Efficient synthesis of the deoxysugar part of versipelostatin by direct and stereoselective glycosylation and revision of the structure of the trisaccharide unit

Article abstract of DOI:10.1002/asia.200800448

Efficient synthesis of the deoxysugar part of versipelostatin (VST) was achieved by direct and stereoselective glycosylation of the reduced VST aglycon. Activation of 2-deoxyglycosyl imidate with IBr under basic conditions enables α-selective glycosylatio

Full text of DOI:10.1002/asia.200800448

FULL PAPERS
DOI: 10.1002/asia.200800448
Efficient Synthesis of the Deoxysugar Part of Versipelostatin by Direct and
Stereoselective Glycosylation and Revision of the Structure of the
Trisaccharide Unit
Hiroshi Tanaka,*[a] Atsushi Yoshizawa,[a] Shuhei Chijiwa,[b] Jun-ya Ueda,[b]
Motoki Takagi,[b] Kazuo Shin-ya,[c] and Takashi Takahashi*[a]
Abstract: Efficient synthesis of the de-
oxysugar part of versipelostatin (VST)
was achieved by direct and stereoselec-
tive glycosylation of the reduced VST
aglycon. Activation of 2-deoxyglycosyl
imidate with IBr under basic conditions
enables a-selective glycosylation of b-
2-deoxylglycosides without anomeriza-
tion. Comparison of the synthetic and
natural VST products using NMR indi-
cates that versipelostatin has a b-d-dig-
itoxose-(1,4)-a-l-oleandrose-(1,4)-b-d-
digitoxose trisaccharide. In addition,
results of a biological assay indicate
that the deoxyoligosaccharide unit of
the synthetic glycoside was important
for biological activity of the compound.
Keywords: glycosides
· glycosyla-
tion · iodine · oxidative activation ·
synthetic methods
Introduction
dates and biochemical probes. However, the synthesis of oli-
godeoxysaccharides using a simple protocol remains difficult
owing to the lack of hydroxyl groups.[3] For instance, as a
result of the anomeric effect, 2-deoxy-b-glycosides are not
thermodynamically or kinetically favored reaction products.
To overcome these problems, several methods for the direct
b-selective glycosylation are available, in which a-glycosyl
halides and glycosyl phosphates are used as glycosyl
donors.[4] Recently, we reported an effective method for
direct b-selective glycosylation with 2-deoxyglycosides based
on activation of 2-deoxyglycosyl imidates with I2.[5] In con-
trast to the b-glycosides, 2-deoxy-a-glycosides are more
readily synthesized.[6] The a-glycosides are thermodynami-
cally favored products and can be prepared by glycosidation
under relatively strong acidic conditions. However, these
thermodynamically controlled a-glycosylation methods
cannot be adapted to the glycosylation of 2-deoxy-b-glyco-
sides as a result of anomerization and/or cleavage of the
pre-installed b-glycosides. Therefore, an effective method
for the synthesis of complex 2-deoxyoligosaccharides with
both a- and b-glycosidic linkages is still needed.
Deoxysugars are frequently found in naturally occurring,
biologically active compounds that contain macrocyclic and
aromatic aglycons.[1] Glycosylation of aglycons with 2-deoxy-
sugars is an important strategy for tuning the physical prop-
erties of naturally occurring compounds.[2] In addition, deoxy-
sugars also act as effective pharmacophores for binding re-
ceptor proteins or DNA. Therefore, modification of the de-
oxysugars of these natural products is an effective and at-
tractive strategy for the development of new drug candi-
[a] Prof. Dr. H. Tanaka, A. Yoshizawa, Prof. Dr. T. Takahashi
Department of Applied Chemistry
Graduate School of Science and Engineering
Tokyo Institute of Technology
2-12-1-S1-35 Ookayama, Meguro, Tokyo 152-8552 (Japan)
Fax : (+81)3-5734-2471
E-mail: thiroshi@apc.titech.ac.jp
ttak@apc.titech.ac.jp
[b] Dr. S. Chijiwa, Dr. J.-y. Ueda, Dr. M. Takagi
Biomedical Information Research Center (BIRC)
Japan Biological Informatics Consortium (JBIC)
2-42 Aomi, Koto-ku, Tokyo 135-0064 (Japan)
Versipelostatin (VST 1) was the first compound discov-
ered to specifically inhibit expression of GRP78 elicited by
glucose starved conditions such as the treatment of 2-deoxy-
glucose. VST 1 causes robust cell death during cellular
stress, but exhibits only weak cytotoxicity under normal con-
ditions.[7,8] VST 1 consists of a macrocyclic aglycon that
bears a deoxytrisaccharide unit (b-d-digitoxose-(1,4)-a-d-
[c] Dr. K. Shin-ya
Biological Systems Control Team
Biomedicinal Information Research Center
National Institute of Advanced Industrial Science and Technology
2-42 Aomi, Koto-ku, Tokyo 135-0064 (Japan)
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Chem. Asian J. 2009, 4, 1114 – 1125

oleandrose-(1,4)-b-d-digitoxose). Our interest in both the
biology and structure of the deoxytrisaccharide unit motivat-
ed us to develop an effective method for the synthesis of the
deoxysugar of VST[9] and to evaluate its biological activity.
Herein, we describe an efficient synthesis of the VST trisac-
charides attached to the reduced VST aglycon by a direct
and stereoselective glycosidation of 2-deoxyglycosides. We
also report the effects of the deoxysugar of VST on the bio-
logical activity and the structure of the sugar portion of
VST.
ditions. Two approaches for the synthesis of the deoxytrisac-
charide 2 were examined. One is based on a stepwise syn-
thetic strategy (I!II!III) and the other, on a convergent
synthetic strategy involving coupling of deoxytrisaccharide
unit 6 and aglycon 3 (IV). The d-digitoxosyl imidate 4 un-
derwent direct b-selective glycosidation by activation of the
glycosyl imidates using our previously reported method. In-
corporation of the a-oleandroside requires efficient a-selec-
tive glycosylation to produce the 2-deoxy-b-glycoside bear-
ing a-glycoside without anomerization.
Table 1 shows a-selective glycosidation of a 2-deoxysugar
under basic conditions initiated by activation of glycosyl imi-
dates 7a–c with IBr.[10] Treatment of glycosyl imidate 7a and
Results and Discussion
Scheme 1 shows our strategy for the synthesis of the VST
trisaccharide 2 attached to a reduced VST aglycon by direct
and stereoselective glycosidation of the d-digitoxoside 4 and
the d-oleandroside 5. Reduction of the b-hydroxyl ketone at
the 7 position to a hydroxyl group might improve the chemi-
cal stability of the aglycon under both acidic and basic con-
Table 1. a-Selective glycosidation of the 2,6-dideoxyglycosyl imidates 7
initiated by activation with IBr.
entry
Donor
R2
Time [h]
Product
Yield [%]
a/b[a]
1
7a
7a
7a
7b
7c
BnSO2
BnSO2
BnSO2
Ac
20
80
0.1
15
10
9a
9a
9a
9b
9c
87
87
91
82
77
93:7
92:8
33:67
89:11
77:23
2[b]
3[c]
4
5
Bn
[a] Ratio estimated from 1H NMR spectral data. [b] The reaction was
conducted without addition of DIEA. [c] Treatment with only IBr.
acceptor 8 with IBr in the presence of Bu4NBr at 08C, fol-
lowed by addition of N,N-diisopropylethylamine (DIEA)
provided a-glycoside 9a as a major product in 87% yield
with a/b=97:3. Bu4NBr played an important role in the a-
selective glycosidation.[11] Addition of DIEA shortened the
reaction time without adverse effects on yield or a-selectivi-
ty. The effects of various protecting groups were examined
(Table 1, entries 4 and 5). Glycosidation of the 4-O-acetyl
and benzyl derivatives 7b and 7c provided a-glycoside 9b
and 9c in good yields but with reduced a-selectivity. These
results indicate that a strong electron-withdrawing protect-
ing group at the C4 position results in excellent a-selective
glycosidation.
Scheme 1. Strategy for the synthesis of the VST trisaccharide 2 attached
on a reduced VST aglycon.
To demonstrate the feasibility of the a-selective glycosida-
tion, we next applied the method to glycosylation of glycosyl
acceptors 10a–d (Table 2). Treatment of the 2-deoxysugar
10b possessing a hydroxyl group at the C3 position with gly-
cosyl imidate 7a under the above described conditions pro-
vided the corresponding a-glycoside 11b in good yield and
selectivity. Glycosylation of the 2-deoxy-b-glycoside 10c
with the imidate 7a provided trisaccharide 11c without
anomerization of the preinstalled b-glycoside. The steroid
derivative 10d also acted as an effective glycosyl acceptor
for the a-selective glycosidation. However, glycosylation of
Abstract in Japanese:
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H. Tanaka, T. Takahashi et al.
FULL PAPERS
Table 2. a-Selective glycosidation of the 2,6-dideoxyglycosyl imidate 7a
initiated by activation with IBr.
pyridine (DMAP) resulted in acetylation of all hydroxyl
groups, except for tetronic acid, to provide the hexaacetylat-
ed VST derivative 12 in 90% yield. Treatment of the re-
maining tetronic acid unit with pivaloyl chloride and
TMEDA at reflux in CH2Cl2, followed by hydrolysis of the
deoxytrisaccharide unit under mildly acidic conditions pro-
vided the reduced aglycon 3 in 85% yield in 2 steps. The ste-
reochemistry at the C7 position was determined to be S
1
based on H NMR analysis, which showed a broad singlet
for the C7 position.
