
;
1H
d
7.85e6.90 (24H, m, NAP, MP, TBDPS, Ph),
6.84 (1H, d, J¼9.0 Hz, MP), 6.82 (1H, d, J¼9.0 Hz, MP), 6.11e6.04 (1H,
m, H18, H19), 6.02 (1/2H, dd, J¼11.0, 4.7 Hz, H19), 5.66 (1/2H, dd,
J¼8.2, 4.3 Hz, H11), 5.64 (1/2H, m, H18), 5.62 (1/2H, dd, J¼10.6,
2.6 Hz, H11), 5.27 (1/2H, s, MP), 5.25 (1/2H, s, MP), 4.49 (1/2H, d,
J¼12.7 Hz, NAP), 4.46 (1/2H, d, J¼12.7 Hz, NAP), 4.36 (1H, s, NAP),
4.27 (1/2H, dd, J¼9.0, 3.9 Hz, H20), 4.22 (1/2H, dd, J¼6.9, 5.5 Hz,
H20), 4.14e4.02 (3/2H, m, H15, H16, H22), 3.92 (1/2H, m, H15),
3.84e3.77 (3/2H, m, H1, H130), 3.74 (1/2H, dd, J¼10.4, 4.8 Hz, H22),
3.71e3.62 (3/2H, m, H5, H16), 3.57e3.30 (9/2H, m, H3, H9, H130,
H21, H22), 3.28 (3/2H, s, MP), 3.26 (3/2H, s, MP), 3.24e3.22 (1H, m,
H8, H17), 3.17e3.09 (1H, m, H1), 3.06e2.83 (2H, m, H6, H8, H10),
2.72e2.64 (1H, m, H10, H17), 2.52e2.35 (2H, m, H4, H14, H17), 2.26
(1/2H, ddd, J¼11.6, 4.3, 4.3 Hz, H7), 2.23e2.09 (5/2H, m, H7, H10,
H14, H17), 1.92e1.65 (7/2H, m, H2 ꢂ2, H4, H14), 1.57 (1/2H, ddd,
J¼11.7, 11.7, 11.7 Hz, H7), 1.49 (1/2H, ddd, J¼11.6, 11.6, 11.6 Hz, H7),
1.42 (1/2H, m, H14); HRESIMS m/z 1107.3953 [MþNa]þ (calcd for
C62H72NaO10SeSi 1107.3952).
gave acetate 26b (613 mg, 557
phous; IR (film) 2954, 2875, 1736, 1615, 1518, 1248, 1110, 823, 744,
703 cmꢀ1 1H NMR (400 MHz, C6D6)
8.00e7.35 (19H, m, NAP,
mmol) in 93% yield: colorless amor-
n
;
d
TBDPS, MP), 6.95 (3/4H, d, J¼8.4 Hz, MP), 6.93 (5/4H, d, J¼8.8 Hz,
MP), 6.82 (5/8H, dd, J¼10.6, 3.4 Hz, H11), 6.75 (3/8H, dd, J¼8.8, 2.4 Hz,
H11), 6.16 (3/8H, dd, J¼11.1, 4.9 Hz, H19), 6.11 (5/8H, dd, J¼11.0,
4.9 Hz, H19), 6.05 (3/8H, m, H18), 5.84 (5/8H, m, H18), 5.39 (3/8H, s,
MP), 5.35 (5/8H, s, MP), 4.84 (5/8H, d, J¼12.2 Hz, NAP), 4.61 (5/8H, d,
J¼12.2 Hz, NAP), 4.49 (3/8H, d, J¼12.5 Hz, NAP), 4.44 (3/8H, d,
J¼12.5 Hz, NAP), 4.40 (3/8H, m, H20), 4.32 (5/8H, m, H20), 4.16 (5/8H,
dd, J¼9.6, 3.9 Hz, H22), 4.12 (3/8H, m, H15), 4.03e3.85 (35/8H, m, H1,
H5, H130, H15, H16, H22), 3.81e3.77 (1H, m, H5, H9), 3.70e3.64 (13/
8H, m, H3, H8), 3.60e3.43 (29/8H, m, H8, H9, H130, H21, H22), 3.38
(9/8H, s, MP), 3.37 (15/8H, m, MP), 3.36e3.22 (19/8H, m, H1, H6,
H22), 2.82 (3/8H, m, H17), 2.79e2.48 (37/8H, m, H4, H7, H10, H14,
H17), 2.34 (3/8H, m, H14), 2.16 (5/8H, ddd, J¼13.3,10.6, 2.9 Hz, H10),
2.06e1.87 (35/8H, m, H2 ꢂ2, H4, H7, H10),1.82 (9/8H, s, Ac),1.75 (15/
8H, s, Ac), 1.60 (1H, m, H14), 1.37 (27/8H, s, TBDPS), 1.28 (45/8H, s,
TBDPS), 1.07 (15/8H, t, J¼8.0 Hz, TES), 1.03 (9/8H, t, J¼8.0 Hz, TES),
0.67 (5/4H, q, J¼8.0Hz, TES), 0.62 (3/4H, q, TES); HRESIMS m/z
1123.5392 [MþNa]þ (calcd for C64H84NaO12Si2 1123.5394).
4.1.15. Vinyl sulfoxide 6. To a solution of alcohol 29 (930 mg,
854 m
mol) in THF (65 mL) at 0 ꢁC was added NaH (60% in oil,102 mg,
2.56 mmol) and the mixture was warmed to room temperature.
After being stirred for 1 h, the reaction mixture was added a solu-
tion of sulfoxide 30 (210 mg, 1.28 mmol) and H2O (15 mL, 854 mmol)
in THF (0.5 mL). After being stirred for 40 min, the mixture was
quenched with saturated aqueous NH4Cl, extracted with EtOAc. The
organic layer was washed with brine and dried over Na2SO4.
