Synthesis of a spiroacetal moiety of antitumor antibiotic ossamycin by anodic oxidation

Article abstract of DOI:10.1016/j.tet.2008.07.078

Synthesis of the spiroacetal moiety (C20-C33) of the antitumor antibiotic ossamycin, is reported. Anodic oxidation of the dithioacetal effected simultaneous removal of the protecting group and acetalization to afford the corresponding 6,6-spiroacetal structure in excellent yield.

Full text of DOI:10.1016/j.tet.2008.07.078

Tetrahedron 64 (2008) 9495–9506
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Synthesis of a spiroacetal moiety of antitumor antibiotic
ossamycin by anodic oxidation
*
Eriko Honjo, Noriki Kutsumura, Yuichi Ishikawa, Shigeru Nishiyama
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthesis of the spiroacetal moiety (C20–C33) of the antitumor antibiotic ossamycin, is reported. Anodic
oxidation of the dithioacetal effected simultaneous removal of the protecting group and acetalization to
afford the corresponding 6,6-spiroacetal structure in excellent yield.
Received 16 April 2008
Received in revised form 18 July 2008
Accepted 18 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Available online 23 July 2008
Keywords:
Antibiotics
Ossamycin
Spiroacetal
Anodic oxidation
1. Introduction
Here, we describe an electrochemical approach to the spiroacetal-
containing system 1, which is ascribed to the C20–C33 segment of
Spiroacetals are present in a wide range of macrolide antibiotics,
such as ossamycin,1 cytovaricin,2 dunaimycins,3 A82548A,4 and
oligomycins.5 Their 3-D structures have been investigated with
regard to stereoselective construction and biological effects such as
antimicrobial, antitumor, and enzymatic inhibitory activities
(Fig. 1). As part of our ongoing synthetic investigations, we have
developed a method for synthesis of ossamycin, an antitumor an-
tibiotic isolated from Streptomyces hygroscopicus var. ossamyceticus.
We have already reported the synthesis of the C1–C16 segment (the
polyol subunit) carrying seven contiguous stereogenic centers,
along with synthesis of the ossamine derivatives and its glycosyl-
ation properties (Scheme 1).6 As the next step, the C17–C33 seg-
ment involving the spiroacetal moiety (the spiroacetal subunit)
would be constructed (Scheme 2). Generally, construction of spi-
rostructures has been accomplished using the corresponding
dihydroxy-ketone precursors or dihydroxy-acetals in the presence
of acid catalysts.7 When dithiane precursors were utilized,8 how-
ever, toxic and hazardous chemicals, such as HgCl2,9 MeI,10 NBS,11
and PIFA,12 were required to remove sulfur functions (Scheme 3). In
contrast, using an electrochemical procedure, reactions may
proceed efficiently under mild conditions.13 Such methods can
control the amounts of active species and generate less toxic re-
agents than the standard chemical methods, mentioned above.
ossamycin, by utilizing anodic oxidation.
2. Results and discussion
2.1. Synthesis of 3
First, we synthesized the spiroacetal 3 as a model to study
construction of the spiroacetal structure 1. As can be seen in
Scheme 4, the spiroacetal 3 would be produced by coupling of the
epoxide 5 and dithiane 6, followed by cyclization of the dithioacetal
4. Epoxide 5 and dithiane 6 would be produced from the known
diol 714 and the known alcohol 8,15 respectively.
Based on the above-mentioned retrosynthetic analysis, syn-
thesis of the epoxide 5 was commenced with selective protection of
the known diol 7 (Scheme 5). Thus, 7 was protected as a p-
methoxybenzylidene acetal, followed by reductive cleavage of the
acetal to afford alcohol 9 in good yield.16 After Swern oxidation of 9,
the resulting aldehyde was subjected to Wittig reaction to give the
olefin 10. Asymmetric dihydroxylation of 10 with AD mix-b yielded
diol 11, which on selective tosylation17 and subsequent treatment
with K2CO3 afforded epoxide 5 as a diastereomeric mixture.
The dithiane 6, a counter-part of 5, was synthesized from the
known alcohol 8 (Scheme 6). After acetylation of 8, exhaustive
hydrogenolysis gave alcohol 12, which on Swern oxidation and
subsequent thioacetalization afforded dithiane 13. Conversion of an
acetyl group to a TES group in two steps gave the dithiane 6, which
was subjected to the next coupling reaction.
* Corresponding author. Tel./fax: þ81 45 566 1717.
E-mail address: nisiyama@chem.keio.ac.jp (S. Nishiyama).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.078

9496
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
OH
OH
OH
OH
OH
OH
OH
HO
O
O
OH
HO
O
O
H
HO
O
O
H
O
O
OH
O
O
O
H
O
H
OH
O
OH
O
OH
OH
O
O
OH
OH
O
O
O
O
O
HO
Me2N
HO
HO
HO
Me2N
OMe
H
H
Dunaimycin D2S
As published,
without stereochemistry
Cytovaricin
Ossamycin
R3
O
R1 R2 R3 R4 R5
OH
OH
OH
HO
O
H
CH2
O
CH2
O
Oligomycin A Me
Oligomycin B Me
H
H
H
OH
OH
H
Me
Me
Me
Me
Et
OH
O
O
O
OH
O
H
O
Oligomycin C
Me
OH
O
H
O
Oligomycin E Me
Oligomycin F Me
OH OH
O
Et
O
OH
OH CH2
H
H
H
R2
O
R4
Me2N
OH
R1
Rutamycin A
Rutamycin B
CH2
Me
CH2 Me
H
H
OH
H
O
OH
R5
H
A82548A
Figure 1. Macrolide antibiotics.
33
OTBS
esterification
OH
OH
OH
O
1
HO
O
1
O
O
O
O
23
OH
O
H
HO
OMe
OBn
O
8
O
OH
OH
O
S
O
BnO
O
H
O
H
Me2N
O
OAc
HO
Me2N
S
HO
17
17
OTBDPS
16
glycosylation
H
16
L-ossamine
OTES
spiroketal subunit
RCM
Ossamycin
polyol subunit
Scheme 1. Retrosynthetic analysis of ossamycin.
33
toxicity
O
HgCl2
or
R1
R2
OH
S
S
33
R1
OTBS
R2
OH
n
m
n
m
MeI
or
OH
O
OH
HO
OTBS
+
NBS
etc.
O
S
O
S
S
TESO
H
n
17
O
R2
acid condition
S
O
17
R1
O
20
OTES
OTs
m
OTES
spiroketal subunit
Scheme 2. Retrosynthetic analysis of the spiroketal subunit.
1
2
Scheme 3. Construction of spiroketal through the dithiane intermediate.
With hydroxy-thioacetal 4 in hand, we initiated construction of
a spiroacetal moiety (Table 1). First, we synthesized the spiroacetal
moiety 3 utilizing chemical reagents (Table 1, entries 1–5). Removal
of the dithiane group in 4 with MeI led to the desired spiroacetal 3,
although the yield was relatively low (entry 1). The stereostructure
of spiroacetal 3 was determined by the NOE technique (Fig. 2).
Using HgCl2 in the presence of CaCO3, the undesired spiroacetal 30
was co-produced (entry 2). In contrast, reactions with HgCl2 and
NBS (entries 3 and 4) gave the desired spiroacetal framework in
Synthesis of hydroxy-thioacetal 4, a precursor of the spiroacetal
framework, is shown in Scheme 7. Coupling of epoxide 5 with
dithiane 6 proceeded smoothly to give the desired compound 14.
After acetylation of the secondary alcohol and selective depro-
tection of the TES group of 14, the resulting alcohol 15 underwent
deprotection of the p-methoxybenzyl group with DDQ to afford
a mixture of diol 4 and its minor diastereomer 40.

E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
9497
OTBDPS
HO
AcO
OH
O
S
S
AcO
OTBDPS
BnO
O
3
4
OBn
OH
OPMB
OBn
O
OBn
HO
5
7
OH
OTES
S
S
BnO
OTBDPS
OTBDPS
6
8
Scheme 4. Retrosynthetic analysis of spiroketal 3.
the solvent MeOH to give methylacetals 16 and 160. To prevent the
undesired solvent attack, changing the solvent from MeOH to
MeCN markedly improved the yield (entry 7). 2,2,2-Tri-
fluoroethanol (TFE), which is known to possess a wide potential
window and low nucleophilicity, also gave similar results, and no
byproducts were detected (entry 8). On the other hand, use of
nBu4NBr as a source of bromonium ion afforded no desired reaction
product (entry 9). We also examined the effects of the hypervalent
iodine reagent generated by anodic oxidation of iodobenzene.18 The
oxidant, in situ produced, improved the yield of 3 up to 87%, which
was similar to that of PIFA (entry 10).
OPMB
OPMB
OBn
OH
a, b
c, d
OBn
OBn
HO
e
HO
7
9
10
OH
OPMB
OH OPMB
OBn
OPMB
f, g
O
OBn
HO
OBn HO
11
5
2.4:1
Scheme 5. Reagents and conditions: (a) p-anisaldehyde dimethylacetal, CSA, CH2Cl2; (b)
BH3$SMe2, toluene, 89% in 2 steps; (c) (COCl)2, DMSO, Et3N, CH2Cl2; (d) Ph3PþMeBrꢀ,
nBuLi, THF, 86% in 2 steps; (e) AD mix- , MeSO2NH2, tBuOH–H2O (1:1), 99% (ca. 2.4:1
b
mixture); (f) nBu2SnO, TsCl, Et3N, CH2Cl2; (g) K2CO3, MeOH, 83% in 2 steps.
2.2. Synthesis of 1
OAc
OH
a, b
e, f
c, d
With the successful production of 3, we turned our attention to
application to synthesis of the spiroacetal moiety (C20–C33) 1 of
ossamycin. Retrosynthesis of 1 (Scheme 8) indicated that the
hydroxy-thioacetal 17, a precursor of the spiroacetal, would be
synthesized by coupling of epoxide 5 and dithiane 18, which would
be prepared from (S)-malic acid.
BnO
S
OTBDPS
OTBDPS
OTBDPS
HO
8
12
S
OAc
S
OTES
OTBDPS
S
13
6
Based on the results of retrosynthetic analysis, the synthesis of
dithiane 18 was initiated by reduction of (S)-malic acid, followed by
selective protection of a 1,2-diol to provide alcohol 19 (Scheme 9).
After oxidation of 19, the resulting aldehyde was subjected to
allylation, to give the known alcohol 2019 and its diastereomer 200.
The undesired product 200 was converted to the desired product 20
by the Mitsunobu protocol. Although 20 was stereoselectively
produced using the Brown allyl(Ipc)2borane protocol,19 we selected
a simple two-step procedure to synthesize a large quantity of 20.
Deprotection of alcohol 20, followed by selective tosylation of the
primary alcohol gave tosylate 21 in good yield. The diol part of 21
was protected with TES groups, and methylation afforded olefin 22.
Scheme 6. Reagents and conditions: (a) Ac2O, Pyr.; (b) H2, 10% Pd–C, EtOAc, 73% in 2
steps; (c) (COCl)2, DMSO, Et3N, CH2Cl2; (d) 1,3-propanedithiol, BF3$Et2O, CH2Cl2, 81% in
2 steps; (e) K2CO3, MeOH; (f) TESCl, Imid., DMF, 74% in 2 steps.
good yields without any byproducts; PIFA also gave similar results
(entry 5). Subsequently, we examined removal of the dithiane
group utilizing electrochemical methodology (entries 6–10). Oxi-
dation was performed under CCE (constant current electrolysis)
conditions using a glassy carbon beaker as an anode, a platinum
wire as a cathode, and LiBr as a source of bromonium ion. Anodic
oxidation of dithiane 4 in MeOH as a solvent, produced the
expected spiroacetal 3 in low yield, due to reaction of products with
a
b, c
HO
OTES
OTBDPS
PMBO
BnO
S
OTES
OTBDPS
S
S
OPMB
OBn
O
S
6
14
5
HO
HO
AcO
OH
OH
S
S
S
OTBDPS
OTBDPS
BnO
PMBO
BnO
AcO
OH
4
S
S
d
OTBDPS
+
AcO
S
1 5
BnO
4'
n
Scheme 7. Reagents and conditions: (a) BuLi, THF, then 5, 94%; (b) Ac2O, DMAP, Pyr.; (c) AcOH, THF–H2O (13:2), 86% in 2 steps; (d) DDQ, CH2Cl2–H2O (13:2), 61% as 4, 32% as 40.