The glycosylation of the reduced VST aglycon 3 with de-
oxysugars is shown in Scheme 2. Treatment of the reduced
VST aglycon 3 and 2.5 equivalents of the d-digitoxosyl imi-
[5,12]
date 4 with I2
in the presence of a catalytic amount of
triethyl silane[13] provided the b-digitoxoside 15 in 82%
yield with excellent b-selectivity (a/b=5:95). Protection of
the tetronic acid was required during glycosylation because
use of the free tetronic acid 14 as a glycosyl acceptor results
in glycosylation of the tetronic acid. Selective deprotection
of the Lev group of 15 with NH2NH2·H2O afforded acceptor
16 in 90%. The a-selective glycosylation of acceptor 16 with
the d-oleandrosyl imidate 5 was conducted. p-Nitrophenyle-
thylsulfonyl (Npes) ester[14] was used as a strong electron-
withdrawing protecting group at the C4 position instead of
benzylsulfonyl ester[15] because it can be selectively removed
under mildly basic conditions in the presence of ester pro-
tecting groups. Treatment of both acceptor 16 and 2.5 equiv-
alents of d-oleandrosyl imidate 5 with IBr in the presence of
Bu4NBr at 08C, followed by addition of DIEA to the reac-
tion mixture at the same temperature, provided the a-d-ole-
androside 17 in 75% yield with excellent a-selectivity (a/b=
95:5). Selective removal of the Npes protecting group was
entry
Acceptor
Product
Yield [%]
a/b[a]
1
2
3
4
10a
10b
10c
10d
11a
11b
11c
11d
91
87
86
83
80:20
91:9
92:8
90:10
1
[a] Ratio estimated from H NMR spectral data.
the primary alcohol 10a resulted in good coupling yield, but
moderate a-selectivity.
Synthesis of the reduced VST derivative 2 was then exam-
ined. Scheme 2 shows the preparation of the partially-pro-
tected reduced VST aglycon 3 from VST 1. Chemo- and
stereo-selective reduction of a ketone in VST 1 with l-selec-
tride afforded the reduced VST 2 in 89%. Treatment of the
reduced VST 2 with Ac2O and N,N,N’,N’-tetramethylethyle-
nediamine (TMEDA) in the presence of 4-dimethylamino-
achieved by 1,8-diazabicycloACHTNUTRGNE[UNG 5.4.0]undec-7-ene (DBU) treat-
ment to afford acceptor 18 in 77% yield. Pivaloate was an
effective protecting group for tetronic acid because it sur-
vived under the conditions used for removal of the Npes
group. Finally, b-selective glycosylation of acceptor 18 with
d-digitoxosyl imidate 4 was achieved by using I2 and triiso-
propylsilane to provide the protected, reduced VST deriva-
tive 20 in 80% yield with good b-selectivity (a/b=4:96).
Use of triethylsilane instead of triisopropylsilane resulted in
formation of a significant amount of the triethylsilyl ether
19. Treatment of the protected VST derivative 20 with
NaOMe at reflux for 24 h provided the reduced VST deriva-
tive 21 in good yield. Hydrolysis of the tetronic acid moiety
was not observed under these reaction conditions. However,
1H NMR data of the synthetic reduced VST derivative 21
was identical with that of the reduced natural product 2.
We next examined the synthesis of the trisaccharide deriv-
ative 26, which has an a-l-oleandroside instead of an a-d-
oleandroside (Scheme 3). The a-selective glycosidation of
the l-oleandrosyl imidate 22 was achieved, using the proce-
dure described for glycosidation of the d-oleandrosyl imi-
date 5, to afford the a-l-oleandroside 23 in comparable
yield and a-selectivity (80%, a/b=95:5). Selective removal
of the Npes protecting group (75%), followed by b-selective
glycosidation of the d-digitoxosyl imidate 4 provided the
Scheme 2. Reagents and conditions: a) l-selectride, THF, 788C to RT,
89%. b) Ac2O, TMEDA, DMAP, CH2Cl2, RT, 90%. c) PivCl, TMEDA,
DMAP, CH2Cl2, reflux. d) 20% TFA in CH2Cl2:MeOH (9:1), 85% from
12.
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Chem. Asian J. 2009, 4, 1114 – 1125

Efficient Synthesis of Deoxysugar Part of Versipelostatin
Scheme 3. Reagents and conditions: a) 4, I2, Et3SiH, MS-4ꢁ, toluene, ꢀ948C, 82%, a/b=95:5; b) H2NNH2·H2O, Py, AcOH, 90%; c) 5, IBr, TBAB, MS-
4ꢁ, CH2Cl2, 08C then DIEA, 75%, a/b=95:5; d) DBU, CH3CN, 77% for 18, 75% for 24; e) 5, I2, iPr3SiH, MS-4ꢁ, toluene, ꢀ948C, 80%, a/b=4:96 for
20, 81%, a/b=4:96 for 25; f) NaOMe, MeOH, reflux, 24 h, 75% for 21, 75% for 26; g) 22, IBr, TBAB, MS-4ꢁ, CH2Cl2, 08C then DIEA, 80%, a/b=
95:5.
protected trisaccharide 25 in 81% yield with good b-selec-
tivity (a/b=6:94). Removal of the all acyl protecting groups
under basic conditions afforded the trisaccharide derivative
naturally occurring VST trisaccharide has an l-oleandroside
instead of a d-oleandroside.[16]
Convergent synthesis of the reduced VST derivative 25
from trisaccharide donor 6 and aglycon 3 was conducted
(Scheme 4). The trisaccharide glycosyl donor 6 was prepared
from the silyl b-glycoside 27. Treatment of the d-b-digitoxo-
1
26 in 75% yield. H and 13C NMR data of the synthetic re-
duced VST derivative 26 were consistent with those of the
reduced natural product 2. These results indicate that the
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H. Tanaka, T. Takahashi et al.
FULL PAPERS
Table 3. Cytotoxicity of the VST derivatives 1, 2, 21, 26, and 32–35
against HeLa cells under glucose-deprived conditions.
Entry
compound
IC50 [mM]
1
2
3
4
5
6
7
8
VST (1)
2[a]
21
26
32
33
34
35
1.27
2.72
10.8
2.69
6.74
12.8
>20
>20
[a] Prepared from natural product.
by hydrolysis of 24, 18, 15, and 3, respectively.[17] Reduction
of the ketone at the C7 position did not affect the cytotoxic-
ity (Table 3, entry 2). The activity of the reduced synthetic
VST 21, which reportedly has a trisaccharide derivative, was
significantly less than that of the reduced natural product
VST 2. On the other hand, the trisaccharide derivative 26,
which has an l-oleandoroside, exhibited cytotoxicity compa-
rable to that of 2. These results also support the conclusion
that the natural VST trisaccharide was b-d-digitoxose-(1,4)-
a-l-oleandrose-(1,4)-b-d-digitoxose. In addition, the differ-
ence of biological activities between disaccharides 32 and 33
clearly indicates that l-oleandoroside is important for exhib-
iting the biological activity. On the other hand, cytotoxicity
induced by monosaccharide 34 and aglycon 35 was not ob-
served. These results clearly indicate that the naturally oc-
curring VST has a trisaccharide with l-oleandoroside. In ad-
dition, the disaccharide unit ((1,4)-a-l-oleandrose-(1,4)-b-d-
digitoxose)) was important for the biological activity of
VST.
Scheme 4. Reagents and conditions; a) 5, IBr, TBAB, MS-4ꢁ, CH2Cl2,
08C then DIEA, 96%, a/b=94:6; b) DBU, CH3CN, 77%; c) 4, I2,
Et3SiH, MS-4ꢁ, toluene, ꢀ948C, 85%, a/b=5:95; d) HF·pyridine, pyri-
dine, RT, 80%; e) CCl3CN, CsCO3, CH2Cl2, RT, 89%; f) 3, I2, Et3SiH,
MS-4ꢁ, toluene, ꢀ948C, 40%, a/b=5:95.
side 27 and 1.5 equivalents of the the l-oleandrosyl imidate
4 with IBr in the presence of tetrabutylammoniumbromide
(TBAB), followed by addition of DIEA afforded the a-l-
oleandroside 28 in 96% yield with excellent a-selectivity (a/
b=96:4). Selective removal of the Npes protecting group
was achieved by DBU treatment to afford acceptor 29 in
77% yield. The b-selective glycosylation of acceptor 29 with
d-digitoxosyl imidate 4 was achieved by using I2 and triiso-
propylsilane to provide the VST trisacchride 30 in 86%
yield with good b-selectivity (a/b=5:95). Cleavage of the
silyl ether by HF·pyridine in pyridine, followed by reaction
of the resulting hemiacetal with CCl3CN provided the glyco-
syl imidate 6 in 89% yield as an anomeric mixture. Coupling
of the trisaccharide donor 6 and the reduced VST aglycon 3
was examined. Treatment of the reduced VST aglycon 3 and
2.0 equivalents of the trisaccharide donor 6 with I2 in the
presence of a catalytic amount of triethylsilane[13] provided
the reduced VST derivative 26 in 40% yield with excellent
b-selectivity (a/b=5:95). Although the coupling yield of the
method is moderate, this approach would be effective for
the synthesis of sugar derivatives from aglycon whose availa-
bility is limited.