4.1.13. O,Se-Acetal 27b. To
a solution of (PhSe)2 (677 mg,
2.17 mmol) in CH2Cl2 (30 mL) was added DIBAL (1.0 M in hexane,

S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
6623
Concentration and purification by flash column chromatography
(hexane/EtOAc 10:1e1:1) gave vinyl sulfoxide 6 (690 mg, 553 mol)
in 65% yield along with recovered 29 (278 mg, 256 mol) in 30%
yield. 6: colorless amorphous; IR (film) 2929, 2856, 1735, 1617,
1248, 1103, 1041, 822, 738, 704 cmꢀ1 1H NMR (400 MHz, C6D6)
7.85e6.82 (30H, m, NAP, MP, TBDPS, Ph, p-Tol), 6.08 (1/2H, dd,
1740, 1615, 1517, 1461, 1427, 1385, 1249, 1103, 823, 754, 703 cmꢀ1
1H NMR (400 MHz, C6D6)
9.47 (1H, s, H13), 7.85e7.24 (19H, m,
;
m
d
m
MP, NAP, TBDPS), 6.83 (2H, d, J¼9.2 Hz, MP), 6.04 (1H, dd, J¼10.9,
5.0 Hz, H19), 5.63 (1H, m, H18), 5.33 (1H, s, MP), 4.52 (1H, d,
J¼125 Hz, NAP), 4.49 (1H, d, J¼12.5 Hz, NAP), 4.31 (1H, m, H20),
4.10 (1H, dd, J¼10.1, 4.7 Hz, H22), 3.88e3.78 (4H, m, H1, H130 ꢂ2,
H15), 3.71 (1H, ddd, J¼9.8, 9.8, 2.5 Hz, H5), 3.57e3.49 (2H, m, H3,
H21), 3.45 (1H, dd, J¼10.1, 10.1 Hz, H22), 3.40e3.36 (2H, m, H12,
H16), 3.27 (3H, s, MP), 3.24e3.13 (2H, m, H1, H11), 3.04 (1H, ddd,
J¼11.3, 9.0, 4.5 Hz, H6), 2.78 (1H, ddd, J¼11.3, 9.2, 4.5 Hz, H8), 2.67
(1H, ddd, J¼11.5, 9.2, 4.0 Hz, H9), 2.58e2.50 (2H, m, H4, H17), 2.43
(1H, ddd, J¼11.3, 4.5, 4.5 Hz, H7), 2.26 (1H, ddd, J¼11.5, 4.0, 4.0 Hz,
H10), 2.21e2.16 (1H, m, H14), 2.12e2.06 (1H, m, H17), 1.95e1.88
(2H, m, H2 ꢂ2), 1.82e1.78 (1H, m, H4), 1.74 (1H, ddd, J¼11.3, 11.3,
11.3 Hz, H7), 1.54e1.47 (1H, m, H14), 1.46 (1H, ddd, J¼11.5, 11.5,
n
;
d
J¼11.1, 4.9 Hz, H19), 6.05e6.01 (1H, m, H18, H19), 5.87 (1/2H, d,
J¼5.7 Hz, H12), 5.80 (1/2H, m, H18), 5.68 (1/2H, m, H11), 5.64 (1/2H,
d, J¼5.5 Hz, H12), 5.59 (1/2H, m, H11), 5.30 (1/2H, d, J¼5.7 Hz, H13),
5.28 (1/2H, s, MP), 5.24 (1/2H, s, MP), 5.22 (1/2H, d, J¼5.5 Hz, H13),
4.52 (1/2H, d, J¼12.1 Hz, NAP), 4.48 (1/2H, d, J¼12.1 Hz, NAP), 4.39
(1H, s, NAP), 4.25e4.22 (1H, m, H20), 4.16 (1/2H, m, H16), 4.12e4.04
(2H, m, H130, H16, H22), 4.01 (1/2H, m, H15), 3.96 (1/2H, m, H15),
3.86e3.61 (11/2H, m, H1, H5, H6, H9, H130, H21, H22), 3.58e3.53
(1H, m, H3), 3.45e3.34 (3/2H, m, H8, H17, H22), 3.29e3.22 (1H, m,
H21, H22), 3.27 (3/2H, s, MP), 3.25 (3/2H, s, MP), ; 3.18e3.07 (3/2H,
m, H1, H8), 3.04e2.96 (1H, m, H6), 2.88 (1/2H, m, H10), 2.71e2.60
(1H, m, H10, H17), 2.52e2.34 (3H, m, H4, H14, H17 ꢂ2), 2.31e2.19
(3/2H, m, H7, H10), 2.12 (1/2H, m, H10), 1.96 (3/2H, s, p-Tol), 1.94 (3/
2H, m, p-Tol), 1.88e1.66 (9/2H, m, H2 ꢂ2, H4, H7, H14), 1.25 (1/2H,
m, H14), 1.20 (9/2H, s, TBDPS), 1.14 (9/2H, s, TBDPS); HRESIMS m/z
1271.4247 [MþNa]þ (calcd for C71H80NaO11SSeSi 1271.4248).
11.5 Hz, H10); 13C NMR (100 MHz, C6D6)
d 196.7 (CH, C13), 160.3
(C, MP), 136.6e135.8 (ꢂ2, NAP, TBDPS), 134.0 (CH, C19),
133.8e126.2 (22C, MP, NAP, TBDPS), 126.0 (CH, C18), 125.9 (CH,
NAP), 125.7 (CH, NAP), 113.6 (CH, MP), 100.9 (CH, MP), 83.78 (CH,
C16), 83.08 (CH, C12), 80.00 (CH, C20), 79.29 (CH, C6), 77.50
(CH, C5), 77.40 (CH, C15), 76.20 (CH, C8), 76.00 (CH, C21), 74.99
(CH, C9), 72.75 (CH, C3), 72.27 (CH, C11), 70.38 (CH2, NAP), 69.44
(CH2, C22), 66.13 (CH2, C1), 60.38 (CH2, C130), 54.58 (CH3, MP),
38.84 (CH2, C4), 37.49 (CH2, C10), 36.93 (CH2, C7), 36.49 (CH2, C14),
36.46 (CH2, C2), 30.41 (CH2, C17), 26.97 (CH3 ꢂ3, TBDPS), 19.17 (C,
TBDPS); HRESIMS m/z 991.4417 [MþNa]þ (calcd for C58H68NaO11Si
991.4423).
4.1.16. Sulfoxide 31. To a mixture of 6 (387 mg, 310
mmol) and
n-Bu3SnH (750
m
L, 2.79 mmol) in toluene (103 mL) at ꢀ78 ꢁC was
added Et3B (1.0 M in THF, 2.5 mL, 2.5 mmol). After being stirred for
3 h at ꢀ40 ꢁC, the reaction mixture was concentrated and directly
subjected to flash column chromatography (hexane/EtOAc 4:1e1:3)
To
a suspension of methyltriphenylphosphonium bromide
to give sulfoxide 31 (236 mg, 216
m
mol) in 70% yield: colorless
ꢀ60.4 (c 1.01, CHCl3); IR (film) 2930, 2856,1616,
1517, 1459, 1427, 1387, 1249, 1104, 1038, 823, 754, 703 cmꢀ1 1H