9498
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
Table 1
Construction of spiroketal structure
OTBDPS
O
OTBDPS
AcO
O
O
HO AcO
OH
AcO
S
S
Table 1
OTBDPS
BnO
3'
OBn
O
OMe
AcO
OH
OTBDPS
4
OTBDPS
3
OBn
O
OH OAc O
BnO
OBn
16+16'
OMe
Yields
16+16'
Entry
Reagents
Solvent
3
3'
4
1
2
3
4
5
MeI
HgCl2, CaCO3
HgCl2
MeCN aq.
MeCN aq.
MeCN aq.
Acetone aq.
CH2Cl2
30
26
77
88
88
28
60
9
general
methods
NBS
PIFA
6
LiBr
LiBr
LiBr
MeOH
MeCN
9
73
7**
8
92
89
electrochemical
methods*
CF3CH2OH
(CCE)
n
9
dec.
Bu4NBr
MeCN
10
PhI, LiClO4
CF3CH2OH
87
* anode: glassy carbon beaker, cathode: Pt wire, current: 0.3 mA/cm2.
** Lithium metal was depositedon the cathode.
treated with 2,2-dimethoxypropane in the presence of catalytic
CSA to afford the desired dithiane 18.
Me
O
OAc
5%
BnO
6%
H
Dithiane 18 was lithiated, and coupled with epoxide 5 to give
the corresponding alcohol 26 as a diastereomeric mixture, which
on acetylation and deprotection with a PMB group, yielded alcohol
27, along with its diastereomer 270 (Scheme 10). After chromato-
graphic separation, hydrolysis of 27 with PPTS in MeOH–H2O
effected deprotection of an isopropylidene group and provided the
hydroxy-thioacetal 17, a precursor of the spiroacetal framework.
Under the optimized conditions determined in the model study
discussed above, anodic oxidation of 17 afforded the desired spi-
roacetal 28 in almost quantitative yield. The stereochemistry of 28
was also confirmed by NOE experiments of the acetyl derivative 29.
Protection of 28 as a TBS ether, followed by hydrogenation and
tosylation afforded tosylate 31. Finally, exchange of an acetyl group
to a TES group smoothly afforded the spiroacetal moiety (C20–C33)
of ossamycin.
H
H
O
TBDPSO
NOE
3
Figure 2. NOE correlation of compound 3.
33
OTBS
O
OH OH
HO AcO
BnO
TESO
S
S
O
1
17
20
OTs
OPMB
O
3. Conclusion
OBn
In conclusion, we have synthesized the spiroacetal moiety (C20–
C33) of ossamycin. The spiroacetalization by anodic oxidation gave
the desired spiroacetal compound in excellent yield, without any
difficulties. Further studies toward total synthesis of ossamycin are
currently in progress in our laboratory.
5
OH
CO2H
S
O
O
HO2C
S
(S)-malic acid
18
Scheme 8. Retrosynthetic analysis of spiroketal 1.
4. Experimental section
4.1. General procedures
After oxidative cleavage of the olefin part of 22, the resulting al-
dehyde was subsequently subjected to Wittig reaction, hydroge-
nation, and then DIBAL-reduction to give alcohol 24. Oxidation of
24 and subsequent thioacetalization provided diol 25, which was
IR spectra were recorded on a JASCO Model A-202 spectropho-
tometer. 1H NMR and 13C NMR spectra were obtained on JEOL JNM

E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
9499
OH
CO2H
(S)-malic acid
O
a-c
d, e
OH
OH
O
O
+
HO2C
O
O
O
HO
19
20
20'
f, g
OH OH
TESO
OTES
TESO
OTES
h, i
j, k
l-n
20
OTs
MeO2C
21
22
23
S
S
O
O
TESO
OTES
S
OH OH
o, p
q, r
s
HO
S
24
25
18
Scheme 9. Reagents and conditions: (a) BH3$SMe2, B(OMe)3, THF; (b) CSA, CuSO4, 2,2-dimethoxypropane; (c) CSA, 3-pentanone, 100 ꢁC, 75% in 3 steps; (d) NCS, K2CO3, PhSNHtBu,
MS 4 Å, CH2Cl2; (e) allylmagnesium bromide, Et2O, 20: 29% in 2 steps, 200: 33% in 2 steps; (f) DEAD, p-nitrobenzoic acid, PPh3, PhMe; (g) 1 M KOH, MeOH, 77% in 2 steps; (h) 1 M HCl,
MeOH; (i) nBu2SnO, TsCl, Et3N, CH2Cl2, 93% in 2 steps; (j) TESCl, Imid., DMF; (k) MeLi, CuCN, Et2O, 81% in 2 steps; (l) OsO4, NMO, tBuOH-H2O (1:1); (m) NaIO4, 2,6-lutidine, THF–H2O
(4:1); (n) Ph3P]CHCO2Me, PhMe, 86% in 3 steps; (o) 10% Pd–C, H2, EtOAc; (p) DIBAL, CH2Cl2, 88% in 2 steps; (q) TEMPO, BAIB, CH2Cl2; (r) BF3$OEt2, 1,3-propanedithiol, CH2Cl2, 93% in
2 steps; (s) CSA, 2,2-dimethoxypropane, 100%.
b, c
a
HO
O
O
PMBO
BnO
S
O
O
S
S
OPMB
O
S
OBn
18
26
5
HO AcO
O
O
AcO
O
O
HO
S
S
S
S
BnO
+
BnO
27
27'
OR
AcO
HO
OH OH
d
e
O
g
S
S
AcO
27
BnO
O
17
28: R = H
f
OBn
29: R = Ac
Me
10%
BnO
7%
AcO
OAc
OTBS
OTBS
O
OTBS
H
O
O
O
AcO
AcO
h, i
j, k
H
O
O
TESO
H
O
4%
O
H
OBn
OTs
OTs
30
31
NOE
1
29
Scheme 10. Reagents and conditions: (a) nBuLi, THF, 65 ꢁC, 81%; (b) Ac2O, DMAP, Pyr.; (c) DDQ, CH2Cl2–H2O (4:1), 27: 61% in 2 steps, 270: 32% in 2 steps; (d) PPTS, MeOH–H2O (5:1),
99%; (e) CCE, 1.7 F/mol, LiBr, TFE, 99%; (f) Ac2O, Pyr., 100%; (g) TBSOTf, 2,6-lutidine, CH2Cl2, 89%; (h) 10% Pd–C, H2, MeOH; (i) TsCl, DMAP, Pyr., 50 ꢁC, 92% in 2 steps; (j) K2CO3, MeOH;
(k) TESCl, Imid., DMF, 91% in 2 steps.
EX-270 and JEOL JNM GX-400 spectrometers in a deuteriochloro-
form (CDCl3) solution using tetramethylsilane as an internal stan-
dard. Optical rotations were recorded on a JASCO P-2200 digital
polarimeter. High-resolution mass spectra were obtained on JEOL
JMS-700 (FAB) or Waters LCT Premier XE (ESI). Preparative and
analytical TLCs were carried out on silica gel plates (Kieselgel 60
F254, E. Merck AG, Germany) using UV light and/or 5% phospho-
molybdic acid in ethanol for detection. Kanto Chemical silica 60N
purchased from Kanto Chemical Co., Inc. Other anhydrous solvents
were also obtained through activated commercially available alu-
mina column, and stored over MS 4 Å under an argon atmosphere.
4.2. (2S,3R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-
2-methylbutan-1-ol (9)
A mixture of 7 (2.10 g, 10 mmol) and p-anisaldehyde dimethyl-
acetal (1.87 mL, 11 mmol) in CH2Cl2 (20 mL) in the presence of
catalytic amounts of CSA was stirred at room temperature for 17 h.
The reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers
(spherical, neutral, 63–210 mm) was used for column chromato-
graphy. All reactions were carried out under an argon atmosphere,
unless otherwise noted. When necessary, solvents were dried prior
to use. Dry tetrahydrofuran (THF) and dry diethyl ether (Et2O) were