Conclusions
In conclusion, we report an efficient synthesis of reduced
VST derivatives from the reduced VST aglycon 3 by direct
and stereoselective glycosidation. Activation of the 2-deoxy-
glycosyl imidates with IBr in the presence of a halide ion,
followed by exposure to basic conditions enabled a-selective
glycosidation of 2-deoxysugars without anomerization of the
pre-installed 2-deoxy-b-glycosides. 1H NMR analysis and
biological assay of the synthetic derivatives confirmed that
the VST trisaccharide contained l-oleandrose. In addition,
the deoxytrisaccharide unit strongly influenced the biologi-
cal activity of VST. The synthesis of various sugar-modified
VST derivatives using this method is currently in progress.
We next examined the cytotoxicity of the VST derivatives
1, 2, 21, 26, and 32–35 in HeLa cells under glucose-depriva-
tion (Table 3).[8] The VST derivatives 32–35 were prepared
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Chem. Asian J. 2009, 4, 1114 – 1125

Efficient Synthesis of Deoxysugar Part of Versipelostatin
1H, J=9.2 Hz, J=9.2 Hz), 4.23 (d, 1H, J=14.0 Hz), 3.87 (ddd, 1H, J=
5.3 Hz, J=8.7 Hz, J=11.1 Hz), 3.64–3.74 (m, 2H), 3.36 (dq, 1H, J=
6.3 Hz, J=9.2 Hz), 3.27–3.32 (m, 4H), 2.44 (ddd, 1H, J=1.9 Hz, J=
4.8 Hz, J=12.6 Hz), 2.25 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 1.62–1.72 (m,
2H), 1.29 (d, 3H, J=6.3 Hz), 1.27 ppm (d, 3H, J=6.3 Hz); 13C NMR
(100 MHz, CDCl3): d=138.9, 137.2, 130.6, 128.8, 128.7, 128.6, 128.3,
127.6, 127.5, 99.7, 98.2, 84.1, 83.3, 76.1, 75.5, 72.0, 70.6, 70.3, 66.6, 57.5,
54.6, 36.9, 35.7, 18.3, 17.9 ppm; IR (solid): n˜ =3032, 2935, 1496, 1455,
Experimental Section
General Techniques
NMR spectra were recorded on a JEOL Model EX-270 (270 MHz for
1H, 67.8 MHz for 13C) or a JEOL Model ECP-400 (400 MHz for 1H,
100 MHz for 13C) in the indicated solvent. Chemical shifts were reported
in part per million (ppm) relative to the signal (0.00 ppm) for internal tet-
1
1355, 1051, 986, 834, 737, 697 cmꢀ1
; HRMS (ESI-TOF) calcd for
ramethylsilane solutions in CDCl3. H NMR spectral data are reported as
C34H42O9S [M+Na]+ m/z=649.2447, found: 649.2420.
follows: CDCl3 (7.26 ppm) or CD2Cl2 (5.30 ppm). 13C NMR spectral data
are reported as follows: CDCl3 (77.1 ppm). NMR multiplicities are re-
ported using the following abbreviations. (s: singlet, d: doublet, t: triplet,
q: quartet m: multiplet, br: broad, J: coupling constants in Hertz.). Infra-
red spectra (IR) were recorded on a Perkin–Elmer Spectrum 1. Only the
strongest and/or structurally important absorbances are reported as the
IR data given in cmꢀ1. Optical rotations were measured on a JASCO
model P-1020 polarimeter. The reactions were monitored by thin layer
chromatography carried out on Merck precoated TLC plates (60F-254)
using UV light and p-anisaldehyde H2SO4 ethanol solution. Flash column
chromatography separations were performed using silica gel (KANTO,
silica gel 60 N, spherical, neutral, 40–100 mm). NH column chromatogra-
phy separations were performed using silica gel (FUJI SILYSIA, NH-
functionalized silica gel, 100–200 mesh). Gel permeation chromatography
(GPC) for qualitative analysis was performed on Japan Analytical Indus-
try Model LC908 (recycling preparative HPLC) using a polystylene gel
11a: According to the method for the synthesis of 9a, a mixture of 10a
(22.1 mg, 47.7 mmol), 7a (38.3 mg, 71.5 mmol), and MS-4ꢁ (71.5 mg) in
CH2Cl2 (0.953 mL) was treated with a mixture of 1.00m IBr in CH2Cl2
(95.3 mL, 95.3 mmol) and TBAB (38.4 mg, 119 mmol) at 08C for 2 h. N,N-
Diisopropylethylamine (4.18 mL, 24.0 mmol) was then added to the reac-
tion mixture. After being stirred for 10 h at the same temperature, to
give 11a (36.1 mg, 43.0 mmol, 91%, b/a=20:80) after purification. The
a,b isomers were separated by chromatography on silica gel with hexane/
ethyl acetate 85:15. a-11a: ½aꢁ2D0 =+47.78 (c=0.685, CHCl3); 1H NMR
(400 MHz, CDCl3): d=7.20–7.40 (m, 25H), 5.02 (d, 1H, J=10.6 Hz),
4.96 (d, 1H, J=11.1 Hz), 4.92 (d, 1H, J=3.4 Hz), 4.82 (d, 1H, J=
10.6 Hz), 4.81 (d, 1H, J=12.6 Hz), 4.70 (d, 1H, J=12.6 Hz), 4.66 (d, 1H,
J=11.1 Hz), 4.62 (d, 1H, J=3.4 Hz), 4.54 (d, 1H, J=11.1 Hz), 4.47 (d,
1H, J=11.1 Hz), 4.36 (d, 1H, J=13.5 Hz), 4.35 (dd, 1H, J=9.2 Hz, J=
9.2 Hz), 4.21 (d, 1H, J=13.5 Hz), 4.02 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
3.98 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=11.1 Hz), 3.71–3.80 (m, 3H),
3.47–3.59 (m, 3H), 3.37 (s, 3H), 2.42 (dd, 1H, J=4.8 Hz, J=12.6 Hz),
1.68 (ddd, 1H, J=3.4 Hz, J=11.1 Hz, J=12.6 Hz), 1.18 ppm (d, 3H, J=
6.3 Hz); 13C NMR (100 MHz, CDCl3): d=138.7, 138.2, 137.5, 130.7, 128.8,
128.8, 128.6, 128.6, 128.2, 128.1, 128.1, 128.0, 127.8, 127.6, 98.0, 97.1, 84.6,
82.3, 80.1, 77.9, 75.9, 75.0, 74.0, 73.4, 70.7, 69.8, 66.1, 66.0, 57.4, 55.2, 35.3,
column (JAIGEL-1H, 20 mm
ꢂ 600 mm). Detection of products was
made using a UV detector (Japan Analytical Industry Model 310) and a
refractive index detector (Japan Analytical Industry Model RI-5). ESI-
TOF mass spectra were measured with P. E. Biosystems TK-3500 Bio-
spectrometry Workstation. Dry THF, dry toluene, and dry ether were dis-
tilled from sodium wire containing a catalytic amount of benzophenone.
Dry CH2Cl2 was distilled from P2O5. Dry DMF and dry triethylamine
were distilled from CaH2. Dry methanol and dry ethanol were distilled
from magnesium contained with a catalytic amount of iodine.
17.7 ppm; IR (neat): n˜ =2924, 1455, 1357, 1160, 1093, 1073, 993 cmꢀ1
;
HRMS (ESI-TOF) calcd for C48H54O11S [M+Na]+ m/z=861.3285, found:
861.3286; b-11a: ½aꢁ2D5 =+12.78 (c=1.02, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7.20–7.52 (m, 25H), 5.00 (d, 1H, J=11.1 Hz), 4.90 (d, 1H,
J=11.6 Hz), 4.81 (d, 1H, J=11.1 Hz), 4.79 (d, 1H, J=12.1 Hz), 4.66 (d,
1H, J=11.1 Hz), 4.65 (d, 1H, J=12.1 Hz), 4.60 (d, 1H, J=3.4 Hz), 4.56
(d, 1H, J=11.6 Hz), 4.46 (d, 1H, J=11.1 Hz), 4.38 (d, 1H, J=14.0 Hz),
4.32 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 4.23 (d, 1H, J=14.0 Hz), 4.18 (dd,
1H, J=1.9 Hz, J=9.7 Hz), 4.03 (dd, 1H, J=1.9 Hz, J=11.1 Hz), 3.99
(dd, 1H, J=9.2 Hz, J=9.2 Hz), 3.75 (ddd, 1H, J=1.9 Hz, J=4.3 Hz, J=
9.2 Hz), 3.65 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=11.6 Hz), 3.48–3.59 (m,
3H), 3.34–3.40 (m, 4H), 2.27 (ddd, 1H, J=1.9 Hz, J=4.8 Hz, J=
12.6 Hz), 1.67 (ddd, 1H, J=9.7 Hz, J=11.6 Hz, J=12.6 Hz,), 1.31 ppm
(d, 3H, J=6.3 Hz); 13C NMR (100 MHz, CDCl3): d=138.8, 138.6, 138.2,
137.2, 128.9, 128.8, 128.7, 128.6, 128.5, 128.5, 128.2, 128.2, 128.1, 128.1,
128.0, 127.9, 127.8, 127.7, 99.5, 98.1, 84.1, 82.2, 76.0, 75.8, 74.8, 73.4, 70.6,
70.2, 69.6, 67.8 57.5, 55.3, 36.3, 17.8 ppm; IR (solid) n˜ =3029, 2932, 1496,
9a: A mixture of 8 (19.0 mg, 75.3 mmol), 7a (60.6 mg, 113 mmol) and
pulverized activated MS-4ꢁ (113 mg) in dry CH2Cl2 (1.13 mL) was
stirred at RT for 30 min under argon to remove a trace amount of water.