NMR (400 MHz, C6D6) 7.82e7.21 (21H, m, MP, NAP, TBDPS, p-Tol),
(579 mg, 1.62 mmol) in THF (10 mL) was added NaHMDS (1.0 M in
22
amorphous; [
a
]
D
n
THF, 1.1 mL, 1.1 mmol) at 0 ꢁC. To the reaction mixture was added
;
a solution of aldehyde S2 (174 mg, 180 mmol) in THF (4 mL). After
d
being stirred for 1 h at room temperature, the mixture was
quenched with saturated aqueous NH4Cl, extracted with EtOAc. The
organic layer was washed with brine and dried over Na2SO4. Con-
centration and purification by flash column chromatography
6.89e6.82 (4H, m, MP, p-Tol), 6.02 (1H, dd, J¼10.9, 4.7 Hz, H19), 5.63
(1H, m, H18), 5.38 (1H, s, MP), 4.52 (1H, d, J¼12.3 Hz, NAP), 4.47 (1H,
d, J¼12.3 Hz, NAP), 4.30 (1H, m, H20), 4.09 (1H, dd, J¼16.0, 10.6 Hz,
H22), 3.89e3.69 (7H, m, H1, H5, H11, H130 ꢂ2, H15, H16), 3.58 (1H,
m, H3), 3.47 (2H, m, H21, H22), 3.36 (1H, ddd, J¼9.0, 4.3, 4.3 Hz,
H12), 3.26 (3H, s, MP), 3.22e3.14 (2H, m, H1, H13), 3.08 (1H, ddd,
J¼11.4, 9.4, 4.3 Hz, H6), 2.95e2.83 (2H, m, H8, H13), 2.80 (1H, ddd,
J¼11.6, 3.9, 3.9 Hz, H9), 2.62 (1H, m, H17), 2.51 (1H, ddd, J¼15.0, 4.1,
3.1 Hz, H4), 2.44 (1H, ddd, J¼11.9, 4.3, 4.3 Hz, H7), 2.33 (1H, ddd,
J¼11.6, 4.3, 4.3 Hz, H10), 2.31e2.24 (2H, m, H14, H17), 1.95 (3H, s,
p-Tol), 1.91 (1H, m, H2), 1.84e1.75 (3H, m, H2, H4, H7), 1.63e1.53
(1H, m, H14), 1.43 (1H, ddd, J¼11.6, 11.6, 11.6 Hz, H10); 13C NMR
(hexane/EtOAc 10:1e2:1) gave diene 32 (149 mg, 154
m
mol) in 86%
ꢀ56.6 (c 1.00,
2930, 2857, 1615, 1517, 1461, 1427, 1385, 1249,
1089, 823, 755, 703 cmꢀ1 1H NMR (400 MHz, C6D6)
7.95e7.21
24
yield: colorless amorphous; mp 236e239 ꢁC; [
CHCl3); IR (film)
a]
D
n
;
d
(19H, m, MP, NAP, TBDPS), 6.11 (1H, ddd, J¼17.2, 10.7, 5.3 Hz, H13),
6.04 (1H, dd, J¼11.2, 5.0 Hz, H19), 5.70 (1H, m, H18), 5.63 (1H, ddd,
J¼17.2, 1.6, 1.6 Hz, H140), 5.33, (1H, s, MP), 5.26 (1H, ddd, J¼10.7, 1.6,
1.6 Hz, H140), 4.52 (1H, d, J¼12.3 Hz, NAP), 4.49 (1H, d, J¼12.3 Hz,
NAP), 4.30 (1H, m, H20), 4.12 (1H, dd, J¼10.3, 4.7 Hz, H22),
3.85e3.75 (5H, m, H1, H5, H130 ꢂ2, H15), 3.68 (1H, dddd, J¼9.0, 5.3,
1.6, 1.6 Hz, H12), 3.61e3.51 (2H, m, H3, H21), 3.46 (1H, dd, J¼10.3,
10.3 Hz, H22), 3.30 (1H, m, H16), 3.27 (3H, s, MP), 3.16 (1H, ddd,
J¼12.3, 9.4, 2.5 Hz, H1), 3.04 (1H, ddd, J¼11.4, 9.0, 4.5 Hz, H6),
3.03e2.97 (2H, m, H8, H11), 2.84 (1H, ddd, J¼11.1, 9.0, 4.3 Hz, H9),
2.58e2.53 (3H, m, H4, H7, H17), 2.32 (1H, ddd, J¼11.1, 4.3, 4.3 Hz,
H10), 2.25 (1H, m, H14), 2.15 (1H, ddd, J¼10.6, 6.8, 2.9 Hz, H17),
1.94e1.73 (4H, m, H2 ꢂ2, H4, H7), 1.56 (1H, ddd, J¼11.1, 11.1, 11.1 Hz,
(100 MHz, C6D6)
d 160.5 (C, MP), 143.2 (C, p-Tol), 140.9 (C, p-Tol),
136.9 (C, NAP), 136.0 (CH, H19), 134.0e124.4 (30C, NAP, MP, TBDPS,
p-Tol), 126.5 (CH, C18), 113.8 (CH, p-Tol), 101.1 (CH, MP), 83.69 (CH,
C16), 80.20 (CH, C20), 79.63 (CH, C6), 77.67 (CH, C15), 77.52 (CH,
C5), 77.14 (CH, C8), 76.95 (CH, C12), 76.19 (CH, C21), 75.72 (CH, C9),
74.64 (CH, C11), 73.01 (CH, C3), 70.56 (CH2, NAP), 69.64 (CH2, C22),
66.29 (CH2, C1), 60.72 (CH2, C130), 60.15 (CH2, C13), 54.78 (CH3, MP),
39.06 (CH2, C4), 38.21 (CH2, C10), 37.36 (CH2, C2), 37.27 (CH2, C4),
36.89 (CH2, C7), 30.67 (CH2, C17), 27.19 (CH3 ꢂ3, TBDPS), 21.12 (CH3,
p-Tol), 19.38 (C, TBDPS); HRESIMS m/z 1115.4768 [MþNa]þ (calcd
for C65H76NaO11SSi 1115.4770).
H10), 1.39 (1H, m, H14); 13C NMR (100 MHz, C6D6)
d 160.5 (C, MP),
136.9 (C, NAP), 136.5 (CH, C13), 136.0e126.0 (25C, MP, NAP, TBDPS),
133.5 (CH, C19), 126.7 (CH, C18), 117.1 (CH, C140), 113.8 (CH, MP),
101.2 (CH, MP), 83.76 (CH, C16), 81.29 (CH, C12), 80.23 (CH, C20),
79.72 (CH, C6), 77.93 (CH, C15), 77.77 (CH ꢂ2, C5, C11), 76.62 (CH,
C8), 76.32 (CH, C21), 75.22 (CH, C9), 73.14 (CH, C3), 70.57 (CH2,
NAP), 69.70 (CH2, C22), 66.39 (CH2, C1), 60.60 (CH2, C130), 54.83
(CH3, MP), 39.18 (CH2, C4), 38.08 (CH2, C10), 37.61 (CH2, C7), 36.98
(CH2, C14), 36.85 (CH2, C2), 30.95 (CH2, C17), 27.14 (CH3 ꢂ3, TBDPS),
19.38 (C, TBDPS); HRESIMS m/z 989.4630 [MþNa]þ (calcd for
C59H70NaO10Si 989.4630).