9500
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
were washed with brine, dried (Na2SO4), and then evaporated. The
residue was purified by silica gel column chromatography (PhH to
4.4. (2R,3S,4R)-5-(Benzyloxy)-4-(4-methoxybenzyloxy)-
3-methylpentane-1,2-diol (11)
hexane/EtOAc 25/1) to give an acetal (3.29 g, 100%) as a colorless
19
oil: [
a
]
þ9.4 (c 1.00, CHCl3); IR (film) 2962, 2910, 2856, 1616, 1518,
A mixture of 10 (40 mg, 0.12 mmol), AD mix-b (346 mg), and
D
1248, 1113 cmꢀ1; 1H NMR
d
1.15 (3H, d, J¼6.8 Hz), 1.70 (1H, m), 3.48
MeSO2NH2 (35 mg, 0.37 mmol) in tBuOH (0.6 mL)–H2O (0.6 mL)
was stirred at 0 ꢁC for 24 h. The reaction was quenched by the
addition of saturated aq Na2SO3, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
silica gel column chromatography (hexane/EtOAc 1/2) to give 11
(44 mg, 99%) as a ca. 2.4:1 diastereomeric mixture: IR (film) 3410,
(1H, dd, J¼5.9, 9.8 Hz), 3.59 (1H, m), 3.77 (3H, s), 3.98 (1H, d,
J¼11.2 Hz), 4.07 (1H, dd, J¼2.4, 11.2 Hz), 4.21 (1H, dt, J¼2.4, 6.3 Hz),
4.50 (1H, d, J¼11.7 Hz), 4.61 (1H, d, J¼11.7 Hz), 5.48 (1H, s), 6.87 (2H,
complex), 7.26–7.34 (5H, complex), 7.41 (2H, complex); 13C NMR
11.2, 30.0, 55.2, 70.6, 73.4, 73.6, 78.3, 101.6, 113.5, 127.3, 127.55,
127.63, 128.3, 131.1, 138.0, 159.8. Anal. Calcd for C20H24O4: C, 73.15;
H, 7.37%. Found: C, 73.16; H, 7.40%.
d
2931, 2873, 1612, 1513, 1248, 1072, 1036 cmꢀ1; 1H NMR
d 0.87–0.93
A mixture of the acetal (660 mg, 2.0 mmol) and BH3$SMe2
(2.0 M solution in THF, 3.0 mL, 6.0 mmol) in PhMe (6 mL) was
stirred at 110 ꢁC for 0.5 h. The reaction was quenched by the ad-
dition of H2O, and the resulting mixture was extracted with EtOAc.
The organic layers were washed with brine, dried (Na2SO4), and
then evaporated. The residue was purified by silica gel column
(3H, complex), 3.56–3.75 (4H, complex), 3.80 (3H, s), 3.85–3.90 (1H,
m), 4.45–4.70 (4H, complex), 6.85–6.88 (2H, complex), 7.21–7.33
(7H, complex).
4.5. (R)-2-[(2S,3R)-4-(Benzyloxy)-3-(4-methoxybenzyloxy)-
butan-2-yl]oxirane (5)
chromatography (hexane/EtOAc 5/1) to give 9 (588 mg, 89%) and 7
20
(25.4 mg, 6%) as a colorless oil. 9: [
a]
þ28.7 (c 1.00, CHCl3); IR
A mixture of 11 (251 mg, 0.69 mmol), Bu2SnO (52 mg,
D
(film) 3433, 2873, 1612, 1514, 1248, 1086, 1036 cmꢀ1; 1H NMR
d
0.92
0.21 mmol), TsCl (146 mg, 0.77 mmol), and Et3N (0.11 mL,
0.79 mmol) was stirred at 0 ꢁC for 30 min; the mixture was allowed
to warm to room temperature. After being stirred at the same
temperature for 5 h, the reaction was quenched by the addition of
H2O, and the resulting mixture was extracted with EtOAc. The or-
ganic layers were washed with brine, dried (Na2SO4), and then
evaporated. The residue was purified by silica gel column chro-
matography (hexane/EtOAc 2/1) to give a tosylate (358 mg): IR
(film) 3427, 2933, 1612, 1514, 1360, 1248, 1176, 1095, 1034 cmꢀ1; 1H
(3H, d, J¼6.8 Hz), 1.97 (1H, m), 2.31 (1H, br), 3.52–3.61 (3H, com-
plex), 3.65–3.72 (2H, complex), 3.79 (3H, s), 4.51 (1H, d, J¼11.2 Hz),
4.55 (2H, s), 4.65 (1H, d, J¼11.2 Hz), 6.86 (2H, d, J¼8.8 Hz), 7.24–7.37
(7H, complex); 13C NMR
d 11.9, 37.7, 55.2, 65.6, 70.9, 72.1, 73.4, 79.4,
113.7, 127.5, 127.6, 128.3, 129.4, 130.5, 137.9, 159.0. Anal. Calcd for
20H26O4: C, 72.70; H, 7.93%. Found: C, 72.55; H, 7.91%.
C
4.3. 1-{[(2R,3S)-1-(Benzyloxy)-3-methylpent-4-ene-
2-yloxy]methyl}-4-methoxy-benzene (10)
NMR d 1.98 (1H, m), 2.43 (3H, s), 2.93 (1H, m), 3.51 (0.3H, d,
J¼4.4 Hz), 3.54 (0.7H, d, J¼4.6 Hz), 3.62–3.78 (2H, complex), 3.80
(3H, s), 3.87–4.13 (3H, complex), 4.40–4.53 (3H, complex), 4.60
(0.7H, d, J¼4.8 Hz), 4.64 (0.3H, d, J¼4.8 Hz), 6.85 (2H, d, J¼8.6 Hz),
7.17–7.21 (2H, complex), 7.29–7.36 (7H, complex), 7.75–7.79 (2H,
complex).
A mixture of the tosylate (358 mg, 0.70 mmol) and K2CO3
(289 mg, 2.1 mmol) in MeOH (7 mL) was stirred at 0 ꢁC for 30 min.
The reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers
were washed with brine, dried (Na2SO4), and then evaporated. The
residue was purified by silica gel column chromatography (hexane/
EtOAc 7/1) to give 5 (199 mg, 83% in 2 steps) as a ca. 2.4:1 dia-
stereomixture: IR (film) 2864, 2360, 1612, 1514, 1248, 1088,
1036 cmꢀ1. Anal. Calcd for C21H26O4: C, 73.66; H, 7.65%. Found: C,
73.30; H, 7.58%.
To a solution of (COCl)2 (0.13 mL, 1.6 mmol) in CH2Cl2 (1.5 mL)
was added DMSO (0.14 mL, 1.93 mmol) in CH2Cl2 (1 mL) at ꢀ78 ꢁC.
The mixture was stirred for 15 min, and then a solution of 9
(128 mg, 0.39 mmol) in CH2Cl2 (1.5 mL) was slowly added. After
being stirred at ꢀ40 ꢁC for 30 min, Et3N (0.55 mL, 3.9 mmol) was
added at ꢀ78 ꢁC, and then the mixture was allowed to warm to
room temperature. After being stirred for 30 min, the reaction
mixture was extracted with EtOAc. The organic layers were washed
with 1 M aq HCl and brine, dried (Na2SO4), and then evaporated.
The residue was purified by silica gel column chromatography
(hexane/EtOAc 4/1) to give an aldehyde (120 mg): 1H NMR
d 1.10
(3H, d, J¼7.1 Hz), 2.65 (1H, m), 3.54 (1H, dd, J¼5.6, 10 Hz), 3.63 (1H,
dd, J¼5,10 Hz), 3.80 (3H, s), 3.99 (1H, dd, J¼5.0,10.1 Hz), 4.48 (1H, d,
J¼11.5 Hz), 4.52 (2H, s), 4.58 (1H, d, J¼11.5 Hz), 6.86 (2H, d,
J¼8.7 Hz), 7.22 (2H, d, J¼8.7 Hz), 7.29–7.38 (5H, complex), 9.69 (1H,
d, J¼0.8 Hz).
4.6. (R)-1-(tert-Butyldiphenylsilyloxy)-6-hydroxyhexan-
2-yl ethanoate (12)
To a suspension of [Ph3PMe]þBrꢀ (415 mg, 1.2 mmol) in THF
(1.5 mL) was added nBuLi (1.58 M solution in hexane, 0.69 mL,
1.1 mmol) at 0 ꢁC, and then stirred for 2 h. A solution of the al-
dehyde (120 mg, 0.36 mmol) in THF (2.1 mL) was added at ꢀ45 ꢁC.
After being stirred at room temperature for 16 h, the reaction was
quenched by the addition of H2O. The reaction mixture was
extracted with EtOAc, and the organic layers were washed with
brine, dried (Na2SO4), and then evaporated. The residue was pu-
A mixture of 8 (4.61 g, 10.1 mmol) and Ac2O (10 mL) in pyridine
(20 mL) was stirred at room temperature for 18 h. The reaction was
quenched by the addition of H2O, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with 1 M aq
HCl and brine, dried (Na2SO4), and then evaporated. The residue
was purified by silica gel chromatography (hexane/EtOAc 10/1) to
24
rified by silica gel column chromatography (hexane/EtOAc 1/1 and
give an ester (5.08 g, 100%): [
a]
þ0.97 (c 1.0, CHCl3); IR (film)
D
25
then hexane/EtOAc 20/1) to give 10 (109 mg, 86% in 2 steps): [
a
]
3070, 2931, 2857,1743,1428,1237,1113 cmꢀ1; 1H NMR
d 1.05 (9H, s),
D
þ2.01 (c 1.00, CHCl3); IR (film) 2864, 2360, 1612, 1514, 1248, 1090,
2.03 (3H, s), 2.64–2.70 (2H, complex), 3.82 (2H, complex), 4.11 (2H,
s), 4.54 (2H, s), 5.05 (1H, m), 7.28–7.44 (11H, complex), 7.66 (4H,
1038 cmꢀ1 1H NMR
;
d
1.04 (3H, d, J¼6.8 Hz), 2.48 (1H, m),
3.45 (1H, m), 3.52 (1H, m), 3.61 (1H, dd, J¼3.9, 10.3 Hz), 3.80 (3H,
s), 4.50 (1H, d, J¼11.2 Hz), 4.52 (2H, s), 4.66 (1H, d, J¼11.2 Hz),
4.97–5.06 (2H, complex), 5.80 (1H, m), 6.85 (2H, d, J¼8.6 Hz), 7.3
complex); 13C NMR
d 19.3, 20.9, 21.1, 26.8, 57.5, 63.7, 71.3, 72.2, 77.9,
82.1, 127.58, 127.60, 127.7, 127.9, 128.3, 129.62, 129.64, 133.0, 133.1,
135.39, 135.45, 137.4, 170.1. Anal. Calcd for C31H36O4Si: C, 74.36; H,
7.25%. Found: C, 74.10; H, 7.28%.
(7H, complex); 13C NMR
d 15.7, 40.0, 55.3, 71.6, 72.4, 73.3, 81.5,
113.6, 114.4, 127.4, 127.5, 128.2, 129.3, 131.0, 138.4, 140.9, 158.9.
Anal. Calcd for C21H26O3: C, 77.27; H, 8.03%. Found: C, 77.22; H,
8.08%.
A solution of the ester (172 mg, 0.34 mmol) in EtOAc (3.4 mL) in
the presence of catalytic amounts of 10% Pd–C was stirred at room
temperature for 21.5 h under
a hydrogen atmosphere. After

E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
9501
filtration, the filtrate was evaporated. The residue was purified by
12 mmol) at 0 ꢁC; the mixture was stirred for 1 h. The reaction was
quenched by the addition of H2O, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
silica gel column chromatography (hexane/EtOAc 4/1–2/1) to give
25
12 (103 mg, 73%): [
a]
þ17.4 (c 1.0, CHCl3); IR (film) 3447, 3071,
D
2931, 2858, 1740, 1428, 1240, 1113 cmꢀ1 1H NMR
; d 1.04 (9H, s),
1.26–1.41 (3H, complex), 1.50–1.67 (3H, complex), 2.03 (3H, s), 3.61
silica gel column chromatography (hexane/EtOAc 40/1) to give 6
23
(2H, t, J¼6.4 Hz), 3.68 (2H, m), 5.00 (1H, m), 7.35–7.43 (6H, com-
(1.22 g, 90%): [
a
]
þ9.8 (c 1.0, CHCl3); IR (film) 3070, 2952, 1461,
D
plex), 7.64–7.67 (4H, complex); 13C NMR
d
19.3, 21.3, 21.5, 26.8, 30.3,
1427, 1240, 1113, 1007 cmꢀ1
;
1H NMR
d
0.51 (6H, q, J¼7.8 Hz), 0.89
32.6, 62.7, 65.0, 74.2, 127.6, 129.57, 129.60, 133.26, 133.29, 135.4,
135.5,170.6. Anal. Calcd for C24H34O4Si: C, 69.52; H, 8.27%. Found: C,
69.22; H, 8.34%.
(9H, t, J¼7.8 Hz), 1.05 (9H, s), 1.40–1.63 (3H, complex), 1.68–1.80
(3H, complex), 1.82–1.95 (1H, m), 2.05–2.16 (1H, m), 2.83–2.88 (4H,
complex), 3.46 (1H, dd, J¼7, 10 Hz), 3.58 (1H, dd, J¼4.8, 10 Hz), 3.70
(1H, m), 4.04 (1H, t, J¼7 Hz), 7.40 (6H, complex), 7.67 (4H, com-
4.7. (R)-1-(tert-Butyldiphenylsilyloxy)-5-(1,3-dithian-
plex); 13C NMR
d 5.0, 7.0, 19.3, 22.2, 26.1, 26.9, 30.5, 33.9, 35.7, 47.5,
2-yl)pentan-2-yl ethanoate (13)
67.5, 72.4, 127.5, 129.5, 133.4, 135.47, 135.48.
To a solution of (COCl)2 (0.27 mL, 3.1 mmol) in CH2Cl2 (3.8 mL)
was added DMSO (0.28 mL, 3.9 mmol) in CH2Cl2 (1 mL) at ꢀ78 ꢁC;
the mixture was stirred for 20 min, and a solution of 12 (324 mg,
0.78 mmol) in CH2Cl2 (3 mL) was slowly added. After being stirred
at ꢀ40 ꢁC for 1 h, Et3N (1.1 mL, 7.9 mmol) was added at ꢀ78 ꢁC, and
the mixture was allowed to warm to room temperature. After being
stirred at the same temperature for 10 min, the reaction was
quenched by the addition of H2O, and then the mixture was
extracted with EtOAc. The organic layers were washed with 1 M aq
HCl and brine, dried (Na2SO4), and then evaporated. The residue
was purified by silica gel column chromatography (hexane/EtOAc
4.9. (3S,4R)-5-(Benzyloxy)-1-{2-[(R)-5-(tert-butyldi-
phenylsilyloxy)-4-(triethylsilyloxy)-pentyl]-
1,3-dithiane-2-yl}-4-(4-methoxybenzyloxy)-
3-methylpentan-2-ol (14)
To a solution of 6 (325 mg, 0.57 mmol) in THF (2 mL) was added
nBuLi (1.58 M solution in hexane, 0.30 mL, 0.47 mmol) at 0 ꢁC. After
being stirred for 15 min, 5 (151 mg, 0.44 mmol) in THF (2.4 mL) was
added at 0 ꢁC, and the mixture was stirred for 40 min. The reaction
was quenched by the addition of saturated aq NH4Cl, and the
resulting mixture was extracted with CHCl3. The organic layers
were dried (Na2SO4), and then evaporated. The residue was purified
by silica gel column chromatography (hexane/EtOAc 40/1–8/1) to
give 14 (378 mg, 94%) as a diastereomeric mixture: IR (film) 3482,
5/1) to give an aldehyde (294.2 mg): 1H NMR
d 1.04 (9H, s), 1.62–
1.83 (4H, complex), 2.00 (3H, s), 2.35–2.45 (2H, complex), 3.62–3.74
(2H, complex), 4.99 (1H, m), 7.35–7.45 (6H, complex), 7.63–7.67
(4H, complex), 9.73 (1H, t, J¼1.5 Hz).
2952, 2873, 1513, 1428, 1248, 1112 cmꢀ1 1H NMR
; d 0.47–0.55 (6H,
To a solution of the aldehyde (294 mg, 0.71 mmol) and 1,3-
propanedithiol (0.11 mL, 1.1 mmol) in CH2Cl2 (7 mL) was slowly
added BF3$OEt2 (0.9 mL, 0.71 mmol) at ꢀ40 ꢁC. After being stirred
for 20 min, the reaction was quenched by the addition of 1 M aq
KOH, and the resulting mixture was extracted with CHCl3. The or-
ganic layers were dried (Na2SO4), and then evaporated. The residue
complex), 0.88 (9H, t, J¼7.8 Hz), 0.90–0.99 (3H, complex), 1.04 (9H,
complex), 1.44–2.26 (9H, complex), 2.78–2.86 (4H, complex), 3.76–
3.77 (3H, complex), 3.31–3.80 (6H, complex), 4.06–4.16 (1H, m),
4.48–4.58 (3H, complex), 4.64–4.70 (1H, m), 6.82–6.85 (2H, com-
plex), 7.22–7.41 (13H, complex), 7.65–7.68 (4H, complex).
was purified by silica gel column chromatography (hexane/EtOAc
4.10. (3S,4R)-5-(Benzyloxy)-1-{2-[(R)-5-(tert-
butyldiphenylsilyloxy)-4-hydroxypentyl]-1,3-dithiane-2-yl}-
4-(4-methoxybenzyloxy)-3-methylpentan-2-yl ethanoate (15)
24
15/1) to give 13 (321 mg, 82% in 2 steps): [
a]
þ9.8 (c 1.0, CHCl3); IR
D
(film) 3070, 2931, 2856, 1738, 1427, 1240, 1112 cmꢀ1; 1H NMR
d 1.04
(9H, s), 1.43–1.66 (3H, complex), 1.69–1.83 (2H, complex), 1.86–1.93
(1H, m), 2.02 (3H, s), 2.08–2.15 (1H, m), 2.62–2.78 (1H, m), 2.83 (4H,
complex), 3.68 (2H, complex), 4.00 (1H, t, J¼6.7 Hz), 4.98 (1H, m),
A mixture of 14 (863 mg, 0.94 mmol) and Ac2O (3 mL) in pyridine
(6 mL) in the presence of catalytic amounts of DMAP was stirred at
0 ꢁC for 2 h. After the addition of H2O, the resulting mixture was
extracted with EtOAc. The organic layers were washed with 1 M aq
HCl, saturated aq NaHCO3, and brine, dried (Na2SO4), and then
evaporated. The residue was purified by silica gel chromatography
(hexane/EtOAc 8/1–4/1) to give an ester (804 mg, 89%) and 15
(53 mg, 7%) as a diastereomeric mixture. Ester: IR (film) 2953, 2874,
7.35–7.43 (6H, complex), 7.64–7.67 (4H, complex); 13C NMR
d 19.3,
21.2, 22.4, 26.0, 26.8, 30.0, 30.4, 35.3, 47.3, 64.8, 74.0, 127.6, 129.57,
129.59, 133.2, 133.3, 135.4, 135.5, 170.4. Anal. Calcd for
C
27H38O3S2Si: C, 64.50; H, 7.62%. Found: C, 64.47; H, 7.58%.
4.8. (R)-6-[3-(1,3-Dithiane-2-yl)propyl]-8,8-diethyl-2,2-
dimethyl-3,3-diphenyl-4,7-dioxa-3,8-disiladecane (6)
1737, 1514, 1428, 1242, 1112 cmꢀ1; 1H NMR
d
0.50 (6H, d, J¼8.0 Hz),
0.88 (9H, t, J¼8.0 Hz), 0.94–0.99 (3H, complex),1.04 (9H, s),1.42–1.51
(1H, m), 1.64–1.66 (1H, m), 1.77–1.88 (4H, complex), 1.94–1.97 (3H,
complex), 1.99–2.09 (1H, m), 2.19–2.23 (2H, complex), 2.69 (4H,
complex), 3.40–3.49 (1H, m), 3.53–3.70 (5H, complex), 3.77 (3H, s),
4.41–4.68 (4H, complex), 5.27 (1H, m), 6.83 (2H, d, J¼8.4 Hz), 7.28–
7.39 (13H, complex), 7.64–7.67 (4H, complex). 15: IR (film) 3481,
A mixture of 13 (554 mg, 1.1 mmol) and K2CO3 (198 mg,
1.4 mmol) in MeOH (20 mL) was stirred at 0 ꢁC for 27.5 h. The re-
action was quenched by the addition of H2O, and the resulting
mixture was extracted with EtOAc. The organic layers were washed
with brine, dried (Na2SO4), and then evaporated. The residue was
purified by silica gel column chromatography (hexane/EtOAc 15/1)
3070, 2931, 2858,1733,1514,1428,1244,1112 cmꢀ1; 1H NMR
d 0.94–
24
to give alcohol (416 mg, 82%): [
a
]
D
ꢀ0.1 (c 1.0, CHCl3); IR (film)
0.99 (3H, complex), 1.06 (9H, s), 1.37–1.68 (3H, complex), 1.84–1.91
(4H, complex), 1.95–1.97 (3H, complex), 2.18–2.29 (2H, complex),
2.48 (1H, m), 2.68–2.70 (4H, complex), 3.44–3.50 (1H, m), 3.59–3.68
(5H, complex), 3.77 (3H, s), 4.45–4.68 (4H, complex), 5.27 (1H, m),
6.83 (2H, d, J¼8.4 Hz), 7.28–7.41 (13H, complex), 7.63–7.66 (4H,
complex). Anal. Calcd for C54H78O7S2Si2: C, 68.21; H, 7.59; S, 7.63%.
Found: C, 68.48; H, 7.50; S, 7.82%.
3465, 3070, 2931, 2858, 1427, 1113 cmꢀ1 1H NMR
; d 1.06 (9H, s),
1.34–1.51 (3H, complex), 1.54–1.66 (1H, m), 1.71–1.79 (2H, com-
plex), 1.81–1.91 (1H, m), 2.08–2.17 (1H, m), 2.48 (1H, d, J¼3.0 Hz),
2.82–2.91 (4H, complex), 3.48 (1H, dd, J¼7.3, 10 Hz), 3.64–3.98 (3H,
complex), 4.00 (1H, t, J¼6.8 Hz), 7.36–7.47 (6H, complex), 7.64–7.67
(4H, complex); 13C NMR
d 19.3, 22.8, 26.1, 26.9, 30.5, 32.3, 35.4, 47.4,
67.9, 71.6, 127.7, 129.7, 132.99, 133.01, 135.38, 135.41. Anal. Calcd for
To a solution of the ester (147 mg, 0.15 mmol) in THF (1.3 mL)–
H2O (0.2 mL) was added AcOH (1 mL) at 0 ꢁC. After being stirred at
0 ꢁC for 6.5 h, the reaction mixture was extracted with EtOAc. The
organic layers were washed with saturated aq NaHCO3 and brine,
C
25H36O2S2Si: C, 65.17; H, 7.88%. Found: C, 64.98; H, 7.88%.
To a solution of the alcohol (1.08 g, 2.4 mmol) in DMF (10 mL)
were added TESCl (0.8 mL, 4 mmol), and imidazole (800 mg,