A mixture of 1.00m IBr in CH2Cl2 (151 mL, 151 mmol) and tetrabutylam-
monium bromide (60.7 mg, 188 mmol) was then added to the reaction
mixture at 08C. After being stirred for 2 h, N,N-diisopropylethylamine
(6.58 mL, 37.7 mmol) was added to the reaction mixture at the same tem-
perature. After being stirred for 18 h, the reaction mixture was filtered
through Celite. The filtrate was poured into a mixture of saturated aq.
NaHCO3 and saturated aq. Na2S2O3 with cooling. The aqueous layer was
extracted with two portions of ethyl acetate. The combined extract was
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel with hexane/ethyl
acetate 70:30 and further purified by gel permeation chromatography
(GPC) to give 9a (41.1 mg, 65.6 mmol, 87%, a/b=93:7). The a,b isomers
were separated by chromatographed on silica gel with toluene/ethyl ace-
tate 85:15. The b/a ratio was determined by 1H NMR analysis
(400 MHz). a-9a: ½aꢁ2D4 =+45.38 (c=1.17, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7.22–7.35 (m, 15H), 5.42 (d, 1H, J=3.4 Hz), 4.75 (d, 1H, J=
3.4 Hz), 4.62 (d, 1H, J=11.6 Hz), 4.58 (d, 1H, J=11.6 Hz), 4.42 (d, 1H,
J=11.6 Hz), 4.40 (d, 1H, J=11.6 Hz), 4.36 (d, 1H, J=14.0 Hz), 4.35 (dd,
1H, J=9.2 Hz, J=9.2 Hz), 4.22 (d, 1H, J=14.0 Hz), 3.91–3.99 (m, 2H),
3.85 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=11.1 Hz), 3.67 (dq, 1H, J=
6.3 Hz, J=9.2 Hz), 3.33 (s, 3H), 3.31 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 2.29
(dd, 1H, J=4.8 Hz, J=12.6 Hz), 2.24 (dd, 1H, J=4.8 Hz, J=12.1 Hz),
1.63 (ddd, 1H, J=3.4 Hz, J=11.1 Hz, J=12.6 Hz), 1.60 (ddd, 1H, J=
3.4 Hz, J=11.6 Hz, J=12.1 Hz), 1.28 (d, 3H, J=6.3 Hz), 1.27 ppm (d,
3H, J=6.3 Hz); 13C NMR (100 MHz, CDCl3): d=138.4, 137.7, 128.8,
128.7, 128.6, 128.5, 128.2, 128.0, 127.9, 127.8, 127.7, 98.3, 98.2, 84.8, 81.6,
77.8, 74.4, 71.0, 70.8, 66.6, 66.4, 57.4, 54.7, 35.6, 35.2, 18.6, 17. ppm; IR
(solid): n˜ =2935, 2905, 1455, 1360, 1173, 1098, 1050, 995 cmꢀ1; HRMS
(ESI-TOF) calcd for C34H42O9S [M+Na]+ m/z=649.2447, found:
649.2452; b-9a: ½aꢁ2D2 =+38.08 (c=1.01, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7.21–7.36 (m, 15H), 4.65–4.73 (m, 4H), 4.61 (d, 1H, J=
11.6 Hz), 4.46 (d, 1H, J=11.1 Hz), 4.37 (d, 1H, J=14.0 Hz), 4.35 (dd,
1454, 1356, 1073, 994, 941, 697 cmꢀ1
.
11b: According to the method for the synthesis of 9a, a mixture of 10b
(22.5 mg, 84.0 mmol), 7a (68.2 mg, 127 mmol), and MS-4ꢁ (127 mg) in
CH2Cl2 (1.68 mL) was treated with a mixture of 1.00m IBr in CH2Cl2
(168 mL, 168 mmol) and TBAB (67.6 mg, 210 mmol) at 08C for 2 h. N,N-
Diisopropylethylamine (7.31 mL, 42.0 mmol) was then added to the reac-
tion mixture. After being stirred for 16 h at the same temperature, to
give 11b (46.3 mg, 72.2 mmol, 86%, b/a=8:92) after purification. The a,b
isomers were separated by chromatography on silica gel with toluene/
ethyl acetate 92:8. a-11b: ½aꢁ2D4 =+26.38 (c=1.04, CHCl3); 1H NMR
(400 MHz, CDCl3): d=8.05 (d, 2H, J=7.2 Hz), 7.19–7.60 (m, 13H), 4.97
(dd, 1H, J=9.7 Hz, J=9.7 Hz), 4.95 (d, 1H, J=3.9 Hz), 4.79 (d, 1H, J=
3.4 Hz), 4.48 (d, 1H, J=11.1 Hz), 4.35 (d, 1H, J=11.1 Hz), 4.30 (d, 1H,
J=14.0 Hz), 4.29 (dd, 1H, J=9.7 Hz, J=9.7 Hz), 4.19 (d, 1H, J=
14.0 Hz), 4.14 (ddd, 1H, J=5.3 Hz, J=9.7 Hz, J=11.6 Hz), 3.84–4.00 (m,
3H), 3.36 (s, 3H), 2.21 (dd, 1H, J=12.6 Hz, J=5.3 Hz), 2.07 (dd, 1H, J=
4.8 Hz, J=12.6 Hz), 1.87 (ddd, 1H, J=3.4 Hz, J=11.6 Hz, J=12.6 Hz),
1.45 (ddd, 1H, J=3.9 Hz, J=11.1 Hz, J=12.6 Hz), 1.28 (d, 3H, J=
6.3 Hz), 1.23 ppm (d, 3H, J=6.3 Hz); 13C NMR (100 MHz, CDCl3): d=
165.8, 137.5, 133.5, 130.6, 129.8, 129.6, 128.8, 128.7, 128.6, 128.1, 127.9,
98.7, 98.2, 84.7, 74.8, 73.9, 70.6, 66.3, 65.9, 57.3, 54.9, 37.2, 35.6, 17.8,
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1119

H. Tanaka, T. Takahashi et al.
FULL PAPERS
17.7 ppm; IR (solid): n˜ =3065, 3035, 2936, 1717, 1495, 1453, 1357, 1271,
(29.9 mg, 39.0 mmol, 83%, b/a=10:90) after purification. The a,b isomers
were separated by chromatography on silica gel with toluene. a-11d:
½aꢁ2D4 =+46.08 (c=0.740, CHCl3); 1H NMR (400 MHz, CDCl3): d=7.20–
7.40 (m, 10H), 5.35 (m, 1H), 5.07 (d, 1H, J=3.4 Hz), 4.70 (d, 1H, J=
11.1 Hz), 4.50 (d, 1H, J=11.1 Hz), 4.39 (dd, 1H, J=9.7 Hz, J=9.7 Hz),
4.36 (d, 1H, J=13.5 Hz), 4.23 (d, 1H, J=13.5 Hz), 4.09 (ddd, 1H, J=
5.3 Hz, J=9.7 Hz, J=11.6 Hz), 3.94 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.43
(m, 1H), 2.39 (dd, 1H, J=5.3 Hz, J=12.6 Hz), 2.21–2.36 (m, 2H), 0.84–
2.03 (m, 42H), 0.68 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=140.7,
137.8, 130.6, 128.7, 128.6, 128.2, 128.0, 127.9, 122.0, 94.6, 85.1, 76.6, 76.5,
74.5, 70.8, 66.0, 57.4, 56.9, 56.3, 50.2, 42.4, 40.1, 39.9, 39.6, 37.1, 36.8, 36.3,
36.0, 35.9, 32.0, 29.8, 28.3, 28.1, 27.8, 24.4, 23.9, 22.9, 22.6, 21.2, 19.5, 18.8,
17.8, 12.0 ppm; IR (solid): n˜ =2933, 1455, 1374, 1352, 1168, 1124, 1097,
997 cmꢀ1. b-11d: ½aꢁD21 =ꢀ30.08 (c=0.150, CHCl3); 1H NMR (400 MHz,
CDCl3): d=7.23–7.44 (m, 10H), 5.35 (m, 1H), 4.71 (d, 1H, J=11.6 Hz),
4.61 (dd, 1H, J=1.4 Hz, J=9.7 Hz), 4.48 (d, 1H, J=11.6 Hz), 4.38 (d,
1H, J=14.0 Hz), 4.36 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 4.24 (d, 1H, J=
14.0 Hz), 3.75 (ddd, 1H, J=5.3 Hz, J=9.2 Hz, J=11.6 Hz), 3.55 (m, 1H),
3.45 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 2.44 (ddd, 1H, J=1.4 Hz, J=5.3 Hz,
J=12.6 Hz), 2.19–2.34 (m, 2H), 0.84–2.03 (m, 42H), 0.68 ppm (s, 3H);
13C NMR (100 MHz, CDCl3): d=140.7, 137.3, 130.7, 128.8, 128.8, 128.7,
128.2, 128.1, 122.1, 97.3, 76.3, 70.6, 70.2, 57.6, 56.9, 56.3, 50.3, 42.4, 39.9,
39.6, 38.9, 37.4, 37.2, 36.9, 36.3, 35.9, 32.1, 32.0, 29.8, 29.7, 28.3, 28.1, 24.4,
23.9, 22.9, 22.6, 21.1, 19.4, 18.8, 18.0, 12.0 ppm; IR (solid): n˜ =2925, 2852,
996, 892, 832, 790, 755, 708, 620 cmꢀ1; HRMS (ESI-TOF) calcd for
25
C34H40O10S [M+Na]+ m/z=663.2234, found: 663.2239. b-11b: ½aꢁD
=
1
+4.28 (c=1.00, CHCl3); H NMR (400 MHz, CDCl3): d=8.06 (d, 2H, J=
7.2 Hz), 7.16–7.54 (m, 13H), 4.91 (dd, 1H, J=9.7 Hz, J=9.7 Hz), 4.82 (d,
1H, J=2.9 Hz), 4.61 (d, 1H, J=11.1 Hz), 4.52 (dd, 1H, J=1.4 Hz, J=
9.7 Hz), 4.38 (d, 1H, J=11.1 Hz), 4.31 (d, 1H, J=13.5 Hz), 4.27 (ddd,
1H, J=4.8 Hz, J=9.7 Hz, J=11.6 Hz), 4.16 (d, 1H, J=13.5 Hz), 4.15
(dd, 1H, J=9.2 Hz, J=9.2 Hz), 3.91 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.66
(ddd, 1H, J=5.3 Hz, J=9.2 Hz, J=12.1 Hz), 3.38 (s, 3H), 3.32 (dq, 1H,
J=6.3 Hz, J=9.2 Hz), 2.33 (ddd, 1H, J=1.4 Hz, J=5.3 Hz, J=12.6 Hz),
2.22 (dd, 1H, J=4.8 Hz, J=12.6 Hz), 1.82 (ddd, 1H, J=2.9 Hz, J=
11.6 Hz, J=12.6 Hz), 1.57 (ddd, 1H, J=9.7 Hz, J=12.1 Hz, J=12.6 Hz),
1.24 (d, 3H, J=6.3 Hz), 1.07 ppm (d, 3H, J=6.3 Hz); 13C NMR
(100 MHz, CDCl3): d=166.1, 137.2, 133.1, 130.6, 130.4, 129.9, 128.8,
128.7, 128.6, 128.3, 128.1, 128.0, 98.2, 96.8, 84.1, 76.0, 75.6, 72.8, 70.3, 70.0,
66.1, 57.4, 54.8, 38.7, 35.9, 17.8, 17.6 ppm; IR (solid): n˜ =3033, 2981, 2916,
1722, 1496, 1454, 1353, 1271, 1049, 977, 863, 697 cmꢀ1; HRMS (ESI-TOF)
calcd for C34H40O10S [M+Na]+ m/z=663.2234, found: 663.2231.