4.1.17. Diene 32. To a mixture of sulfoxide 31 (236 mg, 216
and pyridine (105
L, 1.30 mmol) in CH3CN (4.3 mL) at 0 ꢁC was
added TFAA (90 L, 648 mol). After being stirred 2 h, the mixture
mmol)
m
m
m
was added a solution of KOAc (636 mg, 6.48 mmol) in H2O
(4.0 mL) and stirred for 12 h at room temperature. The mixture
was extracted with EtOAc and the organic layer was washed with
brine, dried over Na2SO4. Concentration and purification by flash
column chromatography (hexane/EtOAc 4:1e1:2) gave the corre-
sponding aldehyde S2 (174 mg, 180
m
mol) in 83% yield: colorless
4.1.18. Alcohol 33. To a solution of diene 32 (149 mg, 150
THF (15 mL) at room temperature was added TBAF (1.0 M in THF,
mmol) in
24
amorphous; [
a
]
D
ꢀ55.2 (c 1.00, CHCl3); IR (film) 2930, 2857,
n

6624
S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
450
m
L, 450
m
mol). After being stirred for 3 h at 35 ꢁC, the mixture
(34.5% in H2O, 2.6 mL, 28.0 mmol) at room temperature. After being
stirred for 10 h at room temperature, the mixture was warmed to
40 ꢁC and stirred for additional 3 h. The mixture was quenched with
saturated aqueous NaHCO3 and Na2S2O3, extracted with EtOAc. The
organic layer was washed with brine and dried over Na2SO4. Con-
centration and purification by column chromatography (hexane/
was quenched with saturated aqueous NH4Cl, extracted with
EtOAc. The organic layer was washed with brine and dried over
Na2SO4. Concentration and purification by flash column chroma-
tography (hexane/EtOAc 5:1e0:1) gave alcohol 33 (111 mg,
152 m
mol) in quantitative yield: colorless solid; mp 174e177 ꢁC;
ꢀ78.2 (c 1.00, CHCl3); IR (film)
25
[
a]
n
3347,2932, 2870, 1615, 1517,
1462, 1382, 1250, 1094, 1039, 821, 755 cmꢀ1 1H NMR (400 MHz,
CDCl3) 7.88e7.79 (4H, m, MP, NAP), 7.52e7.40 (5H, m, MP, NAP),
EtOAc 15:1e2:1) gave triene 5 (163 mg, 230
m
mol) in 82% yield:
D
22
;
colorless solid; mp 194e195 ꢁC; [
a]
ꢀ67.8 (c 1.01, CHCl3); IR (film)
D
d
n
2930, 2868, 1614, 1517, 1440, 1382, 1250, 1091, 1038, 821,
6.88 (2H, d, J¼8.8 Hz, MP), 5.87 (1H, ddd, J¼17.0, 10.7, 6.5 Hz, H13),
5.84 (1H, dd, J¼10.6, 4.3 Hz, H19), 5.74 (1H, m, H18), 5.42 (1H, s,
MP), 5.40 (1H, d, J¼17.0 Hz, H140), 5.28 (1H, d, J¼10.7 Hz, H140), 4.73
(1H, d, J¼12.5 Hz, NAP), 4.70 (1H, d, J¼12.5 Hz, NAP), 4.42 (1H, m,
H20), 4.43 (1H, dd, J¼10.8, 5.2 Hz, H22), 3.99 (1H, ddd, J¼12.7, 10.0,
4.0 Hz, H1), 3.91 (1H, m, H3), 3.80 (3H, s, MP), 3.77e3.71 (2H, m,
H130 ꢂ2), 3.63e3.41 (7H, m, H1, H5, H12, H15, H16, H21, H22),
3.26e3.21 (2H, m, H6, H11), 3.08e3.00 (2H, H8, H9), 2.62 (1H, m,
H17), 2.45e2.33 (4H, m, H4, H7, H10, H17), 2.15e1.95 (3H, m, H2 ꢂ2,
H14), 1.87 (1H, ddd, J¼14.4, 9.6, 3.2 Hz, H4), 1.58e1.45 (3H, H7, H10,
754 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.88e7.79 (4H, m, NAP),
7.54e7.40 (5H, m, MP, NAP), 6.91 (2H, d, J¼8.8 Hz, MP), 5.98 (1H,
ddd, J¼17.1, 10.6, 4.3 Hz, H14), 5.90 (1H, dd, J¼11.0, 6.5 Hz, H19),
5,87 (1H, ddd, J¼17.4, 7.6, 6.1 Hz, H13), 5.75 (1H, dddd, J¼12.1, 12.1,
6.5, 1.6 Hz, H18), 5.44 (1H, s, MP), 5.38 (1H, ddd, J¼17.4, 1.5, 1.5 Hz,
H140), 5.27 (1H, ddd, J¼17.1, 1.8, 1.8 Hz, C130), 5.24 (1H, ddd, J¼7.6,
1.5, 1.5 Hz, H140), 5.10 (1H, ddd, J¼10.6, 1.8, 1.8 Hz, H130), 4.74 (1H, d,
J¼12.3 Hz, NAP), 4.69 (1H, d, J¼12.3 Hz, NAP), 4.44 (1H, ddd, J¼11.0,
4.9, 1.6 Hz, H20), 4.30 (1H, dd, J¼11.0, 5.3 Hz, H22), 3.98 (1H, ddd,
J¼12.7, 6.1, 3.9 Hz, H1), 3.91 (1H, m, H3), 3.85 (1H, m, H15), 3.80 (3H,
s, MP), 3.66 (1H, dd, J¼11.0, 11.0 Hz, H22), 3.63e3.47 (4H, m, H1, H5,
H12, H16), 3.41 (1H, ddd, 11.0, 11.0, 5.3 Hz, H21), 3.23 (2H, ddd,
J¼11.1, 9.2, 4.5 Hz, H6, H11), 3.06 (1H, ddd, J¼11.4, 9.0, 4.3 Hz, H8),
3.00 (1H, ddd, J¼11.1, 9.2, 4.1 Hz, H9), 2.65 (1H, ddd, J¼12.1, 9.4,
2.7 Hz, H17), 2.48e2.32 (4H, m, H4, H7, H10, H17), 2.09 (1H, dddd,
J¼14.9, 6.1, 6.1, 2.9 Hz, H2), 1.99 (1H, dddd, J¼14.9, 8.8, 7.2, 4.1 Hz,
H2),1.87 (1H, ddd, J¼13.1, 9.8, 3.5 Hz, H4),1.55 (1H, ddd, J¼11.4,11.4,
11.4 Hz, H7), 1.52 (1H, ddd, J¼11.1, 11.1, 11.1 Hz, H10); 13C NMR
H14); 13C NMR (100 MHz, CDCl3)
d 160.1 (C, MP), 136.2 (C, NAP),
135.7 (CH, C13), 133.4 (CH, C19), 133.38e133.0 (C ꢂ2, NAP, MP),
130.1 (C, NAP), 128.2e126.3 (CH, ꢂ5, NAP, MP), 126.2 (CH, C18),
126.2 (CH, NAP), 125.9 (CH, NAP), 125.7 (CH, NAP), 119.1 (CH, C140),
113.7 (CH, MP), 100.8 (CH, MP), 83.43 (CH, C16), 81.47 (CH, C15),
79.79 (CH, C20), 78.81 (CH, C12), 78.67 (CH, C6), 77.32 (CH, C5),
77.01 (CH, C11), 76.04 (CH, C9), 75.91 (CH, C21), 75.78 (CH, C8),
72.60 (CH, C3), 70.51 (CH2, NAP), 69.41 (CH2, C22), 66.43 (CH2, C1),
59.52 (CH2, C130), 55.33 (CH3, MP), 38.39 (CH2, C4), 37.62 (CH2, C10),
36.83 (CH2, C7), 36.23 (CH2, C2), 36.04 (CH2, C14), 30.09 (CH2, C17);
HRESIMS m/z 751.3453 [MþNa]þ (calcd for C43H52NaO10 751.3454).
(100 MHz, CDCl3)
d 160.1 (C, MP), 137.1 (CH, C14), 136.2 (C, NAP),
135.6 (CH, C13), 133.7 (CH, C19), 133.3e125.7 (12C, MP, NAP),
126.3 (CH, C18), 118.4 (CH, C140), 114.7 (CH, C13), 113.7 (CH ꢂ2, MP),
100.9 (CH, MP), 83.13 (CH, C16), 81.22 (CH, C12), 81.13 (CH, C15),
79.87 (CH, C20), 78.86 (CH, C6), 77.35 (CH, C5), 77.31 (CH, C11),
76.10 (CH, C8), 75.80 (CH, C9), 75.54 (CH, C21), 72.64 (CH, C3), 70.55
(CH2, NAP), 69.57 (CH2, C22), 66.44 (CH2, C1), 55.37 (CH3, MP),
38.44 (CH2, C4), 37.46 (CH2, C10), 36.87 (CH2, C7), 36.28 (CH2, C2),
30.74 (CH2, C17); HRESIMS m/z 733.3350 [MþNa]þ (calcd for
C43H50NaO9 733.3347).
4.1.19. Selenide 34. To a mixture of alcohol 33 (204 mg, 280
and PhSeCN (344 L, 2.80 mmol) in THF (56 mL) was added n-Bu3P
(699 L, 2.80 mmol). After being stirred 1 h, the mixture was
quenched with saturated aqueous NaHCO3, extracted with EtOAc.