9502
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
dried (Na2SO4), and then evaporated. The residue was purified by
silica gel column chromatography (hexane/EtOAc 4/1–8/1) to give
15 (125 mg, 97%) as a diastereomeric mixture.
4.54 (1H, d, J¼12.2 Hz), 4.61 (1H, d, J¼12.2 Hz), 5.32 (1H, dt, J¼5.1,
12.2 Hz), 7.31–7.40 (11H, complex), 7.67–7.71 (4H, complex); 13C
NMR d 5.2, 18.6, 19.3, 21.3, 26.6, 26.8, 33.0, 34.7, 35.8, 67.1, 68.9, 70.3,
70.7, 73.1, 97.4, 127.3, 127.51, 127.54, 127.6, 128.2, 129.4, 129.6, 133.6,
134.7, 135.6, 138.4, 170.0. Anal. Calcd for C37H48O6Si: C, 72.04; H,
7.84%. Found: C, 72.16; H, 7.96%.
4.11. (2S,3S,4R)-5-(Benzyloxy)-1-{2-[(R)-5-(tert-
butyldiphenylsilyloxy)-4-hydroxypentyl]-1,3-dithiane-2-yl}-
4-hydroxy-3-methylpentan-2-yl ethanoate (4) and (2R,3S,4R)-
5-(benzyloxy)-1-{2-[(R)-5-(tert-butyldiphenylsilyloxy)-
4-hydroxypentyl]-1,3-dithiane-2-yl}-4-hydroxy-
3-methylpentan-2-yl ethanoate (40)
Method B (Table 1, entry 2): A mixture of 4 (19 mg, 26 mmol),
HgCl2 (28 mg, 0.1 mmol), and CaCO3 (16 mg, 0.16 mmol) in MeCN
(0.4 mL)–H2O (0.1 mL) was stirred at room temperature for 4 days.
The reaction was quenched by the addition of saturated aq NaHCO3,
and the resulting mixture was extracted with EtOAc. The organic
layers were washed with brine, dried (Na2SO4), and then evapo-
rated. The residue was purified by PTLC (hexane/EtOAc 5/1) to give
3 (4.2 mg, 26%), 30 (1.4 mg, 9%), and 4 (11.3 mg, 60%). 30: 1H NMR
A mixture of 15 (393 mg, 0.47 mmol) and DDQ (127 mg,
0.56 mmol) in CH2Cl2 (4 mL)–H2O (0.4 mL) was stirred at 0 ꢁC for
1.5 h. After filtration, the filtrate was extracted with CHCl3. The or-
ganic layerswerewashedwithsaturatedaq NaHCO3, dried (Na2SO4),
and then evaporated. The residue was purified by silica gel column
d
0.86 (3H, d, J¼6.9 Hz), 1.04 (9H, s), 1.23–1.29 (2H, complex), 1.50–
1.61 (2H, complex), 1.80 (2H, complex), 1.97 (1H, m), 2.06 (3H, s),
2.15–2.21 (2H, complex), 3.41 (1H, dd, J¼6.7, 9.6 Hz), 3.47 (1H, dd,
J¼6.0, 9.6 Hz), 3.60 (1H, dd, J¼10, 10.7 Hz), 3.74–3.86 (3H, complex),
4.53 (1H, d, J¼11.9 Hz), 4.60 (1H, d, J¼11.9 Hz), 4.95 (1H, dt, J¼4.8,
12.5 Hz), 7.29–7.40 (11H, complex), 7.62–7.65 (4H, complex).
chromatography (hexane/EtOAc 3/1) to give 4 (207 mg, 61%) and 40
23
(107 mg, 32%). 4: [
a
]
D
ꢀ0.04 (c 1.0, CHCl3); IR (film) 3479, 3070,
2929, 2858, 1732, 1427, 1242, 1113 cmꢀ1 1H NMR
; d 0.93 (3H, d,
J¼6.9 Hz), 1.06 (9H, s), 1.38–1.62 (2H, complex), 1.78–1.94 (5H,
complex), 2.02 (3H, s), 2.20 (1H, dd, J¼8.7, 15.5 Hz), 2.36 (1H, d,
J¼15.5 Hz), 2.52 (1H, br), 2.78 (5H, complex), 3.44–3.53 (3H, com-
plex), 3.63 (1H, dd, J¼3.4, 10.0 Hz), 3.72 (1H, m), 3.84 (1H, m), 4.51
(1H, d, J¼11.9 Hz), 4.59 (1H, d, J¼11.9 Hz), 5.09 (1H, t, J¼7.2 Hz), 7.28–
Method C (Table 1, entry 3): A mixture of 4 (14 mg, 19 mmol) and
HgCl2 (31 mg, 0.11 mmol) in MeCN (0.2 mL)–H2O (0.05 mL) was
stirred at 0 ꢁC for 3.5 h. The reaction was quenched by the addition
of saturated aq NaHCO3, and the resulting mixture was extracted
with EtOAc. The organic layers were washed with brine, dried
(Na2SO4), and then evaporated. The residue was purified by PTLC
(hexane/EtOAc 5/1) to give 3 (9.1 mg, 77%).
7.44 (11H, complex), 7.64–7.67 (4H, complex); 13C NMR
d 8.7, 19.3,
20.5, 21.7, 25.1, 26.1, 26.3, 26.9, 32.9, 39.2, 39.4, 49.9, 52.3, 68.0, 69.3,
71.7, 72.6, 73.9, 127.6, 127.7, 128.3, 129.7, 132.9, 133.0, 135.38, 135.41,
137.8,171.2. Anal. Calcd for C40H56O6S2Si$0.5H2O: C, 65.44; H, 7.83; S,
Method D (Table 1, entry 4): A mixture of 4 (7.2 mg, 9.9
mmol)
23
8.73%. Found: C, 65.73; H, 7.60; S, 8.99%. 40: [
a
]
þ0.12 (c 1.0, CHCl3);
and NBS (12 mg, 70 mol) in acetone (0.2 mL)–H2O (0.02 mL) was
m
D
IR (film) 3464, 3070, 2931, 2858, 1732, 1427, 1240, 1113 cmꢀ1
NMR
;
1H
stirred at ꢀ20 ꢁC for 2.5 h. The reaction was quenched by the
addition of saturated aq Na2SO3, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
PTLC (hexane/EtOAc 5/1) to give 3 (5.4 mg, 88%).
d
0.98 (3H, d, J¼7.1 Hz), 1.06 (9H, s), 1.34–1.61 (2H, complex),
1.79–1.97 (5H, complex), 2.00 (3H, s), 2.21 (1H, dd, J¼2.1, 15.7 Hz),
2.29 (1H, dd, J¼7.9, 15.7 Hz), 2.44 (1H, br), 2.55 (1H, br), 2.77 (4H,
complex), 3.47 (2H, dd, J¼7.6,10 Hz), 3.54 (1H, dd, J¼3.8,10 Hz), 3.63
(1H, dd, J¼3.4, 10 Hz), 3.74 (1H, m), 3.87 (1H, m), 4.54 (2H, s), 5.23
(1H, m), 7.29–7.42 (11H, complex), 7.64–7.67 (4H, complex); 13C
Method E (Table 1, entry 5): A mixture of 4 (10 mg, 14
mmol) and
PIFA (12 mg, 28 mol) in CH2Cl2 (1 mL) was stirred at room tem-
m
NMR
d
9.7, 19.3, 20.3, 21.7, 25.2, 26.2, 26.9, 32.7, 38.4, 39.7, 40.3, 52.1,
perature for 30 min. The reaction was quenched by the addition of
H2O, and the resulting mixture was extracted with EtOAc. The
organic layers were washed with brine, dried (Na2SO4), and then
evaporated. The residue was purified by PTLC (hexane/EtOAc 5/1) to
give 3 (7.5 mg, 88%).
68.1, 70.2, 71.4, 72.3, 73.1, 73.3, 127.6, 127.7, 128.3, 129.70, 129.71,
132.96, 132.98, 133.0, 135.39, 135.41, 137.8, 171.2. HRMS (FAB) Calcd
for C40H56O6S2SiNa [MþNa]þ: 747.3185. Found: m/z 747.3176.
4.12. (2S,3S,4R,6R,8R)-2-(Benzyloxymethyl)-8-[(tert-
butyldiphenylsilyloxy)methyl]-3-methyl-1,7-
4.13. General procedure of anodic oxidation
dioxaspiro[5.5]undecan-4yl ethanoate (3), (2S,3S,4R)-
5-(benzyloxy)-1-{2-[(R)-5-(tert-butyldiphenylsilyloxy)-
4-hydroxypentyl]-1,3-dithiane-2-yl}-4-hydroxy-
All anodic oxidations were conducted using HA-301 galvanostat
(Hokuto Denko), a glassy carbon beaker as an anode, a platinum
wire as a cathode, and a standard calomel electrode as a reference
electrode. A solution of 4 in a solvent containing LiBr or nBu4NBr
was electrolyzed. Work up procedure: a reaction mixture was
partitioned between EtOAc and H2O. The organic layers were
washed with brine, dried (Na2SO4), and then evaporated to give
a crude product, which was purified by PTLC.
3-methylpentan-2-yl ethanoate (30), (4S,5S,6R)-
6-(benzyloxymethyl)-2-[(R)-5-(tert-butyldiphenylsiloxy)-
4-hydroxypentyl]-2-methoxy-5-methyltetrahydro-2H-pyran-
4-yl ethanoate (16), and (2S,3R,4S)-5-(benzyloxy)-1-[(6R)-6-
(tert-butyldiphenylsiloxy)methyl]-2-methoxyltetrahydro-2H-
pyran-2-yl-3-hydroxy-4-methylpentan-2-yl ethanoate (160)
Method F (Table 1, entry 10): A mixture of PhI (0.011 mL,
Method A (Table 1, entry 1): A mixture of 4 (13 mg, 0.18 mmol)
and MeI (0.011 mL, 0.18 mmol) in MeCN (0.2 mL)–H2O (0.05 mL)
was stirred at room temperature for 26 h. The reaction was
quenched by the addition of H2O, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
95 mmol) in TFE (10 mL) in the presence of LiClO4 (53 mg) was
electrolyzed (anode: glassy carbon beaker, cathode: Pt wire, cur-
rent: 0.5 mA/cm2, 3.0 F/mol, C. C. E.¼constant current electrolysis).
To this solution was added 4 (11.5 mg, 17 mmol) in TFE (1.5 mL).
After being stirred for 30 min., the reaction mixture was extracted
with EtOAc, and the organic layers were washed with brine, dried
(Na2SO4), and then evaporated. The residue was purified by PTLC
(hexane/EtOAc 5/1) to give 3 (8.5 mg, 87%).
PTLC (hexane/EtOAc 5/1) to give 3 (3.3 mg, 30%) and 4 (3.6 mg,
20
28%). 3: [
a
]
ꢀ28.8 (c 1.0, CHCl3); IR (film) 3070, 2931, 2857, 1743,
D
1427, 1365, 1244, 1113 cmꢀ1
;
1H NMR
d
0.82 (3H, d, J¼6.8 Hz), 1.06
(9H, s), 1.20–1.31 (1H, m), 1.42 (1H, dt, J¼4.1 13 Hz), 1.58–1.67 (4H,
complex), 1.78 (1H, dd, J¼4.9, 13 Hz), 1.86–1.96 (1H, m), 2.02 (3H, s),
2.17–2.20 (1H, m), 3.46 (1H, dd, J¼5.4, 10.3 Hz), 3.52–3.58 (2H,
complex), 3.66 (1H, dd, J¼5.4, 10.3 Hz), 3.85 (1H, m), 4.15 (1H, m),
4.14. 2-[(4S)-2,2-Diethyl-[1,3]dioxolan-4-yl]-ethanol (19)
To a solution of
L-malic acid (7.66 g, 57 mmol) in THF (30 mL)
was added BH3$SMe2 complex (2.0 M solution in THF, 100 mL,