11c: According to the method for the synthesis of 9a, a mixture of 11c
(27.6 mg, 58.9 mmol), 7a (47.0 mg, 87.6 mmol), and MS-4ꢁ (87.6 mg) in
CH2Cl2 (1.17 mL) was treated with a mixture of 1.00m IBr in CH2Cl2
(117 mL, 117 mmol) and TBAB (47.0 mg, 146 mmol) at 08C for 2 h. N,N-
Diisopropylethylamine (5.08 mL, 29.2 mmol) was then added to the reac-
tion mixture. After being stirred for 20 h at the same temperature, to 11c
(46.3 mg, 72.2 mmol, 86%, b/a=8:92) after purification. The a,b isomers
were separated by chromatography on silica gel with toluene/ethyl ace-
tate 92:8. a-11c: ½aꢁ2D6 =+38.58 (c=0.400, CHCl3); 1H NMR (400 MHz,
C6D6): d=7.47 (d, 2H, J=7.2 Hz), 6.99–7.30 (m, 18H), 5.48 (d, 1H, J=
2.9 Hz), 4.83 (d, 1H, J=11.6 Hz), 4.65 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
4.64 (dd, 1H, J=1.9 Hz, J=9.7 Hz), 4.60 (d, 1H, J=11.6 Hz), 4.59 (d,
1H, J=2.9 Hz), 4.41 (d, 1H, J=11.6 Hz), 4.35 (d, 1H, J=11.6 Hz), 4.28
(d, 1H, J=14.0 Hz), 4.05–4.19 (m, 5H), 4.02 (ddd, 1H, J=5.3 Hz, J=
9.2 Hz, J=11.6 Hz), 3.94 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.55 (dd, 1H,
J=9.2 Hz, J=9.2 Hz), 3.36–3.42 (m, 2H), 3.22 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.14 (s, 3H), 2.22–2.33 (m, 3H), 1.68–1.76 (m, 2H), 1.49 (d, 3H,
J=5.8 Hz), 1.40–1.46 (m, 4H), 1.35 ppm (d, 3H, J=6.3 Hz); 13C NMR
(100 MHz, CDCl3): d=139.1, 138.1, 137.7, 130.6, 128.8, 128.7, 128.6,
128.6, 128.3, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 100.1, 98.2, 98.1, 84.7,
83.2, 80.9, 79.7, 75.8, 74.3, 72.1, 71.0, 70.8, 70.7, 66.8, 66.6, 57.4, 54.6, 36.7,
35.8, 35.6, 18.7, 18.4, 17.6 ppm; IR (solid): n˜ =3026, 2932, 2879, 1451,
1734, 1455, 1375, 1351, 1175, 1098, 996 cmꢀ1
.
2: 1.00m l-Selectride in THF (363 mL, 363 mmol) was added to a stirred
solution of 1 (100 mg, 91.0 mmol) in THF (1.00 mL) at ꢀ788C. After
being stirred at the same temperature for 30 min, the reaction mixture
was warmed to room temperature. One drop of acetic acid was then
added to the reaction mixture. The reaction mixture was poured into a
mixture of 5% aq. NaHCO3 and 5% aq. NaBO3·4H2O. After being
stirred at RT for 2 h, the aqueous layer was neutralized with 1m HCl at
08C and extracted with two portions of ethyl acetate. The combined ex-
tract was washed with brine, dried over MgSO4, filtered, and concentrat-
ed in vacuo. The residue was chromatographed on silica gel with CHCl3/
methanol 94:6 to give 2 (89.1 mg, 80.9 mmol, 89%). ½aꢁ2D4 =ꢀ37.78 (c=
0.435, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.82 (brs, 1H), 5.27 (s,
1H), 5.08 (d, 1H, J=10.1 Hz), 5.06 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.96
(d, 1H, J=3.4 Hz), 4.81 (dd, 1H, J=1.4 Hz, J=9.2 Hz), 4.11 (m, 1H),
4.08 (m, 1H), 3.92 (brs, 1H), 3.76–3.88 (m, 2H), 3.69 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.55–3.66 (m, 2H), 3.49 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=
11.6 Hz), 3.42 (m, 1H), 3.40 (s, 3H), 3.31 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
3.28 (dd, 1H, J=2.9 Hz, J=9.2 Hz), 3.22–3.27 (m, 2H), 2.87 (dd, 1H, J=
10.1 Hz, J=10.1 Hz), 2.84 (s, 1H), 2.54 (q, 1H, J=7.2 Hz), 2.39 (m, 1H),
2.25–2.35 (m, 2H), 2.23 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.00–2.17 (m,
7H), 1.95 (m, 1H), 1.86 (dd, 1H, J=8.2 Hz, J=14.0 Hz), 1.79 (m, 1H),
1.53–1.72 (m, 15H), 1.23–1.31 (m, 8H), 1.21 (d, 3H, J=6.3 Hz), 1.11 (m,
1H), 1.05 (d, 3H, J=7.2 Hz), 1.02 (s, 3H), 0.88–0.97 (m, 12H), 0.84 (d,
3H, J=7.2 Hz), 0.66 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=
205.4, 203.4, 166.5, 140.1, 135.3, 135.2, 133.1, 127.5, 121.4, 103.1, 100.5,
99.2, 98.5, 91.4, 87.3, 81.3, 80.7, 78.3, 73.2, 70.7, 70.6, 69.3, 68.4, 68.3, 67.8,
65.0, 61.1, 57.5, 57.4, 48.8, 43.6, 42.0, 41.8, 38.2, 38.0, 37.4, 36.7, 35.7, 35.2,
35.1, 34.9, 33.1, 32.2, 32.0, 31.1, 29.8, 29.0, 23.7, 23.2, 23.1, 22.0, 21.5, 20.5,
20.4, 19.3, 18.1, 17.8, 17.3, 14.8, 12.7 ppm; IR (solid): n˜ =3445, 2962, 2928,
1744, 1626, 1455, 1380, 1124, 1058, 1014, 988 cmꢀ1; HRMS (ESI-TOF)
calcd for C61H96O17 [M+Na]+ m/z=1123.6545, found: 1123.6541.