The organic layer was washed with brine and dried over Na2SO4.
Concentration and purification by flash column chromatography
mmol)
m
m
(hexane/EtOAc 10:1e2:1) gave selenide 34 (245 mg, 280
m
mol) in
ꢀ68.0 (c
2931, 2869, 1615, 1517, 1438, 1382, 1249,
1103, 1039, 823, 752 cmꢀ1 1H NMR (400 MHz, CDCl3)
7.84e7.78
24
quantitative yield: colorless solid; mp 66e70 ꢁC; [
1.02, CHCl3); IR (film)
a
]
4.1.21. Diol 36. To a solution of 5 (84.6 mg, 119
mmol) in CH2Cl2
D
n
(60 mL) was added Grubbs’ catalyst 35 (49 mg, 60
m
mol). After
;
d
being stirred for 12 h under reflux conditions, the reaction mixture
was quenched with Et3N at room temperature. After being stirred
for 10 h at room temperature, the mixture was concentrated under
reduced pressure. The resultant residue was purified by flash col-
umn chromatography (hexane/EtOAc 5:1e1:1) to give diene S3
(4H, m, MP, NAP), 7.52e7.25 (10H, m, MP, NAP, Ph), 6.88 (2H, d,
J¼8.8 Hz, MP), 5.86 (1H, dd, J¼11.0, 4.9 Hz, H19), 5.75 (1H, m, H18),
5.71 (1H, ddd, J¼17.2, 10.5, 6.6 Hz, H13), 5.41 (1H, s, MP), 5.22 (1H,
ddd, J¼17.2, 1.2, 1.2 Hz, H140), 5.11 (1H, ddd, J¼10.5, 1.2, 1.2 Hz, H140),
4.73 (1H, d, J¼12.5 Hz, NAP), 4.70 (1H, d, J¼12.5 Hz, NAP), 4.40 (1H,
m, H20), 4.25 (1H, dd, J¼10.8, 5.1 Hz, H22), 3.95 (1H, ddd, J¼12.7,
10.0, 3.9 Hz, H1), 3.91 (1H, m, H3), 3.80 (3H, s, MP), 3.59 (1H, dd,
J¼10.8, 10.8 Hz, H22), 3.56e3.38 (6H, m, H1, H5, H12, H15, H16,
H21), 3.25e3.18 (2H, m, H6, H11), 3.06e2.94 (3H, m, H8, H9, H130),
2.85 (1H, ddd, J¼16.4, 8.8, 7.5 Hz, H130), 2.58 (1H, m, H7), 2.43e2.32
(4H, m, H4, H7, H10, H17), 2.13e2.07 (2H, m, H2, H14), 1.99 (1H, m,
H2), 1.87 (1H, ddd, J¼14.7, 9.8, 3.3 Hz, H4), 1.67 (1H, m, H14),
(71.5 mg, 105 m
mol) in 88% yield: colorless solid; mp 236e239 ꢁC;
22
D
[a
]
ꢀ98.1 (c 0.48, CHCl3); IR (film)
n
2931, 2876, 1614, 1518, 1440,
1388, 1173, 1101, 998, 831, 750 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
7.85e7.79 (4H, m, NAP), 7.52e7.41 (5H, m, MP, NAP), 6.91 (2H, d,
J¼8.8 Hz, MP), 5.88e5.80 (2H, m, H18, H19), 5.74 (1H, ddd, J¼12.7,
1.4, 1.4 Hz, H13), 5.57 (1H, ddd, J¼12.7, 1.2, 1.2 Hz, H14), 5.43 (1H, s,
MP), 4.74 (1H, d, J¼12.3 Hz, NAP), 4.71 (1H, d, J¼12.3 Hz, NAP), 4.43
(1H, dd, J¼8.8, 2.4 Hz, H20), 4.27 (1H, dd, J¼10.8, 5.1 Hz, H22), 4.18
(1H, dd, J¼8.6, 2.1 Hz, H15), 3.99 (1H, ddd, J¼12.7, 6.0, 3.9 Hz, H1),
3.90 (1H, m, H3), 3.80 (3H, s, MP), 3.78 (1H, m, H12), 3.64 (1H, m,
H16), 3.62 (1H, dd, J¼10.8, 10.8 Hz, H22), 3.55e3.45 (3H, m, H1, H5,
H21), 3.25 (1H, ddd, J¼13.5, 9.0, 4.5 Hz, H11), 3.20 (1H, ddd, J¼13.3,
9.2, 4.3 Hz, H6), 2.99e2.92 (2H, m, H8, H9), 2.73 (1H, ddd, J¼12.7,
8.8, 3.7 Hz, H17), 2.41e2.25 (3H, m, H4, H7, H17), 2.23 (1H, ddd,
J¼13.5, 4.5, 4.5 Hz, H10), 2.09 (1H, dddd, J¼15.1, 6.0, 6.0, 3.1 Hz, H2),
1.97 (1H, ddd, J¼15.1, 8.6, 6.7, 3.9 Hz, H2), 1.89 (1H, ddd, J¼14.5, 9.6,
3.3 Hz, H4), 1.52 (1H, ddd, J¼13.3, 13.3, 13.3 Hz, H7), 1.46 (1H, ddd,
1.55e1.46 (2H, m, H7, H10); 13C NMR (100 MHz, CDCl3)
d 160.1 (C,
MP), 136.2 (C, NAP), 135.5 (CH, C13), 133.4 (CH, C19), 133.3e125.7
(ꢂ18, MP, NAP, Ph), 126.2 (CH, C18), 119.4 (CH, C140), 113.7 (CH ꢂ2,
MP), 100.8 (CH, MP), 83.64 (CH, C21), 81.57 (CH, C12), 80.99 (CH,
C15), 79.79 (CH, C20), 78.84 (CH, C6), 77.35 (CH, C5), 77.15 (CH, C11),
76.27 (CH, C16), 76.06 (CH, C9), 75.78 (CH, C8), 72.61 (CH, C3), 70.54
(CH2, NAP), 69.41 (CH2, C22), 66.46 (CH2, C1), 55.37 (CH3, MP),
38.44 (CH2, C4), 37.62 (CH2, C7), 36.87 (CH2, C10), 36.26 (CH2, C2),
34.62 (CH2, C14), 30.20 (CH2, C17), 22.83 (CH2, C130); HRESIMS m/z
891.2980 [MþNa]þ (calcd for C49H56NaO9Se 891.2982).
J¼13.5, 13.5, 13.5 Hz, H10); 13C NMR (100 MHz, C6D6)
d 160.2 (C,
MP), 136.2 (C, NAP), 135.2 (CH, C13), 133.7 (C, NAP), 133.1 (CH, C19),
133.1 (C, NAP), 131.0 (CH, C14), 130.2 (C, MP), 128.3 (CH, NAP), 127.9
(CH, NAP), 127.8 (CH, NAP), 127.5 (CH ꢂ2, MP), 127.0 (CH, C18), 126.3
4.1.20. Triene 5. To a mixture of selenide 34 (245 mg, 280 mmol)
and NaHCO3 (470 mg, 5.6 mmol) in THF (56 mL) was added H2O2

S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
6625
(CH, NAP), 126.2 (CH, NAP), 125.9 (CH, NAP), 125.8 (CH, NAP),
113.7 (CH ꢂ2, MP), 100.8 (CH, MP), 85.01 (CH, C16), 81.05 (CH, C15),
80.64 (CH, C12), 79.76 (CH, C20), 78.86 (CH, C6), 78.57 (CH, C11),
77.32 (CH, C5), 76.12 (CH, C8), 76.00 (CH, C9), 75.93 (CH, C21), 72.63
(CH, C3), 70.56 (CH2, NAP), 69.76 (CH2, C22), 66.45 (CH2, C1),
55.40 (CH3, MP), 38.50 (CH2, C4), 36.98 (CH2, C10), 36.80 (CH2, C7),
36.31 (CH2, C2), 32.76 (CH2, C17); HRESIMS m/z 705.3035 [MþNa]þ
(calcd for C41H46NaO9 705.3034).