E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
9503
200 mmol) and B(OMe)3 (22.2 mL, 200 mmol) at 0 ꢁC. After being
stirred at room temperature for 24 h, the reaction was quenched by
the addition of MeOH and concentrated in vacuo. The residue was
dissolved in 2,2-dimethoxypropane (80 mL), and CSA (2.3 g,
9.9 mmol) and CuSO4 (4.8 g, 27 mmol) were added at 0 ꢁC. After
being stirred at room temperature for 16 h, the reaction was
quenched by the addition of NaHCO3, and filtered. The filtrate was
concentrated in vacuo and the residue was purified by silica gel
column chromatography (hexane/EtOAc 1/2) to give a crude ace-
To a mixture of Ph3P (562 mg, 2.1 mmol) and p-nitrobenzoic acid
(358 mg, 2.1 mmol) in PhMe (10 mL) was added a solution of 200
(353 mg, 1.7 mmol) in PhMe (3 mL) at ꢀ30 ꢁC. To this mixture was
added DEAD (2.7 M solution in PhMe, 0.8 mL, 2 mmol) at the same
temperature, and the mixture was stirred for 3 h. The reaction was
quenched by the addition of saturated aq NaHCO3, and the organic
layerswerewashedwithbrine, dried(Na2SO4), and then evaporated.
The residue was dissolved in 1 M KOH/MeOH (10 mL), stirred at
room temperature for 16 h. The reaction was quenched by the ad-
dition of saturated aq NH4Cl, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
silica gel column chromatography (benzene/Et2O 15/1) to give 20
(271 mg, 77% in 2 steps).
tonide: 1H NMR
d
1.97 (3H, s), 1.43 (3H, s), 1.83 (2H, dt, J¼5.6,
6.0 Hz), 2.14 (1H, br), 3.60 (1H, t, J¼7.7 Hz), 3.81 (2H, t, J¼5.7 Hz),
4.09 (1H, dd, J¼6.2, 7.8 Hz), 4.28 (1H, m).
A mixture of the crude product and CSA (2.30 g, 9.9 mmol) in 3-
pentanone (50 mL) in the presence of Drierite was stirred at 100 ꢁC
for 26 h. The reaction was quenched by the addition of NaHCO3, and
filtered. The filtrate was concentrated in vacuo and the residue was
purified by silica gel column chromatography (hexane/EtOAc 4/1)
to give 19 (7.42 g, 75% in 3 steps) and the unreacted acetal (0.65 g,
4.16. (2S,4R)-1-Tosyloxy-hept-6-ene-2,4-diol (21)
To a solution of 20 (4.91 g, 23 mmol) in MeOH (20 mL) was
added 1 M aq HCl (2.0 mL) at 0 ꢁC. After being stirred at room
temperature for 3.5 h, the mixture was concentrated in vacuo. The
residue was dissolved in CH2Cl2 (80 mL), and then TsCl (6.6 g,
35 mmol), nBu2SnO (1.7 g, 6.8 mmol), and Et3N (4.8 mL, 34 mmol)
were added at 0 ꢁC. After being stirred at room temperature for
1.5 h, the reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers
were washed with 1 M aq HCl and brine, dried (Na2SO4), and then
evaporated. The residue was purified by silica gel column chro-
8% in 3 steps). 19: 1H NMR
d
0.90 (3H, t, J¼7.6 Hz), 0.91 (3H, t,
J¼7.6 Hz), 1.63 (2H, q, J¼7.6 Hz), 1.66 (2H, q, J¼7.6 Hz), 1.82 (2H,
complex), 2.26 (1H, br), 3.55 (1H, t, J¼8 Hz), 3.81 (2H, t, J¼6 Hz),
4.10 (1H, dd, J¼6, 8 Hz), 4.25 (1H, m); 13C NMR
d 8.1, 8.3, 29.7, 30.0,
35.5, 60.8, 70.1, 75.5, 113.0.
4.15. (2R)-1-[(4S)-2,2-Diethyl-[1,3]dioxolan-4-yl]-
pent-4-en-2-ol (20)
A mixture of NCS (154 mg, 1.2 mmol), K2CO3 (1.2 g, 8.7 mmol),
and MS 4 Å (0.9 g) in CH2Cl2 (4 mL) was stirred at 0 ꢁC for 5 min. To
this mixture was added a solution of 19 (155 mg, 0.89 mmol) in
CH2Cl2 (3 mL) at 0 ꢁC. After 5 min, a solution of PhSNHtBu (16 mg,
matography (hexane/EtOAc 3/2) to give 21 (6.38 g, 93% in 2 steps):
21
[a
]
ꢀ8.8 (c 0.5, CHCl3); IR (film) 3406, 2923, 1356, 1175 cmꢀ1
;
1H
D
NMR
d
1.34 (1H, ddd, J¼3.4, 9.3, 15 Hz), 1.58 (1H, ddd, J¼2.7, 8.6,
15 Hz), 2.09–2.23 (2H, complex), 2.35 (2H, br), 2.38 (3H, s), 3.85
(1H, m), 3.88 (1H, dd, J¼6.7, 10 Hz), 3.98 (1H, dd, J¼4.3, 10 Hz), 4.10
(1H, m), 5.03–5.09 (2H, complex), 5.70 (1H, m), 7.29 (2H, d,
88 m
mol) in CH2Cl2 (3 mL) was added at 0 ꢁC, and the mixture was
stirred at the same temperature for 3 h. The reaction was quenched
by the addition of H2O and filtered. The filtrate was extracted with
CHCl3, and the organic layers were washed with brine, dried
(Na2SO4), and then evaporated. The residue was purified by silica
gel column chromatography (hexane/EtOAc 5/1) to give an alde-
J¼8.3 Hz), 7.73 (2H, d, J¼8.3 Hz); 13C NMR
d 21.7, 38.1, 42.0, 66.6,
67.4, 73.6, 118.4, 127.8, 129.8, 132.3, 133.9, 144.9. HRMS (FAB) Calcd
for C14H20O5SNa [MþNa]þ: 323.0929. Found: m/z 323.0909.
hyde (120 mg): 1H NMR
d
0.90 (6H, t, J¼7.5 Hz), 1.63 (2H, q,
4.17. (4R,6R)-4,6-(Bis-triethylsiloxy)-oct-1-ene (22)
J¼7.5 Hz), 1.65 (2H, q, J¼7.5 Hz), 2.64 (1H, ddd, J¼1.3, 6.1, 17.2 Hz),
2.87 (1H, ddd, J¼1.6, 6.6,17.2 Hz), 3.53 (1H, t, J¼7.5 Hz), 4.21 (1H, dd,
To a solution of 21 (368 mg, 1.2 mmol) in DMF (8 mL) was added
imidazole (417 mg, 6.1 mmol) and TESCl (652 m
L, 3.7 mmol) at 0 ꢁC.
After being stirred at room temperature for 1.5 h, the reaction was
quenched by the addition of saturated aq NH4Cl, and the resulting
mixture was extracted with EtOAc. The organic layers were washed
with brine, dried (Na2SO4), and then evaporated. The residue was
J¼6.0, 8.2 Hz), 4.52 (1H, dt, J¼6.4,13.7 Hz), 9.82 (1H, t, J¼1.6 Hz); 13
C
NMR
d
8.1, 8.3, 29.7, 30.0, 35.5, 60.8, 70.1, 75.5, 113.0.
To a solution of allylmagnesium bromide (1.0 M solution in Et2O,
1.1 mL, 1.1 mmol) in Et2O (3 mL) was added a solution of the alde-
hyde (120 mg, 0.69 mmol) in Et2O (3 mL) at 0 ꢁC. After being stirred
at room temperature for 2 h, the reaction was quenched by the
addition of saturated aq NH4Cl, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was purified by
silica gel column chromatography (benzene/Et2O 20/1–10/1) to
purified bysilica gelcolumnchromatography(hexane/EtOAc 30/1)to
23
give tosylate (648 mg,100%): [
a
]
ꢀ10.1 (c 1.0, CHCl3); IR (film) 2955,
D
2877, 1367, 1189, 1178 cmꢀ1
;
1H NMR
d
0.55 (6H, q, J¼7.8 Hz), 0.56
(6H, q, J¼7.8 Hz), 0.90 (9H, t, J¼7.8 Hz), 0.93 (9H, t, J¼7.8 Hz),1.47 (1H,
ddd, J¼5.6, 8.1, 13.7 Hz), 1.58 (1H, ddd, J¼4.4, 5.9, 13.4 Hz), 2.14–2.26
(2H, complex), 2.44 (3H, s), 3.78–3.83 (2H, complex), 3.92–3.99 (2H,
complex), 5.00–5.04 (2H, complex), 5.72 (1H, m), 7.33 (2H, d, J¼8 Hz),
give 20 (55.5 mg, 29% in 2 steps) and 200 (63.5 mg, 33% in 2 steps).
21
20: [
a
]
D
ꢀ6.40 (c 1.61, CHCl3); IR (film) 3441, 2940, 1079, 919 cmꢀ1
;
1H NMR
d
0.897 (3H, t, J¼7.4 Hz), 0.902 (3H, t, J¼7.5 Hz), 1.61–1.73
7.78 (2H, d, J¼8. Hz); 13C NMR
d 5.1, 5.3, 6.9, 7.0, 21.7, 41.9, 42.6, 68.3,
(5H, complex), 1.78 (1H, ddd, J¼3.3, 7.3 14.3 Hz), 2.18–2.37 (3H,
complex), 3.53 (1H, t, J¼8.1 Hz), 3.90 (1H, m), 4.09 (1H, dd, J¼5.9,
7.9 Hz), 4.32 (1H, m), 5.11–5.16 (2H, complex), 5.82 (1H, m); 13C
69.2, 74.0,117.4,127.9,129.7,132.9,134.1,144.6. HRMS (FAB) Calcd for
C
26H49O5SSi2 [MþH]þ: 529.2839. Found: m/z 529.2865.
To a suspension of CuCN (329 mg, 3.7 mmol) in Et2O (2 mL) was
NMR
d
8.1, 8.3, 29.7, 30.0, 39.2, 42.3, 68.1, 70.1, 73.9, 112.6, 118.1,
added MeLi (0.92 M solution in Et2O, 8.0 mL, 7.4 mmol) at ꢀ78 ꢁC.
After being stirred at 0 ꢁC for 10 min, a solution of the tosylate
(648 mg,1.3 mmol) in Et2O (6 mL) was added at ꢀ78 ꢁC; the mixture
was stirred atroomtemperaturefor 15 h. Thereactionwas quenched
by the addition of 35% aq NH3, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried(Na2SO4), and evaporated. Theresiduewas purifiedbysilicagel
134.4. HRMS (FAB) Calcd for C12H23O3 [MþH]þ: 215.1647. Found: m/z
21
215.1664. 200: [
a
;
]
þ8.47 (c 1.29, CHCl3); IR (film) 3464, 2940,
D
1080, 919 cmꢀ1
1H NMR
d
0.83 (3H, t, J¼7.3 Hz), 0.84 (3H, t,
J¼7.6 Hz), 1.53–1.62 (5H, complex), 1.68 (1H, dt, J¼2.9, 14.2 Hz), 2.21
(2H, complex), 3.11 (1H, s), 3.45 (1H, t, J¼8.1 Hz), 3.83 (1H, m), 4.04
(1H, dd, J¼5.8, 7.8 Hz), 4.19 (1H, m), 4.99–5.07 (2H, complex), 5.77
(1H, m); 13C NMR
d
8.1, 8.3, 29.6, 30.0, 39.4, 41.9, 70.35, 70.42, 76.1,
column chromatography (hexane/EtOAc 50/1) to give 22 (370 mg,
113.4, 117.6, 134.5. HRMS (FAB) Calcd for C12H23O3 [MþH]þ:
215.1647. Found: m/z 215.1655.
81% in 2 steps): [
a]
ꢀ10.7 (c 1.0, CHCl3); IR (film) 2956, 2877, 1096,
22
D
1011 cmꢀ1; 1H NMR
d
0.597 (6H, q, J¼7.8 Hz), 0.603 (6H, q, J¼7.8 Hz),