1352, 1161, 1088, 1042, 932, 751, 695 cmꢀ1; HRMS (ESI-TOF) calcd for
24
C47H58O12S [M+Na]+ m/z=869.3541, found: 869.3562. b-11c: ½aꢁD
=
1
+32.08 (c=1.23, CHCl3); H NMR (400 MHz, C6D6): d=7.50 (d, 2H, J=
7.2 Hz), 7.44 (d, 2H, J=7.2 Hz), 7.04–7.30 (m, 16H), 4.93 (d, 1H, J=
11.6 Hz), 4.53–4.69 (m, 6H), 4.46 (dd, 1H, J=1.4 Hz, J=9.7 Hz), 4.28 (d,
1H, J=11.1 Hz), 4.23 (d, 1H, J=13.5 Hz), 4.16 (d, 1H, J=13.5 Hz), 4.09
(ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=11.1 Hz), 4.07 (d, 1H, J=11.1 Hz),
3.92 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.55 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
3.47 (ddd, 1H, J=5.3 Hz, J=9.2 Hz, J=11.6 Hz), 3.38 (dd, 1H, J=
9.2 Hz, J=9.2 Hz), 3.26–3.35 (m, 2H), 3.14 (dq, 1H J=5.8 Hz, J=
9.7 Hz), 3.13 (s, 3H), 2.37 (ddd, 1H, J=1.4 Hz, J=5.3 Hz, J=12.6 Hz),
2.26 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.18 (ddd, 1H, J=1.4 Hz, J=
5.3 Hz, J=12.6 Hz), 1.87 (ddd, 1H, J=9.7 Hz, J=11.6 Hz, J=12.6 Hz),
1.73 (ddd, 1H, J=3.9 Hz, J=11.1 Hz, J=13.0 Hz), 1.63 (ddd, 1H, J=
9.7 Hz, J=11.6 Hz, J=12.6 Hz), 1.44 (d, 3H, J=5.8 Hz), 1.40 (d, 3H, J=
6.3 Hz), 1.34 ppm (d, 3H, J=6.3 Hz); 13C NMR (100 MHz, CDCl3): d=
139.1, 138.6, 137.3, 130.6, 128.9, 128.8, 128.7, 128.4, 128.3, 128.2, 128.0,
127.7, 127.5, 127.4, 100.2, 99.9, 98.2, 84.0, 83.2, 82.9, 77.6, 76.1, 75.9, 72.1,
71.9, 71.2, 70.7, 70.3, 66.7, 57.5, 54.6, 37.5, 36.9, 35.8, 18.4, 18.2, 17.9 ppm;
IR (neat): n˜ =2934, 1497, 1455, 1357, 1158, 1103, 1053, 989, 738,
12: N,N,N’,N’-Tetramethylenediamine (300 mL), acetic anhydride
(150 mL), and a catalytic amount of DMAP (2.00 mg, 16.2 mmol) were
added to a stirred solution of 2 (89.1 mg, 80.9 mmol) in CH2Cl2 (1.00 mL)
at 08C. After being stirred at RT for 3 h, the reaction mixture was
poured into saturated aq. NH4Cl. The aqueous layer was extracted with
two portions of ethyl acetate. The combined extract was washed with sa-
turated aq. NaHCO3 and brine, dried over MgSO4, filtered, and concen-
697 cmꢀ1 HRMS (ESI-TOF) calcd for C47H58O12S [M+Na]+ m/z=
;
869.3541, found: 869.3531.
11d: According to the method for the synthesis of 9a, 11d (18.2 mg,
47.0 mmol), 7a (37.8 mg, 70.5 mmol), and MS-4ꢁ (70.5 mg) in CH2Cl2
(0.940 mL) were treated with a mixture of 1.00m IBr in CH2Cl2 (94.0 mL,
94.0 mmol) and TBAB (37.9 mg, 118 mmol) at 08C for 2 h. N,N-Diisopro-
pylethylamine (4.09 mL, 23.5 mmol) was then added to the reaction mix-
ture. After being stirred for 15 h at the same temperature, to 11d
trated in vacuo. The residue was chromatographed on silica gel with
25
hexane/ethyl aetate 60:40 to give 12 (121 mg, 72.7 mmol, 90%). ½aꢁD
=
1
+1.628 (c=1.00, CHCl3); H NMR (400 MHz, CDCl3): d=5.44 (brs, 1H),
5.42 (m, 1H), 5.32 (s, 1H), 5.24 (m, 1H), 5.10 (brs, 1H), 5.05 (dd, 1H,
J=1.9 Hz, J=9.7 Hz), 4.98 (d, 1H, J=9.7 Hz), 4.90 (d, 1H, J=3.4 Hz),
4.90 (ddd, 1H, J=4.8 Hz, J=10.6 Hz, J=10.6 Hz), 4.65 (brd, 1H, J=
1120
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Efficient Synthesis of Deoxysugar Part of Versipelostatin
8.7 Hz), 4.54 (dd, 1H, J=2.9 Hz, J=9.7 Hz), 4.16 (dd, 1H, J=2.9 Hz, J=
11.1 Hz), 3.88 (dq, 1H, J=9.7 Hz, J=6.3 Hz), 3.82 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.63 (dd, 1H, J=8.7 Hz, J=11.1 Hz), 3.56 (dq, 1H, J=
6.3 Hz, J=9.2 Hz), 3.44 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=11.6 Hz), 3.37
(s, 3H, Me), 3.21–3.28 (m, 3H), 3.03 (s, 1H), 2.83 (dd, 1H, J=10.6 Hz,
J=10.6 Hz), 2.65 (q, 1H, J=7.7 Hz), 2.59 (m, 1H), 2.41 (m, 1H), 2.28–
2.37 (m, 2H), 2.23 (dd, 1H, J=4.8 Hz, J=12.6 Hz), 2.12–2.21 (m, 2H),
2.12 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.05 (m, 1H), 2.00 (s,
3H), 1.87–1.99 (m, 7H), 1.78–1.84 (m, 2H), 1.75 (m, 1H), 1.64–1.72 (m,
6H), 1.15–1.62 (m, 20H), 1.03–1.09 (m, 12H), 0.99 (t, 3H, J=7.7 Hz),
0.90 (d, 3H, J=6.8 Hz), 0.74 (d, 3H, J=6.8 Hz), 0.70 ppm (m, 1H);
13C NMR (67.8 MHz, CDCl3): d=205.1, 202.1, 170.9, 170.7, 170.4, 170.3,
170.1, 166.6, 140.0, 135.9, 135.5, 133.8, 126.6, 120.4, 103.3, 99.8, 99.8, 98.7,
90.3, 87.3, 81.8, 79.9, 78.6, 74.8, 73.1, 72.8, 70.7, 69.1, 68.0, 67.8, 66.7, 60.9,
57.3, 45.3, 41.4, 41.1, 37.3, 36.1, 35.4, 35.0, 34.7, 33.4, 32.8, 31.5, 30.4, 30.0,
23.8, 22.6, 21.6, 21.3, 21.1, 21.0, 20.9, 20.8, 19.5, 19.3, 18.2, 17.9, 16.9, 14.0,
12.5 ppm; IR (neat): n˜ =2971, 2936, 1743, 1450, 1372, 1244, 1059, 1018,
2.9 Hz, J=11.1 Hz), 3.87 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.69–3.75 (m,
2H), 3.23 (brd, 1H, J=6.8 Hz), 2.26–2.85 (m, 11H), 2.18 (s, 3H), 2.10 (s,
3H), 2.10 (s, 3H), 2.07 (m, 1H), 2.03 (s, 3H), 1.97 (s, 3H), 1.71–1.96 (m,
7H), 1.68 (s, 3H), 1.67 (m, 1H), 1.20–1.63 (m, 20H), 1.19 (d, 3H, J=
6.3 Hz), 1.10 (s, 3H), 1.09 (d, 3H, J=6.3 Hz), 1.07 (t, 3H, J=7.7 Hz),
1.00 (t, 3H, J=7.2 Hz), 0.98 (d, 3H, J=7.2 Hz), 0.92 (d, 3H, J=6.3 Hz),
0.90 (d, 3H, J=6.3 Hz), 0.85 ppm (m, 1H); 13C NMR (100 MHz, CDCl3):
d=206.4, 181.2, 171.9, 171.7, 171.0, 170.4, 170.1, 167.9, 140.4, 135.7, 135.5,
135.2, 126.6, 120.7, 116.2, 99.6, 90.7, 87.9, 76.6, 73.0, 72.9, 72.5, 68.1, 68.0,
65.9, 61.3, 61.2, 57.5, 41.9, 39.6, 39.2, 38.0, 37.0, 36.0, 34.6, 34.1, 33.7, 33.1,
32.9, 30.9, 30.7, 29.8, 29.7, 28.8, 27.9, 26.8, 23.4, 22.8, 22.0, 21.6, 21.3, 21.2,
21.1, 21.0, 20.9, 20.0, 19.3, 18.9, 18.5, 17.9, 16.3, 13.9, 11.5 ppm; IR (neat):
n˜ =2927, 1787, 1741, 1370, 1244, 1157, 1065, 1036 cmꢀ1; HRMS (ESI-
TOF) calcd for C66H96O18 [M+Na]+ m/z=1199.6494, found: 1199.6498.