3.9 Hz, H2), 1.75 (1H, ddd, J¼14.6, 9.6, 3.5 Hz, H4), 1.38 (1H, ddd,
J¼11.4, 11.4,11.4 Hz, H7), 1.30 (1H, ddd, J¼11.3, 11.3, 11.3 Hz, H10); 13C
NMR (100 MHz, CDCl3) d 145.0 (C, Ts),136.2 (C, NAP),135.6 (CH, C19),
134.9 (CH, C13),133.3 (C, NAP),130.0 (C, Ts),133.0 (C, NAP),130.7 (NH,
C14), 130.0 (CH ꢂ2, Ts), 128.3 (CH, NAP), 128.1 (CH ꢂ2, Ts), 127.9 (CH,
NAP), 127.8 (CH, NAP), 127.5 (CH,C18), 126.3 (CH, NAP), 126.2 (CH,
NAP), 125.9 (CH, NAP), 125.8 (CH, NAP), 84.57 (CH, C16), 83.29 (CH,
C21), 81.54 (CH, C15), 80.71 (CH, C12), 78.87 (CH, C6), 78.49 (CH, C11),
77.32 (CH, C5), 76.12 (CH, C9), 75.92 (CH, C8), 72.64 (CH, C3),
71.31 (CH2, C22), 70.57 (CH2, NAP), 68.62 (CH, C20), 66.45 (CH2, C1),
38.50 (CH2, C4), 36.79 (CH2, C7), 36.31 (CH2, C2), 32.58 (CH2, C17),
21.79 (CH2, Ts); HRESIMS m/z 741.2703 [MþNa]þ (calcd for
C40H46NaO10S 741.2704).
To a solution of the above diene S3 (71.5 mg, 105
mmol) in CH2Cl2
(10 mL) and MeOH (10 mL) was added CSA (2.4 mg, 10
m
mol). After
being stirred for 10 h, the mixture was quenched with saturated
aqueous NaHCO3 and extracted with EtOAc. The organic layer was
washed with brine and dried over Na2SO4. Concentration and pu-
rification by flash column chromatography (hexane/EtOAc 3:1e1:5)
To a solution of the above tosylate S4 (110 mg,153 mmol) in DMSO
gave diol 36 (51 mg, 90
m
mol) in 86% yield: colorless solid; mp
ꢀ95.6 (c 0.99, CHCl3); IR (film) 3394, 2930,
2871, 1454, 1353, 1284, 1094, 1076, 753 cmꢀ1 1H NMR (400 MHz,
CDCl3) 7.84e7.78 (4H, m, NAP), 7.52e7.45 (3H, m, NAP), 5.82e5.71
(22 mL) at room temperature was added NaCN (75 mg, 1.53 mmol).
After being stirred for 20 h at 45 ꢁC, the reaction mixture was
quenched with EtOAc and saturated aqueous NaHCO3. The mixture
was extracted with EtOAc (ꢂ3), and the organic layer was washed
with brine and dried over Na2SO4. Concentration and purification by
22
198e202 ꢁC; [
a
]
n
D
;
d
(3H, m, H13, H18, H19), 5.56 (1H, ddd, J¼12.7, 2.3, 2.3 Hz, H14), 4.74
(1H, d, J¼12.2 Hz, NAP), 4.70 (1H, d, J¼12.2 Hz, NAP), 4.46 (1H, dd,
J¼9.2, 4.7 Hz, H20), 4.13 (1H, dd, J¼9.0, 2.3 Hz, H15), 3.97 (1H, ddd,
J¼12.7, 6.0, 3.9 Hz, H1), 3.91e3.88 (2H, m, H3, H21), 3.80e3.74 (2H,
m, H12, H22), 3.60 (1H, ddd, J¼9.0, 3.7, 3.0 Hz, H16), 3.54e3.49 (2H,
m, H1, H5), 3.41 (1H, ddd, J¼9.4, 4.7, 4.1 Hz, H21), 3.27e3.18 (2H, m,
H6, H11), 2.98e2.91 (2H, m, H8, H9), 2.69 (1H, ddd, J¼12.9, 9.0,
3.7 Hz, H17), 2.38 (1H, ddd, J¼14.7, 4.5, 3.7 Hz, H4), 2.33e2.27 (2H,
m, H7, H17), 2.22 (1H, ddd, J¼11.9, 3.7, 3.7 Hz, H10), 2.09 (1H, dddd,
J¼15.2, 6.0, 6.0, 3.3 Hz, H2), 1.97 (1H, dddd, J¼15.2, 8.8, 6.9, 3.9 Hz,
H2), 1.87 (1H, ddd, J¼14.7, 9.4, 3.3 Hz, H4), 1.58 (2H, br, OH ꢂ2), 1.50
(1H, ddd, J¼11.3, 11.3, 11.3 Hz, H7), 1.45 (1H, ddd, J¼11.9, 11.9,
column chromatography (hexane/EtOAc 10:1e1:1) gave nitrile 37
22
(78 mg, 136
ꢀ97.7 (c 0.37, CH2Cl2); IR (film)
1283, 1093, 909, 737 cmꢀ1; 1H NMR (400 MHz, CDCl3)
m a]
mol) in 89% yield: colorless solid; mp 113 ꢁC; [
D
n
3381, 2932, 2872, 2248,1438,1353,
7.84e7.78
d
(4H, m, NAP), 7.49e7.46 (3H, m, NAP), 5.93 (1H, ddd, J¼10.2, 2.6,
2.6 Hz, H13), 5.85 (1H, dddd, J¼11.0, 10.4, 6.4, 1.4 Hz, H18), 5.67 (1H,
dd, J¼11.0, 5.0 Hz, H19), 5.58 (1H, ddd, J¼10.2, 2.4, 2.4 Hz, H14), 4.73
(1H, d, J¼12.5 Hz, NAP), 4.69 (1H, d, J¼12.5 Hz, NAP), 4.27 (1H, m,
H20), 4.13 (1H, ddd, J¼8.6, 2.6, 2.4 Hz, H15), 3.97 (1H, ddd, J¼12.7, 6.0,
3.9 Hz, H1), 3.90 (1H, dddd, J¼9.6, 7.3, 6.0, 3.7 Hz, H3), 3.74 (1H, ddd,
J¼10.2, 2.6, 2.4 Hz, H12), 3.61 (1H, ddd, J¼8.6, 31.1, 3.1 Hz, H16), 3.57
(1H, ddd, J¼8.6, 8.6, 3.1 Hz, H21), 5.54 (1H, ddd, J¼9.2, 4.6, 3.3 Hz,
H5), 3.50 (1H, ddd, J¼12.7, 9.0, 3.1 Hz, H1), 3.23 (1H, ddd, J¼11.3, 9.0,
4.7 Hz, H11), 3.21 (1H, ddd, J¼11.3, 9.2, 4.5 Hz, H6), 2.98e2.91 (2H, m,
H9, H8), 2.90 (1H, dd, J¼16.8, 3.1 Hz, H22), 2.69 (1H, ddd, J¼10.4,10.4,
3.1 Hz, H17), 2.58 (1H, dd, J¼16.8, 8.6 Hz, H22), 2.38 (1H, ddd, J¼14.7,