9504
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
0.90 (3H, t, J¼7.3 Hz), 0.96 (18H, t, J¼7.8 Hz),1.39–1.51 (2H, complex),
residue was purified by silica gel column chromatography (hexane/
EtOAc 25/1) to give an aldehyde (562 mg): 1H NMR
0.60 (12H, q,
1.52–1.64 (2H, complex), 2.17–2.29 (2H, complex), 3.70 (1H, m), 3.81
d
(1H, m), 5.03–5.07 (2H, complex), 5.83 (1H, m); 13C NMR
d
5.3, 5.4,
J¼8 Hz), 0.88 (3H, t, J¼8 Hz), 0.96 (18H, t, J¼8 Hz), 1.42–1.76 (8H,
complex), 2.43(2H,t,J¼7.3 Hz),3.67(1H, m),3.76(1H, m),9.77(1H,s).
To a solution of the aldehyde (562 mg, 1.4 mmol) and 1,3-pro-
panedithiol (0.29 mL, 2.9 mmol) in CH2Cl2 (15 mL) was slowlyadded
BF3$OEt2 (0.29 mL, 2.3 mmol) at 0 ꢁC. After being stirred for 5.5 h,
the reaction was quenched by the addition of 1 M aq KOH, and the
resulting mixture was extracted with EtOAc. The organic layers were
washed with brine, dried (Na2SO4), and then evaporated. The resi-
7.0, 7.1, 9.5, 30.5, 42.6, 44.7, 69.8, 71.2, 116.8, 135.0. HRMS (ESI) Calcd
for C20H45O2Si2 [MþH]þ: 373.2958. Found: m/z 373.2942.
4.18. (5R,7R)-5,7-(Bis-triethylsiloxy)-non-2-enoic acid
methyl ester (23)
t
To a solution of 22 (157 mg, 0.42 mmol) in BuOH (2 mL)–H2O
(2 mL) was added OsO4 (39 mM solution in tBuOH, 0.54 mL,
due was purified by silica gel column chromatography (hexane/
23
21
m
mol) and NMO (99 mg, 0.84 mmol) at 0 ꢁC. After being stirred
EtOAc 1/1) to give 25 (355 mg, 93% in 2 steps): [
a]
ꢀ13.6 (c 1.0,
D
at room temperature for 21 h, the reaction was quenched by the
addition of saturated aq Na2SO3, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated. The residue was dissolved in
THF (4 mL)–H2O (1 mL), and 2,6-lutidine (0.073 mL, 0.72 mmol)
and NaIO4 (135 mg, 0.63 mmol) were added at 0 ꢁC. After being
stirred at room temperature for 4 h, the reaction was quenched by
the addition of saturated aq Na2SO3, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with brine,
dried (Na2SO4), and then evaporated.
CHCl3); IR (film) 3365, 2934, 2360,1090 cmꢀ1; 1H NMR
d 0.88 (3H, t,
J¼7.4 Hz), 1.38–1.63 (6H, complex), 1.68–1.85 (3H, complex), 2.05
(1H, m), 2.41 (2H, br), 2.71–2.87 (4H, complex), 3.79 (1H, m), 3.88
(1H, m), 3.99 (1H, t, J¼6.8 Hz); 13C NMR
d 10.2, 22.9, 26.0, 30.3, 30.5,
35.3, 36.9, 41.8, 47.4, 68.9, 70.7; Anal. Calcd for C12H24O4S2: C, 54.50;
H, 9.15; S, 24.25%. Found: C, 54.30; H, 9.08; S, 24.30%.
4.21. (4R,6R)-4-(3-[1,3]Dithian-2-yl-propyl)-6-ethyl-
2,2-dimethyl-[1,3]dioxane (18)
The residue was dissolved in PhMe (4 mL), and Ph3P]CHCO2Me
(281 mg, 0.84 mmol) was added at 0 ꢁC. After being stirred at room
temperature for 17 h, the reaction was quenched by the addition of
H2O, and the resulting mixture was extracted with EtOAc. The or-
ganic layers were washed with brine, dried (Na2SO4), and then
evaporated. The residue was purified by silica gel column chro-
A solution of 25 (5.9 mg, 22 mmol) in 2,2-dimethoxypropane
(1 mL) in the presence of Drierite and catalytic amounts of CSA was
stirred at 40 ꢁC for 2.5 h. The reaction was quenched by the addition
of NaHCO3, and filtered. The filtrate was concentrated in vacuo and
the residue was purified by PTLC (hexane/EtOAc 5/1) to give 18
21
(6.9 mg, 100%): [
a
]
D
ꢀ33.7 (c 1.0, CHCl3); IR (film) 2935, 1378,
matography (hexane/EtOAc 50/1) to give 23 (155 mg, 86% in 3
1225 cmꢀ1; 1H NMR
d
0.83 (3H, t, J¼7.3 Hz), 1.27 (3H, s), 1.28 (3H, s),
23
steps): [
a
]
ꢀ9.2 (c 1.0, CHCl3); IR (film) 2954, 2877, 1730, 1100,
1.34–1.57 (8H, complex), 1.70 (2H, q, J¼7.3 Hz), 1.79 (1H, m), 2.05
D
1009 cmꢀ1; 1H NMR
d
0.59 (6H, q, J¼8.0 Hz), 0.60 (6H, q, J¼8.0 Hz),
(1H, m), 2.72–2.85 (4H, complex), 3.61 (1H, m), 3.69 (1H, m), 3.98
0.87 (3H, t, J¼7.3 Hz), 0.95 (18H, t, J¼8.0 Hz), 1.42–1.49 (2H, com-
plex), 1.54–1.65 (2H, complex), 2.33 (1H, m), 2.42 (1H, m), 3.68 (1H,
m), 3.73 (3H, s), 3.90 (1H, m), 5.86 (1H, d, J¼15.6 Hz), 6.99 (1H, dt,
(1H, m); 13C NMR
d 9.8, 22.7, 24.8, 24.9, 26.1, 28.8, 30.51, 30.55, 35.4,
35.5, 38.5, 47.6, 66.4, 68.1, 100.1. Anal. Calcd for C15H28O2S2: C,
59.16; H, 9.27%. Found: C, 59.22; H, 9.25%.
J¼7.6, 15.6 Hz); 13C NMR
d 5.2, 5.4, 7.0, 7.1, 9.4, 30.5, 40.9, 44.8, 51.4,
69.1, 71.1, 122.9, 145.8, 166.6. Anal. Calcd for C22H46O4Si2: C, 61.34;
H, 10.76%. Found: C, 60.87; H, 10.91%.
4.22. (2S,3S,4S)-1-Benzyloxy-6-[1,3]dithian-9-([4R,6R]-
6-ethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-
(4-methoxybenzyloxy)-3-methylnonan-4-ol (26)
4.19. (5R,7R)-5,7-(Bis-triethylsiloxy)-nonan-1-ol (24)
To a solution of 16 (425 mg, 1.4 mol) in THF (5 mL) was added
nBuLi (1.63 M solution in hexane, 0.90 mL, 1.5 mmol) at 0 ꢁC. After
being stirred for 20 min, 5 (621 mg, 1.8 mmol) in THF (6 mL) was
added at 65 ꢁC, and the mixture was stirred for 5 h. The reaction
was quenched by the addition of saturated aq NH4Cl, and the
resulting mixture was extracted with EtOAc. The organic layers
were washed with brine, dried (Na2SO4), and then evaporated. The
residue was purified by silica gel column chromatography (hexane/
EtOAc 10/1–5/1) to give 26 (733 mg, 81%) as a diastereomeric
mixture, along with 18 (67 mg, 16%). 26: IR (film) 3484, 2935, 1514,
A mixture of 23 (73 mg, 0.17 mmol) in EtOAc (2 mL) in the pres-
ence of catalytic amounts of 10% Pd–C was stirred at room temper-
ature for 10 min under a hydrogen atmosphere. The mixture was
filtered and the filtrate was concentrated in vacuo to give a residue.
To a solution of the residue in CH2Cl2 (2 mL) was added DIBAL
(0.99 M solution in PhMe, 0.5 mL, 0.5 mmol) at 0 ꢁC. After being
stirred for 1 h, the reaction was quenched by the addition of satu-
rated aq NH4Cl, and the resulting mixture was extracted with EtOAc.
The organic layers werewashed with brine, dried (Na2SO4), and then
evaporated. The residue was purified by silica gel column chroma-
1248, 1037 cmꢀ1 1H NMR
; d 0.88–0.94 (5H, complex), 0.98 (1H, d,
tography (hexane/EtOAc 10/1) to give 24 (61 mg, 88% in 2 steps):
J¼7.3 Hz), 1.33 (3H, s), 1.34 (3H, s), 1.40–1.61 (9H, complex), 1.72–
1.82 (1H, complex), 1.86–2.05 (3.7H, complex), 2.08–2.17 (1H,
complex), 2.23 (0.3H, dd, J¼8.3, 15.1 Hz), 2.74–2.96 (4H, complex),
3.37 (0.3H, br), 3.50–3.55 (1.4H, complex), 3.61 (0.3H, dd, J¼4.4,
10.3 Hz), 3.65–3.71 (2H, complex), 3.72–3.80 (5H, complex), 4.07
(0.7H, m), 4.15 (0.3H, m), 4.51–4.58 (3H, complex), 4.65–4.71 (1H,
complex), 6.84–6.87 (2H, complex), 7.24–7.31 (3H, complex), 7.34–
7.37 (4H, complex). Anal. Calcd for C36H54O6S2: C, 66.47; H, 8.44%.
Found: C, 66.19; H, 8.41%.
22
[
a
]
ꢀ1.13 (c 1.0, CHCl3); IR (film) 3447, 2954, 2877,1459,1238,1061,
D
1009 cmꢀ1; 1H NMR
d
0.53 (12H, q, J¼7.8 Hz), 0.81 (3H, t, J¼7.8 Hz),
0.89 (18H, t, J¼7.8 Hz), 1.28–1.43 (6H, complex), 1.45–1.53 (2H,
complex), 3.57 (2H, t, J¼6.5 Hz), 3.59 (1H, m), 3.66 (1H, m); 13C NMR
d
5.3, 7.0, 9.5, 21.3, 30.5, 33.0, 37.6, 45.0, 62.9, 70.1, 71.3. Anal. Calcd for
21H48O3Si2: C, 62.31; H, 11.95%. Found: C, 62.05; H, 12.06%.
C
4.20. (3R,5R)-8-[1,3]Dithian-2-yl-octane-3,5-diol (25)
To a solution of 24 (586 mg, 1.5 mmol) in CH2Cl2 (15 mL) were
addedTEMPO(68 mg, 0.43 mmol)andbisacetoxyiodobenzene(BAIB,
700 mg, 2.2 mmol) at 0 ꢁC. After being stirred for 5.5 h, the reaction
was quenched by the addition of saturated aq Na2SO3, and the
resulting mixture was extracted with CHCl3. The organic layers were
washed with NaHCO3, dried (Na2SO4), and then evaporated. The
4.23. (2S,3R,4S)-4-Acetoxy-1-benzyloxy-6-[1,3]dithian-
9-[(4R,6R)-6-ethyl-2,2-dimethyl-[1,3]dioxolan-4-yl]-
3-methylnonan-2-ol (27)
A
mixture of 26 (27.3 mg, 42
mmol) and Ac2O (0.30 mL,
3.2 mmol) in pyridine (0.6 mL) in the presence of catalytic amounts