16: Acetic acid (361 mL) and hydrazine monohydrate (11.6 mL, 241 mmol)
were added to a stirred solution of 15 (28.8 mg, 24.1 mmol) in pyridine
(180 mL) at 08C. After being stirred at RT for 3 h, the reaction mixture
was poured into a saturated aq. NaHCO3. The aqueous layer was extract-
ed with two portions of ethyl acetate. The combined extract was washed
with 1m HCl, saturated aq. NaHCO3, and brine, dried over MgSO4, fil-
tered, and concentrated in vacuo. The residue was chromatographed on
silica gel with hexane/ethyl aetate 50:50 to give 16 (23.2 mg, 21.5 mmol,
90%). ½aꢁ2D2 =ꢀ8.248 (c=1.17, CHCl3); 1H NMR (400 MHz, CDCl3): d=
5.42 (brs, 1H), 5.40 (s, 1H), 5.25–5.27 (m, 2H), 5.14 (d, 1H, J=9.7 Hz),
4.77 (m, 1H), 4.70 (dd, 1H, J=1.0 Hz, J=9.7 Hz), 4.10 (dd, 1H, J=
2.4 Hz, J=10.6 Hz), 3.72 (dd, 1H, J=7.2 Hz, J=10.6 Hz), 3.71 (brs, 1H),
3.64 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.41 (m, 1H), 3.22 (dd, 1H, J=
1.9 Hz, J=7.2 Hz), 2.59 (m, 1H), 2.26–2.56 (m, 6H), 2.15 (ddd, 1H, J=
1.0 Hz, J=2.9 Hz, J=14.4 Hz), 2.13 (s, 3H), 2.11 (s, 3H), 2.03 (s, 3H),
1.97 (s, 3H), 1.71–1.97 (m, 8H), 1.69 (s, 3H), 1.66 (m, 1H), 1.58 (s, 3H),
1.22–1.58 (m, 20H), 1.10 (s, 3H), 1.08 (d, 3H, J=6.3 Hz), 1.06 (t, 3H, J=
7.7 Hz), 1.00 (t, 3H, J=7.7 Hz), 0.98 (d, 3H, J=6.8 Hz), 0.91 (d, 3H, J=
6.3 Hz), 0.90 (d, 3H, J=6.3 Hz), 0.85 ppm (m, 1H); 13C NMR (100 MHz,
CDCl3): d=198.1, 181.2, 171.7, 171.2, 171.0, 170.6, 170.4, 167.6, 140.4,
135.6, 135.5, 135.1, 126.6, 120.7, 116.1, 99.5, 90.5, 87.9, 72.9, 72.6, 72.2,
71.7, 70.2, 66.0, 60.4, 57.4, 53.4, 41.9, 39.5, 39.0, 36.9, 36.0, 34.6, 34.1, 33.8,
33.1, 32.9, 30.8, 30.6, 29.7, 28.9, 26.7, 23.3, 22.8, 21.9, 21.6, 21.2, 21.1, 21.0,
20.9, 19.9, 19.2, 18.9, 18.6, 18.1, 16.3, 14.2, 13.8, 11.4 ppm; IR (neat): n˜ =
3458, 2962, 2933, 1788, 1681, 1372, 1241, 1216, 1066, 1023 cmꢀ1; HRMS
(ESI-TOF) calcd for C61H90O16 [M+Na]+ m/z=1101.6127, found:
1101.6177.
988 cmꢀ1
;
HRMS (ESI-TOF) calcd for C73H108O23 [M+Na]+ m/z=
1375.7179, found: 1375.7190.
3: N,N,N’,N’-Tetramethylenediamine (200 mL), pivaloyl chloride (100 mL),
and DMAP (8.88 mg, 72.7 mmol) were added to a stirred solution of 9
(121 mg, 72.7 mmol) in CH2Cl2 (1.00 mL) at RT. After being stirred under
reflux for 12 h, the reaction mixture was poured into a saturated aq.
NaHCO3. The aqueous layer was extracted with two portions of ethyl
acetate. The combined extract was washed with saturated brine, dried
over MgSO4, filtered, and concentrated in vacuo. The residue was used
for the next reaction without further purification. To a stirred solution of
the residue in CH2Cl2 (0.900 mL) and methanol (0.100 mL) was added
trifluoroacetic acid (0.250 mL) at RT. After being stirred at room temper-
ature for 1 h, the reaction mixture was concentrated in vacuo. The resi-
due was chromatographed on silica gel with hexane/ethyl acetate 60:40
and further purified by gel permeation chromatography (GPC) to give 3
(56.0 mg, 61.7 mmol, 2 steps, 85%). ½aꢁ2D7 =ꢀ25.18 (c=0.960, CHCl3);
1H NMR (400 MHz, CDCl3): d=5.46 (brs, 1H), 5.42 (s, 1H), 5.28 (m,
1H), 5.18 (d, 1H, J=9.2 Hz), 4.74 (ddd, 1H, J=7.7 Hz, J=10.6 Hz, J=
10.6 Hz), 4.08 (dd, 1H, J=2.9 Hz, J=10.6 Hz), 3.81 (s, 1H), 3.77 (dd,
1H, J=6.8 Hz, J=10.6 Hz), 3.11 (brd, 1H, J=8.2 Hz), 2.63 (dd, 1H, J=
8.7 Hz, J=14.5 Hz), 2.61 (m, 1H), 2.31–2.47 (m, 4H), 2.17 (m, 1H), 2.10
(s, 3H), 2.02 (s, 3H), 2.00 (s, 3H), 1.96 (q, 1H, J=7.7 Hz), 1.92 (m, 1H),
1.89 (q, 1H, J=7.7 Hz), 1.82 (q, 1H, J=7.7 Hz), 1.73–1.82 (m, 2H), 1.69
(s, 3H), 1.58 (s, 3H), 1.17–1.55 (m, 18H), 1.12 (s, 3H), 1.08 (t, 3H, J=
6.3 Hz), 1.07 (d, 3H, J=6.3 Hz), 0.99 (t, 3H, J=7.7 Hz), 0.97 (d, 3H, J=
7.2 Hz), 0.97 (d, 3H, J=7.2 Hz), 0.94 (d, 3H, J=6.8 Hz), 0.88 ppm (m,
1H); 13C NMR (100 MHz, CDCl3): d=198.9, 180.7, 171.7, 171.2, 170.6,
170.4, 167.7, 140.5, 135.7, 135.3, 135.2, 126.3, 120.9, 115.8, 88.0, 82.0, 72.9,
71.8, 65.6, 61.9, 57.3, 41.5, 39.8, 37.1, 35.5, 34.5, 34.0, 33.6, 32.3, 31.1, 30.3,
29.7, 26.6, 26.5, 23.5, 22.9, 22.2, 21.7, 21.3, 21.2, 21.1, 20.9, 20.2, 19.1, 18.3,
16.5, 14.0, 11.2 ppm; IR (solid): n˜ =3529, 2935, 2875, 1789, 1739, 1681,
1588, 1458, 1374, 1239, 1100, 1063, 969 cmꢀ1; HRMS (ESI-TOF) calcd for
C53H78O12 [M+H]+ m/z=907.5572, found: 907.5596.
17: A mixture of 16 (26.3 mg, 24.3 mmol), 5 (31.7 mg, 60.9 mmol) and
pulverized activated MS-4ꢁ (48.7 mg) in dry CH2Cl2 (490 mL) was stirred
at RT for 30 min under argon to remove a trace amount of water. A mix-
ture of 1.00m IBr in CH2Cl2 (73.1 mL, 73.1 mmol) and tetrabutylammoni-
um bromide (31.4 mg, 97.5 mmol) was then added to the reaction mixture
at 08C. After being stirred for 2 h, N,N-diisopropylethylamine (2.10 mL,
12.2 mmol) was added to the reaction mixture at the same temperature.
After being stirred for 24 h, the reaction mixture was filtered through
Celite. The filtrate was poured into a mixture of saturated aq. NaHCO3
and saturated aq. Na2S2O3 with cooling. The aqueous layer was extracted
with two portions of ethyl acetate. The combined extract was washed
with brine, dried over MgSO4, filtered, and concentrated in vacuo. The
residue was chromatographed on silica gel with hexane/ethyl acetate
50:50 and further purified by gel permeation chromatography (GPC) to
give 17 (26.2 mg, 18.3 mmol, 75%, a/b=95:5). The b/a ratio was deter-
mined by 1H NMR analysis (400 MHz). ½aꢁD22 =+9.458 (c=0.600, CHCl3);
1H NMR (400 MHz, CDCl3): d=8.20 (d, 2H, J=8.7 Hz), 7.40 (d, 2H, J=
8.7 Hz), 5.50 (m, 1H), 5.43 (brs, 1H), 5.39 (s, 1H), 5.25 (m, 1H), 5.15 (d,
1H, J=9.7 Hz), 5.09 (d, 1H, J=3.4 Hz), 4.78 (m, 1H), 4.78 (d, 1H, J=
9.7 Hz), 4.20 (dd, 1H, J=9.7 Hz, J=9.7 Hz), 4.11 (dd, 1H, J=2.9 Hz, J=
11.1 Hz), 3.81 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.77 (dq, 1H, J=6.3 Hz,
J=9.7 Hz), 3.70–3.75 (m, 2H), 3.48–3.63 (m, 3H), 3.38 (dd, 1H, J=
2.9 Hz, J=9.7 Hz), 3.23–3.32 (m, 6H), 2.59 (m, 1H), 2.54 (m, 1H), 2.49
(m, 1H), 2.44 (q, 1H, J=7.7 Hz), 2.31–2.40 (m, 3H), 2.15 (dd, 1H, J=
5.3 Hz, J=12.5 Hz), 2.11 (s, 3H), 2.10 (s, 3H), 2.06 (m, 1H), 2.03 (s, 3H),
1.97 (s, 3H), 1.97 (q, 1H, J=7.7 Hz), 1.90 (m, 1H), 1.86 (q, 1H, J=
7.7 Hz), 1.80 (q, 1H, J=7.7 Hz), 1.69–1.80 (m, 3H), 1.69 (s, 3H), 1.68 (m,
1H), 1.20–1.61 (m, 27H), 1.10 (s, 3H), 1.09 (d, 3H, J=6.3 Hz), 1.07 (t,
15: A mixture of 3 (34.0 mg, 37.4 mmol), 4 (40.5 mg, 93.7 mmol), and pulv-
erized activated MS-4ꢁ (56.0 mg) in dry toluene (0.560 mL) was stirred
at RT for 30 min under argon to remove a trace amount of water. The re-
action mixture was then cooled to ꢀ948C (hexane–liquid N2 bath). After
5 min, a solution of iodine (28.4 mg, 112.2 mmol) in toluene (0.200 mL)
and triethylsilane (0.600 mL, 3.74 mmol) were added to the reaction mix-
ture. After being stirred for 1.5 h, the reaction mixture was neutralized
with triethylamine at ꢀ948C and filtered through Celite. Immediately the
filtrate was poured into a mixture of saturated aq. NaHCO3 and saturat-
ed aq. Na2S2O3 with cooling. The aqueous layer was extracted with two
portions of ethyl acetate. The combined extract was washed with brine,
dried over MgSO4, filtered, and concentrated in vacuo. The residue was
chromatographed on silica gel with hexane/ethyl acetate 50:50 and fur-
ther purified by gel permeation chromatography (GPC) to give 15
(36.7 mg, 30.7 mmol, 82%, b/a=95:5). The b/a ratio was determined by
1H NMR analysis (400 MHz). ½aꢁD22 =ꢀ4.928 (c=1.25, CHCl3); 1H NMR
(400 MHz, CDCl3): d=5.42 (brs, 1H), 5.41 (m, 1H), 5.40 (s, 1H), 5.24
(m, 1H), 5.15 (d, 1H, J=9.7 Hz), 4.77 (dd, 1H, J=1.0 Hz, J=9.7 Hz),
4.76 (m, 1H), 4.55 (dd, 1H, J=2.9 Hz, J=10.1 Hz), 4.11 (dd, 1H, J=
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1121