4.6, 3.7 Hz, H4), 2.33e2.29 (2H, m, H7, H17), 2.22 (1H, ddd, J¼11.3, 4.7,
4.7 Hz, H10), 2.09 (1H, dddd, J¼15.3, 6.0, 6.0, 3.1 Hz, H2), 1.97 (1H,
dddd, J¼15.3, 9.0, 7.3, 3.9 Hz, H2), 1.85 (1H, ddd, J¼14.7, 9.6, 3.3 Hz,
H4),1.56 (1H, s, OH),1.51 (1H, ddd, J¼11.3,11.3,11.3 Hz, H7),1.43 (1H,
11.9 Hz, H10); 13C NMR (100 MHz, CDCl3)
d 136.5 (C, C19), 136.2 (C,
NAP), 135.1 (CH, C13), 133.4 (C, NAP), 133.1 (C, NAP), 130.9 (CH, C14),
128.3 (CH, NAP), 127.9 (CH, NAP), 127.8 (CH, NAP), 126.8 (CH, C18),
126.4 (CH, NAP), 126.2 (CH, NAP), 126.0 (CH, NAP), 125.8 (CH, NAP),
85.06 (CH, C21), 84.79 (CH, C16), 81.20 (CH, C15), 80.69 (CH, C12),
78.85 (CH, C6), 78.53 (CH, C11), 77.31 (CH, C5), 76.10 (CH, C9), 75.93
(CH, C8), 72.61 (CH, C3), 70.56 (CH2, NAP), 70.16 (CH, C20),
66.44 (CH2, C1), 64.53 (CH2, C22), 38.47 (CH2, C4), 36.96 (CH2, C10),
36.77 (CH2, C7), 36.27 (CH2, C2), 32.63 (CH2, C17); HRESIMS m/z
587.2614 [MþNa]þ (calcd for C33H40NaO8 587.2615).
ddd, J¼11.3,11.3,11.3 Hz, H10); 13C NMR (100 MHz, CDCl3)
d 136.2 (C,
NAP), 135.4 (CH,C19), 134.4 (CH, C13), 133.4 (C, NAP), 133.1 (C, NAP),
131.1 (CH, C14), 128.6 (CH, C18), 128.3 (CH, NAP), 127.9 (CH, NAP),
127.8 (CH, NAP), 126.4 (CH,NAP), 126.2 (CH, NAP), 126.0 (CH, NAP),
125.8 (CH, NAP),118.3 (C, CN), 84.25 (CH, C16), 81.49 (CH, C15), 81.42
(CH, C21), 80.73 (CH, C12), 78.88 (CH, C6), 78.52 (CH, C11), 77.32 (CH,
C5), 76.14 (CH, C9), 75.91 (CH, C8), 72.65 (CH, C3), 71.44 (CH, C20),
70.57 (CH2, NAP), 66.45 (CH2, C1), 38.52 (CH2, C4), 36.98 (CH2, C10),
36.78 (CH2, H7), 36.30 (CH2, C2), 32.63 (CH2, C17), 22.78 (CH2, C22);
HRESIMS m/z 596.2619 [MþNa]þ (calcd for C34H39NNaO7 596.2619).
4.1.22. Nitrile 37. To a solution of diol 36 (41.6 mg, 73.7
pyridine (7.4 mL) at room temperature was added TsCl (140 mg,
737 mol). After being stirred for 8 h, the reaction mixture was
quenched and saturated aqueous NaHCO3. The mixture was extrac-
ted with EtOAc (ꢂ3), and the organic layer was washed with brine
and dried over Na2SO4. Concentration and purification by column
chromatography (hexane/EtOAc 2:1e1:1) gave the corresponding
mmol) in
m
tosylate S4 (46.6 mg, 64.9
m
mol) in 88% yield: colorless solid; mp
ꢀ92.2 (c 0.75, CH2Cl2); IR (film) 3455, 2931, 2871,1598,
1H NMR (400 MHz, CDCl3)
7.73e7.67 (6H, m, NAP, Ts), 7.41e7.35 (3H, m, NAP), 7.23 (2H, d,
22
94 ꢁC; [
a]
D
n
1356, 1094, 1074, 814, 754 cmꢀ1
;
4.1.23. C-CTX left wing 4. To a solution of the nitrile 37 (53.1 mg,
d
92.6
hexane, 370
m
mol) in CH2Cl2 (9.3 mL) at ꢀ78 ꢁC was added DIBAL (1.0 M in
J¼9.6 Hz, Ts), 5.66 (1H, dddd, J¼11.2, 10.9, 6.7, 1.9 Hz, H18), 5.57 (1H,
ddd, J¼12.7, 2.7, 2.7 Hz, H13), 5.55 (1H, dd, J¼11.2, 5.7 Hz, H19), 5.39
(1H, ddd, J¼12.7, 2.3, 2.3 Hz, H14), 4.63 (1H, d, J¼12.5 Hz, NAP), 4.58
(1H, d,J¼12.5Hz,NAP), 4.27(1H, ddd, J¼9.4, 5.7,1.9Hz,H20), 4.18(2H,
d, J¼3.9 Hz, H22), 3.90 (1H, ddd, J¼10.9, 2.7, 2.3 Hz, H15), 3.87 (1H,
ddd, J¼12.7, 6.0, 3.9 Hz, H1), 3.78(1H, dddd, J¼9.6, 6.8, 4.7, 3.6 Hz, H3),
3.60 (1H, ddd, J¼11.3, 4.7, 2.7 Hz, H12), 3.44 (1H, ddd, J¼11.4, 3.5,
3.5 Hz, H5), 3.42 (1H, ddd, J¼10.9, 3.5, 2.5 Hz, H16), 3.39 (1H, ddd,
J¼12.7, 8.8, 8.6 Hz, H1), 3.35 (1H, dt, J¼9.4, 3.9 Hz, H21), 3.10 (1H, ddd.
J¼11.4, 11.4, 3.9 Hz, H6), 3.08 (1H, ddd, J¼11.3, 11.3, 4.7 Hz, H11),
2.84e2.81 (2H, m, H8, H9), 2.50 (1H, ddd, J¼13.7, 10.9, 3.5 Hz, H17),
2.34 (3H, s, Ts), 2.27 (1H, ddd, J¼14.6, 4.7, 3.5 Hz, H4), 2.20 (1H, ddd,
J¼13.7, 6.7, 2.5 Hz, H7), 2.08 (1H, ddd, J¼11.3, 4.7, 4.7 Hz, H10), 2.00
(1H, dddd, J¼15.4, 8.8, 6.0, 3.6 Hz, H2),1.86 (1H, dddd, J¼15.5, 8.6, 6.8,
mL, 370
m
mol). After being stirred for 1 h at ꢀ78 ꢁC, the
reaction mixture was quenched with EtOAc and saturated aqueous
Rochell’s salt. The mixture was extracted with EtOAc (ꢂ3), and the
organic layer was washed with brine and dried over Na2SO4. Con-
centration and filtration through a pad of flash silica gel gave the
aldehyde, which was used in the next reaction without further
purification.