E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
9505
of DMAP was stirred at 0 ꢁC for 1.5 h. The reaction was quenched by
the addition of H2O, and the resulting mixture was extracted with
EtOAc. The organic layers were washed with 1 M aq HCl, saturated
aq NaHCO3, and brine, dried (Na2SO4), and then evaporated. The
residue was dissolved in CH2Cl2 (0.8 mL)–H2O (0.2 mL), to this so-
1.32–1.41 (2H, complex), 1.42–1.51 (4H, complex), 1.54–1.69 (4H,
complex), 1.78 (1H, dd, J¼5.1, 13 Hz), 1.94 (1H, qt, J¼4.2, 13 Hz), 2.02
(3H, s), 2.19 (1H, m), 2.88 (1H, br), 3.43 (1H, dd, J¼3.4, 9.8 Hz), 3.53
(1H, dd, J¼7.8, 9.8 Hz), 3.83 (1H, m), 3.99–4.04 (2H, complex), 4.57
(1H, d, J¼12.7 Hz), 4.62 (1H, d, J¼12.2 Hz), 5.21 (1H, dt, J¼5.0,
lution was added DDQ (19 mg, 85
m
mol) at 0 ꢁC. After being stirred
12.2 Hz), 7.28–7.35 (5H, complex); 13C NMR
d 5.3, 10.1, 19.3, 21.3,
at 0 ꢁC for 30 min, the mixture was filtered and the filtrate was
extracted with CHCl3. The organic layers were washed with satu-
rated aq NaHCO3, dried (Na2SO4), and then evaporated. The residue
30.4, 30.6, 33.3, 34.8, 35.8, 42.6, 66.4, 68.8, 70.1, 70.4, 71.2, 73.2, 97.6,
127.48, 127.52, 128.3, 138.0, 170.0. Anal. Calcd for C24H36O6: C,
68.54; H, 8.63%. Found: C, 68.18; H, 8.64%.
was purified by PTLC (hexane/EtOAc 2/1) to give 27 (14.7 mg, 61% in
22
2 steps) and 270 (7.4 mg, 32% in 2 steps). 27: [
a]
ꢀ14.3 (c 1.0,
4.26. (2S,3R,4S,6R,8R)-4-Acetoxy-2-benzyloxymethyl-
8-[(2R)-2-acetoxybutan-1-yl]-3-methyl-1,7-dioxa-
spiro[5.5]undecane (29)
D
CHCl3); IR (film) 3499, 2935, 1735, 1378, 1238 cmꢀ1; 1H NMR
d 0.83
(3H, t, J¼7 Hz), 0.87 (3H, d, J¼7 Hz), 1.26 (3H, s), 1.27 (3H, s), 1.35–
1.52 (8H, complex), 1.73–1.88 (5H, complex), 1.98 (3H, s), 2.17 (1H,
dd, J¼9, 16 Hz), 2.31 (1H, d, J¼16 Hz), 2.68–2.76 (5H, complex), 3.41
(2H, complex), 3.60 (1H, m), 3.70 (1H,m), 3.78 (1H, m), 4.44 (1H, d,
J¼12 Hz), 4.52 (1H, d, J¼12 Hz), 5.04 (1H, t, J¼7.6 Hz), 7.22–7.30 (5H,
A mixture of 28 (17.3 mg, 4.1 mmol) and Ac2O (0.3 mL) in pyridine
(0.6 mL) was stirred at room temperature for 1 h. The reaction was
quenched by the addition of H2O, and the resulting mixture was
extracted with EtOAc. The organic layers were washed with 1 M aq
complex); 13C NMR
d 8.7, 9.8, 20.2, 21.7, 24.8, 24.9, 25.1, 26.1, 26.3,
28.8, 36.1, 38.5, 39.0, 39.2, 39.4, 52.3, 66.5, 68.1, 69.3, 72.5, 73.4,
73.9, 100.1, 127.68, 127.72, 128.3, 137.8, 171.3. Anal. Calcd for
HCl and brine, dried (Na2SO4), and then evaporated. The residue was
21
purified by PTLC (hexane/EtOAc 3/1) to give 29 (19 mg, 100%): [a]
D
C
30H48O6S2: C, 63.34; H, 8.51; S, 11.27%. Found: C, 63.47; H, 8.65; S,
ꢀ75.7 (c 0.99, CHCl3); IR (film) 2940,1736,1242 cmꢀ1; 1H NMR
d 0.78
23
11.34%. 270: [
a
]
D
ꢀ11.0 (c 1.0, CHCl3); IR (film) 3482, 2935, 1734,
(3H, d, J¼6.8 Hz), 0.84 (3H, t, J¼7.3 Hz), 1.22 (1H, m), 1.38 (1H, dt,
J¼4.4, 13 Hz), 1.51–1.62 (8H, complex), 1.78 (1H, dd, J¼4.7, 13 Hz),
1.89 (1H, m),1.91 (3H, s), 2.00 (3H, s), 2.13 (1H, m), 3.43(1H, dd, J¼5.4,
10 Hz), 3.48 (1H, dd, J¼7.6, 10 Hz), 3.76 (1H, m), 3.94 (1H, br), 4.50
(1H, d, J¼12.2 Hz), 4.61 (1H, d, J¼12.2 Hz), 5.00 (1H, m), 5.24 (1H, dt,
J¼5.1, 12 Hz), 7.28–7.32 (5H, complex). HRMS (FAB) Calcd for
1377, 1237 cmꢀ1
;
1H NMR
d
0.90 (3H, t, J¼7.3 Hz), 0.98 (3H, d,
J¼7.3 Hz), 1.33 (3H, s), 1.35 (3H, s), 1.40–1.61 (8H, complex), 1.81–
1.96 (5H, complex), 2.02 (3H, s), 2.22 (1H, d, J¼14.2 Hz), 2.28 (1H, d,
J¼7.8 Hz), 2.32 (1H, d, J¼3.4 Hz), 2.76–2.79 (4H, complex), 3.48 (1H,
dd, J¼7.8, 9.3 Hz), 3.55 (1H, dd, J¼3.4, 9.3 Hz), 3.67 (1H, m), 3.77
(1H, m), 3.88 (1H, m), 4.55 (2H, s), 5.24 (1H, m), 7.30 (5H, complex);
C
26H38O7Na [MþNa]þ: 485.2515. Found: m/z 485.2544.
13C NMR
d 9.7, 9.9, 20.1, 21.6, 24.8, 24.9, 25.2, 26.2, 28.8, 36.1, 38.5,
38.7, 39.6, 40.3, 52.2, 66.4, 68.1, 70.2, 72.5, 73.2, 73.4, 100.1, 127.6,
127.7, 128.4, 137.8, 170.4. Anal. Calcd for C30H48O6S2: C, 63.34; H,
8.51; S, 11.27%. Found: C, 63.41; H, 8.63; S, 11.38%.
4.27. (2S,3R,4S,6R,8R)-4-Acetoxy-2-benzyloxymethyl-
8-[(2R)-2-(tert-butyldimethylsiloxy)-butan-1-yl]-
3-methyl-1,7-dioxa-spiro[5.5]undecane (30)
4.24. (2S,3R,4S,10R,12R)-4-Acetoxy-1-benzyloxy-6-
To a solution of 28 (13.7 mg, 0.033 mmol) in CH2Cl2 (1 mL) was
[1,3]dithian-3-methyl-tetradecane-2,10,12-triol (17)
added 2,6-lutidine (0.015 mL, 0.13 mmol) and TBSOTf (0.015 mL,
0.065 mmol) at ꢀ78 ꢁC. After being stirred at the same temperature
for 1 h, the reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers were
washed with brine, dried (Na2SO4), and then evaporated. The resi-
A mixture of 27 (20.4 mg, 36 mmol) in MeOH (1 mL)–H2O
(0.2 mL) in the presence of catalytic amounts of PPTS was stirred at
room temperature for 3 h. The reaction was quenched by the addi-
tion of H2O, and the resulting mixturewas extracted with EtOAc. The
organic layers were washed with brine, dried (Na2SO4), and then
due was purified by PTLC (hexane/EtOAc 5/1) to give 30 (15.5 mg,
22
89%): [
a
]
D
ꢀ47.9 (c 1.0, CHCl3); IR (film) 2936, 2857, 1744, 1244,
evaporated. The residue was purified by PTLC (hexane/EtOAc 1/2) to
1029 cmꢀ1; 1H NMR
d
0.03 (6H, s), 0.81 (3H, d, J¼6.8 Hz), 0.85 (3H, t,
22
give 17 (18.8 mg, 99%): [
a
]
ꢀ3.1 (c 1.0, CHCl3); IR (film) 3423, 2934,
J¼7.3 Hz), 0.87 (9H, s), 1.17 (1H, m), 1.37–1.44 (2H, complex), 1.49–
1.54(3H, complex),1.57–1.70(4H, complex),1.75 (1H, dd, J¼5,13 Hz),
1.87 (1H, qt, J¼4,13 Hz), 2.03 (3H, s), 2.22 (1H, m), 3.45 (1H, dd, J¼5.9,
9.8 Hz), 3.53 (1H, dd, J¼6.8, 9.8 Hz), 3.65–3.69 (2H, complex), 4.01
(1H, m), 4.50 (1H, d, J¼12.2 Hz), 4.59 (1H, d, J¼12.2 Hz), 5.27 (1H, dt,
D
1731, 1242, 1099 cmꢀ1; 1H NMR
d
0.93 (3H, t, J¼7.3 Hz), 0.94 (3H, d,
J¼7.3 Hz), 1.46–1.64 (8H, complex), 1.80–1.85 (2H, complex), 1.91–
1.95 (3H, complex), 2.05 (3H, s), 2.21–2.42 (2H, br), 2.24 (1H, dd,
J¼8.8, 15.7 Hz), 2.40 (1H, d, J¼15.7 Hz), 2.76–2.83 (5H, complex),
3.47–3.49 (2H, complex), 3.83–3.87 (2H, complex), 3.94 (1H, m), 4.51
(1H, d, J¼12.2 Hz), 4.58 (1H, d, J¼12.2 Hz), 5.10 (1H, dd, J¼6.6,
J¼5.0,12.2 Hz), 7.29–7.36 (5H, complex); 13C NMR
ꢀ4.34, ꢀ4.29, 5.1,
d
9.4, 18.1, 18.9, 21.3, 26.0, 30.3, 31.3, 33.0, 34.8, 36.0, 44.0, 67.6, 69.2,
70.2, 70.7, 71.5, 73.2, 97.4,127.3,127.4,128.2,138.4,170.0. Anal. Calcd
for C30H50O6Si: C, 67.37; H, 9.42%. Found: C, 67.28; H, 9.42%.
16.1 Hz), 7.29–7.37 (5H, complex); 13C NMR
d 8.6,10.2, 20.5, 21.7, 25.1,
26.2, 26.3, 30.3, 37.5, 38.8, 39.0, 39.4, 42.1, 52.2, 69.0, 69.3, 70.7, 72.8,
73.4, 73.9, 127.69, 127.73, 128.3, 137.8. Anal. Calcd for C27H44O6S2: C,
61.33; H, 8.39; S, 12.13%. Found: C, 61.13; H, 8.44; S, 12.15%.
4.28. (2S,3R,4S,6R,8R)-4-Acetoxy-8-[(2R)-2-(tert-butyl-
dimethylsiloxy)-butan-1-yl]-3-methyl-2-tosyloxymethyl-
1,7-dioxa-spiro[5.5]undecane (31)
4.25. (2S,3R,4S,6R,8R)-4-Acetoxy-2-benzyloxymethyl-8-
[(2R)-2-hydroxybutan-1-yl]-3-methyl-1,7-dioxa-
spiro[5.5]undecane (28)
A mixture of 30 (11.4 mg, 2.1 mmol) in MeOH (2 mL) in the
presence of catalytic amounts of 10% Pd–C was stirred at room
temperature for 10 min under a hydrogen atmosphere. The mixture
was filtered and the filtrate was concentrated in vacuo. The residue
A mixture of 17 (18.8 mg, 36 mmol) in TFE (25 mL) in the pres-
ence of LiBr (131 mg) was electrolyzed (anode: glassy carbon bea-
ker; cathode: Pt wire, current: 0.3 mA/cm2, 1.7 F/mol, C.C.E.). The
reaction mixture was extracted with EtOAc, and the organic layers
were washed with brine, dried (Na2SO4), and then evaporated. The
was dissolved in pyridine (2 mL), TsCl (41 mg, 21 mmol) and cata-
lytic amounts of DMAP were added. After being stirred at 50 ꢁC for
20 h, the reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers
were washed with saturated aq NH4Cl, dried (Na2SO4), and then
evaporated. The residue was purified by PTLC (hexane/EtOAc 3/1) to
residue was purified by PTLC (hexane/EtOAc 3/1) to give 28
21
(14.9 mg, 99%): [
a
]
ꢀ63.6 (c 1.0, CHCl3); IR (film) 3510, 2939, 1742,
D
1245 cmꢀ1; 1H NMR
d
0.79 (3H, d, J¼6.8 Hz), 0.95 (3H, t, J¼7.6 Hz),