To a suspension of Ph3PCH3Br (200 mg, 556 mmol) in THF
(4.6 mL) at 0 ꢁC was added NaHMDS (1.0 M in THF, 370
mL,
370
mmol). After being stirred for 1 h, a solution of the above al-
dehyde in THF (4 mL) was added to the reaction mixture at 0 ꢁC.
After being stirred for 1 h at room temperature, the reaction mix-
ture was quenched with aqueous saturated NH4Cl. The mixture was
extracted with EtOAc (ꢂ3), and the organic layer was washed with

6626
S. Yamashita et al. / Tetrahedron 67 (2011) 6616e6626
Botana, L. M. Anal. Chem. 2010, 82, 6032e6039; (c) Yogi, K.; Oshiro, N.; Inafuku,
Y.; Hirama, M.; Yasumoto, T., submitted for publication.
brine and dried over Na2SO4. Concentration and purification by
column chromatography (hexane/EtOAc 10:1e3:1) gave the left
6. (a) Yasumoto, T.; Igarashi, T.; Legrand, A.-M.; Cruchet, P.; Chinain, M.; Fujita, T.;
Naoki, H. J. Am. Chem. Soc. 2000, 122, 4988e4989; (b) Satake, M.; Murata, M.;
Yasumoto, T. Tetrahedron Lett. 1993, 34, 1975e1978; (c) Satake, M.; Fukui, M.;
Legrand, A.-M.; Cruchet, P.; Yasumoto, T. Tetrahedron Lett. 1998, 39, 1197e1198.
7. (a) Hirama, M.; Oishi, T.; Uehara, H.; Inoue, M.; Maruyama, M.; Oguri, H.; Satake,
M. Science 2001, 294, 1904e1907; (b) Inoue, M.; Uehara, H.; Maruyama, M.;
Hirama. Org. Lett. 2002, 4, 4551e4554; (c) Inoue, M.; Miyazaki, K.; Uehara, H.;
Maruyama, M.; Hirama, M. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 12013e12018;
(d) Inoue, M.; Hirama, M. Synlett 2004, 577e595; (e) Inoue, M.; Hirama, M. Acc.
Chem. Res. 2004, 37, 961e968; (f) Hirama, M. Chem. Rec. 2005, 5, 240e250; (g)
Inoue, M.; Miyazaki, K.; Ishihara, Y.; Tatami, A.; Ohnuma, Y.; Kawada, Y.;
Komano, K.; Yamashita, S.; Lee, N.; Hirama, M. J. Am. Chem. Soc. 2006, 128,
9352e9354; (h) Yamashita, S.; Ishihara, Y.; Morita, H.; Uchiyama, J.; Takeuchi,
K.; Inoue, M.; Hirama, M. J. Nat. Prod. 2011, 74, 357e364.
wing fragment 4 (38.2 mg, 66.5 mmol) in 72% yield over two steps:
22
colorless solid; mp 91 ꢁC; [
a
]
ꢀ91.9 (c 1.07, CHCl3); IR (film)
n
D
3448, 2930, 2871, 1723, 1641, 1453, 1437, 1353, 1090, 753 cmꢀ1; 1H
NMR (400 MHz, CDCl3) 7.84e7.78 (4H, m, NAP), 7.49e7.46 (3H, m,
d
NAP), 5.93 (1H, dddd, J¼16.8, 10.2, 7.4, 6.4 Hz, H23), 5.81e5.73 (2H,
m, H13, H18), 5.69 (1H, dd, J¼11.0, 4.9 Hz, H19), 5.52 (1H, ddd,
J¼12.7, 2.5, 2.5 Hz, H14), 5.15 (1H, dd, J¼16.8, 1.9 Hz, H24), 5.11 (1H,
dd, J¼7.4, 1.9 Hz, H24), 4.74 (1H, d, J¼12.5 Hz, NAP), 4.69 (1H, d,
J¼12.5 Hz, NAP), 4.22 (1H, m, H20), 4.06 (1H, ddd, J¼8.8, 56.1,
2.5 Hz, H15), 3.98 (1H, ddd, J¼12.7, 6.0, 3.7 Hz, H1), 3.89 (1H, m, H3),
3.74 (1H, ddd, J¼9.2, 4.5, 2.5 Hz, H12), 3.59 (1H, ddd, J¼8.8, 3.5,
3.5 Hz, H16), 3.55e3.48 (2H, m, H1, H5), 3.33 (1H, ddd, J¼9.0, 9.0,
2.9 Hz, H21), 3.23 (1H, ddd, J¼11.4, 9.2, 4.7 Hz, H11), 3.19 (1H, ddd,
J¼11.4, 9.1, 4.4 Hz, H6), 2.97e2.90 (2H, m, H8, H9), 2.71 (1H, ddd,
J¼13.1, 9.4, 3.5 Hz, H17), 2.63 (1H, ddd, J¼12.8, 6.4, 2.9 Hz, H22),
2.38 (1H, ddd, J¼14.7, 4.7, 3.7 Hz, H4), 2.34e2.17 (4H, m, H7, H10,
H17, H22), 2.10 (1H, dddd, J¼15.2, 6.0, 6.0, 3.0 Hz, H2), 1.99 (1H,
dddd, J¼15.3, 8.6, 6.8, 3.7 Hz, H2), 1.87 (1H, ddd, J¼14.7, 9.6, 3.5 Hz,
H4), 1.63 (1H, s, OH), 1.51 (1H, ddd, J¼11.4, 11.4, 11.4 Hz, H7), 1.43
(1H, ddd, J¼11.4, 11.4, 11.4 Hz, H10); 13C NMR (100 MHz, CDCl3)
8. (a) Oguri, H.; Hirama, M.; Tsumuraya, T.; Fujii, I.; Maruyama, M.; Uehara, H.;
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d
136.6 (CH, C19), 136.2 (C, NAP), 135.5 (CH, C23), 135.4 (CH, C13),
133.4 (C, NAP), 133.1 (C, NAP), 130.6 (CH, C14), 128.3 (CH, NAP),
128.0 (CH, NAP), 127.8 (CH, NAP), 127.0 (CH, C18), 126.3 (CH, NAP),
126.2 (CH, NAP), 126.0 (CH, NAP), 125.8 (CH, NAP), 117.3 (CH, C24),
85.75 (CH, C21), 84.70 (CH, C16), 81.13 (CH, C15), 80.81 (CH,
C12), 78.92 (CH, C6), 78.49 (CH, C11), 77.32 (CH, C5), 76.13 (CH, C9),
75.98 (CH, C8), 72.65 (CH, C3), 72.22 (CH, C20), 70.58 (CH2, NAP),
66.47 (CH2, C1), 38.05 (CH2, C4), 37.51 (CH2, C22), 37.01 (CH2, C10),
36.83 (CH2, C7), 36.35 (CH2, C2), 32.68 (CH2, C17); HRESIMS m/z
597.2824 [MþNa]þ (calcd for C35H42NaO7 597.2823).
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Acknowledgements
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This work was supported financially by a Grant-in-Aid for Spe-
cially Promoted Research from Ministry of Education, Culture,
Sports, Science and Technology (MEXT) in Japan. We thank the
editor for his courtesy and extension of the deadline for submission
upon considering the recent earthquake at Tohoku, the northern
part of Japan’s main island.
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Supplementary data
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Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.05.080.
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