9506
E. Honjo et al. / Tetrahedron 64 (2008) 9495–9506
23
give 31 (11.7 mg, 92% in 2 steps): [
a
]
ꢀ46.4 (c 1.0, CHCl3); IR (film)
References and notes
D
2936,1743,1368,1244,1178 cmꢀ1; 1H NMR
d 0.02 (3H, s), 0.04 (3H, s),
1. (a) Schmitz, H.; Jubinski, S. D.; Hooper, I. R.; Crook, K. E.; Price, K. E., Jr.; Lein, J.
J. Antibiot. 1965, 18, 82–88; (b) Kirst, H. A.; Mynderse, J. S.; Martin, J. W.; Baker,
P. J.; Paschal, J. W.; Steiner, J. L. R.; Lobkovsky, E.; Clardy, J. J. Antibiot. 1996, 49,
162–167; (c) Salomon, A. R.; Voehringer, D. W.; Herzenberg, L. A.; Khosla, C.
Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 14766–14771; (d) Salomon, A. R.;
Voehringer, D. W.; Herzenberg, L. A.; Khosla, C. Chem. Biol. 2001, 8, 71–80.
2. (a) Kihara, T.; Kusakabe, H.; Nakamura, G.; Sakurai, T.; Isono, K. J. Antibiot. 1981,
34, 1073–1074; (b) Sakurai, T.; Kihara, T. G.; Isono, K. Acta Crystallogr. 1983, C39,
295–297; (c) Kihara, T.; Isono, K. J. Antibiot. 1983, 36, 1236.
3. (a) Karwowski, J. P.; Jackson, M.; Maus, M. L.; Kohl, W. L.; Humphrey, P. E.; Tillis,
P. M. J. Antibiot. 1991, 44, 1312–1317; (b) Hochlowski, J. E.; Mullally, M. M.; Brill,
G. M.; Whittern, D. N.; Buko, A. M.; Hill, P.; McAlpine, J. B. J. Antibiot. 1991, 44,
1318–1330; (c) Burres, N. S.; Premachandran, U.; Frigo, A.; Swanson, S. J.;
Mollison, K. W.; Fey, T. A.; Krause, R. A.; Thomas, V. A.; Lane, B.; Miller, L. N.;
McAlpine, J. B. J. Antibiot. 1991, 44, 1331–1341.
0.75 (3H, d, J¼6.8 Hz), 0.87 (9H, s), 0.88 (3H, t, J¼6.8 Hz),1.15 (1H, m),
1.35–1.42 (2H, complex), 1.48–1.68 (7H, complex), 1.70–1.78 (2H,
complex), 2.01(3H, s), 2.16(1H, m), 2.45(3H, s), 3.57(1H, m), 3.65(1H,
m), 3.91 (1H, dd, J¼4.4, 9.3 Hz), 3.97 (1H, td, J¼2.0, 5.9 Hz), 4.08 (1H,
dd, J¼7.3, 9.3 Hz), 5.20 (1H, dt, J¼5.0, 12.2 Hz), 7.34 (2H, d, J¼8.3 Hz),
7.78 (2H, d, J¼8.3 Hz); 13C NMR
ꢀ4.3, 5.0, 9.4, 18.1, 18.56, 21.2, 21.7,
d
25.9, 30.1, 31.1, 32.7, 34.6, 35.7, 43.8, 67.7, 67.8, 69.6, 70.0, 71.3, 97.6,
127.8, 129.7, 132.9, 144.7, 169.9. Anal. Calcd for C30H50O8SSi: C, 60.17;
H, 8.42; S, 5.35%. Found: C, 60.11; H, 8.42; S, 5.63%.
4.29. (2S,3R,4S,6R,8R)-8-[(2R)-2-(tert-Butyldimethylsiloxy)-
butan-1-yl]-3-methyl-2-tosyloxymethyl-4-trimethylsiloxy-
1,7-dioxa-spiro[5.5]undecane (1)
4. Kirst, H. A.; Larsen, S. H.; Paschal, J. W.; Occolowitz, J. L.; Creemer, L. C.; Steiner,
J. L. R.; Lobkovsky, E.; Clardy, J. J. Antibiot. 1995, 48, 990–996.
5. (a) Smith, R. A.; Peterson, W. H.; McCoy, E. Antibiot. Chemother. 1954, 4, 962–
970; (b) Visser, J.; Weinauer, D. E.; Davis, R. C.; Peterson, W. H.; Nazarewicz, W.;
Ordway, H. J. Biochem. Microbiol. Technol. Eng. 1960, 2, 31–48; (c) Thompson,
R. Q.; Hoehn, M. M.; Higgens, C. E. Antimicrob. Agents Chemother. 1961, 474–479;
(d) Arnoux, B.; Garcia-Alvarez, M. C.; Marazano, C.; Das, B. C.; Pascard, C.;
Merienne, C.; Staron, T. J. Chem. Soc., Chem. Commun. 1978, 318–319; (e)
Wuthier, D.; Keller-Schierlein, W.; Wahl, B. Helv. Chim. Acta 1984, 67, 1208–
1216.
6. (a) Kutsumura, N.; Nishiyama, S. Tetrahedron Lett. 2005, 46, 5707–5709; (b)
Kutsumura, N.; Nishiyama, S. Bull. Chem. Soc. Jpn. 2006, 79, 468–478; (c) Kut-
sumura, N.; Nishiyama, S. J. Carbohydr. Chem. 2006, 25, 377–385.
7. Perron, F.; Albizati, K. F. Chem. Rev. 1989, 89, 1617–1661.
8. (a) Hungerbu¨hler, E.; Naef, R.; Wasmuth, D.; Seebach, D.; Loosli, H.-R.; Wehrli,
A mixture of 31 (12.8 mg, 0.021 mmol) and K2CO3 (9.0 mg,
0.065 mmol) in MeOH (1 mL) was stirred at 0 ꢁC for 3.5 h. The re-
action was quenched by the addition of H2O, and the resulting
mixture was extracted with EtOAc. The organic layers were washed
with brine, dried (Na2SO4), and then evaporated.
The residue was dissolved in DMF (1 mL), to this solution was
added TESCl (0.015 mL, 0.085 mmol), and imidazole (11 mg,
0.16 mmol) at 0 ꢁC. After being stirred at the same temperature for
1.5 h, the reaction was quenched by the addition of H2O, and the
resulting mixture was extracted with EtOAc. The organic layers
were washed with brine, dried (Na2SO4), and then evaporated. The
´
A. Helv. Chim. Acta 1980, 63, 1960–1970; (b) Yus, M.; Najera, C.; Foubelo, F.
Tetrahedron 2003, 59, 6147–6212.
9. Corey, E. J.; Bock, M. G. Tetrahedron Lett. 1975, 16, 2643–2646.
10. Takano, S.; Hatakeyama, S.; Ogasawara, K. J. Chem. Soc., Chem. Commun.
1977, 68.
residue was purified by PTLC (hexane/EtOAc 5/1) to give 1 (13 mg,
23
91% in 2 steps): [
a
]
ꢀ41.3 (c 1.0, CHCl3); IR (film) 2954, 2877, 1371,
11. Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553–3560.
12. Stork, G.; Zhao, K. Tetrahedron Lett. 1989, 30, 287–290.
13. (a) Porter, Q. N.; Utley, J. H. P. J. Chem. Soc., Chem. Commun. 1978, 255–256; (b)
Platen, M.; Steckhan, E. Tetrahedron Lett. 1980, 21, 511–514; (c) Cristau, H. J.;
Chabaud, B.; Niangoran, C. J. Org. Chem. 1983, 48, 1527–1529; (d) Lebouc, A.;
Simonet, J.; Gelas, J.; Dehbi, A. Synthesis 1987, 320–321; (e) Martre, A.-M.;
Mousset, G.; Rhlid, R. B.; Veschambre, H. Tetrahedron Lett. 1990, 31, 2599–
2602.
14. (a) Mori, K.; Sku, Y.-B. Tetrahedron 1988, 44, 1035–1038; (b) Sasaki, M.; Tanino,
K.; Miyashita, M. Org. Lett. 2001, 3, 1765–1767.
15. Dounay, A. B.; Urbanek, R. A.; Frydrychowski, V. A.; Forsyth, C. J. J. Org. Chem.
2001, 66, 925–938.
1179, 1076 cmꢀ1
;
1DH NMR
d 0.04 (3H, s), 0.05 (3H, s), 0.55 (3H, t,
J¼8 Hz), 0.57 (3H, t, J¼8 Hz), 0.72 (3H, d, J¼6.8 Hz), 0.877 (9H, s),
0.884 (3H, t, J¼7.3 Hz), 0.93 (9H, t, J¼8 Hz), 1.18 (1H, m), 1.25–1.70
(10H, complex), 1.73–1.79 (2H, complex), 2.45 (3H, s), 3.57 (1H, m),
3.65 (1H, m), 3.88 (1H, m), 3.94 (1H, dd, J¼4.9, 9.8 Hz), 4.06 (1H, dd,
J¼7.8, 9.8 Hz), 4.10–4.15 (2H, complex), 7.34 (2H, d, J¼8.2 Hz), 7.80
(2H, d, J¼8.2 Hz); 13C NMR
d
ꢀ4.4, ꢀ4.3, 4.3, 4.9, 6.9, 9.6, 18.2, 18.6,
21.7, 26.0, 30.5, 31.4, 34.6, 36.4, 39.7, 44.2, 66.7, 67.7, 68.4, 70.7, 71.9,
97.7, 127.8, 129.7, 133.0, 144.6. Anal. Calcd for C34H62O7SSi2: C,
60.85; H, 9.31; S, 4.78%. Found: C, 61.18; H, 9.47; S, 5.08%.
16. Shiina, I.; Shibata, J.; Ibuka, R.; Imai, Y.; Mukaiyama, T. Bull. Chem. Soc. Jpn. 2001,
74, 113–122.
17. Martinelli, M. J.; Vaidyanathan, R.; Pawlak, J. M.; Nayyar, N. K.; Dhokte, U. P.;
ˇ
Doecke, C. W.; Zollars, L. M. H.; Moher, E. D.; Khau, V. V.; Kosmrlj, B. J. Am. Chem.
Soc. 2002, 124, 3578–3585.
Acknowledgements
18. (a) Amano, Y.; Inoue, K.; Nishiyama, S. Synlett 2008, 134–136; (b) Amano, Y.;
Nishiyama, S. Tetrahedron Lett. 2006, 47, 6505–6507.
19. Smith, A. B.; Chen, S. S.-Y.; Nelson, F. C.; Reichert, J. M.; Salvatore, B. A. J. Am.
Chem. Soc. 1995, 117, 12013–12014.
Thiswork wassupported byHigh-TechResearchCenterProjectfor
Private Universities: matching fund subsidy from MEXT, 2006–2011.