H. Tanaka, T. Takahashi et al.
FULL PAPERS
3H, J=7.7 Hz), 1.01 (t, 3H, J=7.7 Hz), 0.99 (d, 3H, J=6.8 Hz), 0.91 (d,
3H, J=6.3 Hz), 0.91 (d, 3H, J=6.3 Hz), 0.86 ppm (m, 1H); 13C NMR
(100 MHz, CDCl3): d=198.2, 181.3, 171.7, 171.0, 170.6, 170.4, 170.2,
167.6, 147.2, 145.4, 140.4, 135.7, 135.5, 135.1, 129.3, 126.6, 124.1, 120.7,
116.2, 99.6, 93.3, 90.7, 87.9, 84.9, 75.4, 74.4, 73.0, 72.6, 68.7, 66.6, 66.0,
65.9, 61.2, 57.5, 51.6, 42.0, 41.2, 39.6, 39.1, 37.0, 36.1, 34.7, 34.2, 34.1, 33.9,
33.2, 32.9, 30.9, 30.6, 29.8, 29.0, 26.8, 23.4, 22.8, 22.0, 21.6, 21.3, 21.2, 21.1,
20.9, 20.0, 19.3, 19.0, 18.8, 18.7, 17.6, 16.4, 13.9, 11.5 ppm; IR (neat): n˜ =
2962, 2933, 1789, 1740, 1681, 1589, 1524, 1369, 1347, 1243, 1097, 1063,
994 cmꢀ1; HRMS (ESI-TOF) calcd for C76H109NO23S [M+Na]+ m/z=
1458.7009, found: 1458.6998.
(67.8 MHz, CDCl3): d=206.5, 198.3, 181.2, 171.9, 171.8, 171.0, 170.6,
170.4, 170.2, 170.1, 167.6, 140.4, 135.7, 135.6, 135.2, 126.6, 120.8, 116.2,
99.7, 99.0, 93.6, 90.7, 87.9, 83.6, 74.1, 73.0, 72.7, 72.5, 70.6, 68.9, 68.3, 67.7,
67.3, 66.1, 66.0, 65.9, 61.3, 57.5, 57.2, 41.9, 39.6, 39.2, 37.9, 36.9, 36.2, 36.1,
34.6, 34.2, 33.7, 33.1, 32.0, 30.9, 30.7, 30.4, 29.9, 29.7, 27.9, 26.8, 23.5, 22.8,
22.7, 22.0, 21.6, 21.3, 21.2, 21.1, 20.9, 20.0, 19.3, 18.8, 18.5, 18.1, 18.0, 16.4,
14.2, 13.4, 11.5 ppm; IR (neat): n˜ =2961, 2930, 1788, 1742, 1681, 1456,
1371, 1242, 1151, 1095, 1067, 1023 cmꢀ1; HRMS (ESI-TOF) calcd for
C81H120O25 [M+Na]+ m/z=1515.8016, found: 1515.8000.
21: NaOMe (20.0 mg) was added to a stirred solution of 20 (5.50 mg,
3.68 mmol) in methanol (500 mL) at RT. After being stirred under reflux
for 24 h, the reaction mixture was neutralized with Dowex 50WX4 and
filtered. The filtrate was poured into saturated aq. NH4Cl. The aqueous
layer was extracted with two portions of ethyl acetate. The combined ex-
tract was washed with brine, dried over MgSO4, filtered, and concentrat-
ed in vacuo. The residue was chromatographed on silica gel with CHCl3/
methanol 94:6 to give 21 (3.00 mg, 2.72 mmol, 75%). ½aꢁ2D4 =+10.78 (c=
0.150, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.82 (brs, 1H), 5.27 (s,
1H), 5.09 (d, 1H, J=10.6 Hz), 4.98–5.01 (m, 2H), 4.82 (dd, 1H, J=
1.4 Hz, J=9.2 Hz), 4.20 (m, 1H), 4.12 (m, 1H), 3.92 (brs, 1H), 3.85 (ddd,
1H, J=4.3 Hz, J=10.6 Hz, J=10.6 Hz), 3.80 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.73 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.73 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.58–3.64 (m, 2H), 3.43 (s, 3H), 3.43 (m, 1H), 3.38 (dd, 1H, J=
2.9 Hz, J=9.2 Hz), 3.31 (dd, 1H, J=2.9 Hz, J=9.2 Hz), 3.23 (m, 1H),
3.22 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 2.86 (dd, 1H, J=10.6 Hz, J=
10.6 Hz), 2.85 (s, 1H), 2.53 (q, 1H, J=7.2 Hz), 2.40 (m, 1H), 2.24–2.35
(m, 2H), 2.19 (m, 1H), 1.98–2.18 (m, 7H), 1.96 (brdd, 1H, J=10.6 Hz,
J=10.6 Hz), 1.86 (dd, 1H, J=14.5 Hz, J=8.2 Hz), 1.80 (m, 1H), 1.78 (m,
1H), 1.53–1.73 (m, 14H), 1.22–1.31 (m, 11H), 1.13 (m, 1H), 1.05 (d, 3H,
J=7.2 Hz), 1.03 (s, 3H), 0.99 (t, 3H, J=7.2 Hz), 0.98 (t, 3H, J=7.2 Hz),
0.96 (d, 3H, J=7.2 Hz), 0.91 (d, 3H, J=6.8 Hz), 0.84 (d, 3H, J=6.8 Hz),
0.66 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=205.5, 203.0, 166.4,
140.2, 135.4, 135.2, 133.1, 127.4, 103.1, 100.7, 98.9, 93.2, 91.6, 87.3, 83.2,
75.7, 73.3, 73.0, 70.7, 70.5, 69.7, 68.4, 68.0, 67.8, 64.9, 64.1, 61.0, 57.5, 57.4,
48.8, 43.6, 42.0, 41.8, 38.2, 38.0, 37.1, 36.8, 35.7, 35.2, 35.1, 34.5, 33.1, 32.2,
31.1, 29.5, 29.1, 23.7, 23.2, 23.0, 22.0, 21.5, 20.6, 20.4, 19.3, 18.4, 18.2, 17.3,
14.8, 12.7 ppm; IR (solid): n˜ =3450, 2930, 2962, 1739, 1625, 1456, 1380,
1261, 1068 cmꢀ1; HRMS (ESI-TOF) calcd for C61H96O17 [M+Na]+ m/z=
1123.6545, found: 1123.6556.
18: DBU (18.0 mL, 121 mmol) was added to a stirred solution of 17
(17.5 mg, 12.1 mmol) in CH3CN (360 mL) at 08C. After being stirred at
RT for 3 h, the reaction mixture was poured into saturated aq. NH4Cl.
The aqueous layer was extracted with two portions of ethyl acetate. The
combined extract was washed with 1m HCl, saturated aq. NaHCO3, and
brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue
was chromatographed on silica gel with hexane/ethyl aetate 40:60 to give
18 (11.4 mg, 9.31 mmol, 77%). ½aꢁ2D6 =+3.538 (c=0.390, CHCl3); 1H NMR
(400 MHz, CDCl3): d=5.51 (m, 1H), 5.42 (brs, 1H), 5.40 (s, 1H), 5.25
(m, 1H), 5.15 (d, 1H, J=9.2 Hz), 5.06 (d, 1H, J=3.4 Hz), 4.77 (m, 1H),
4.77 (dd, 1H, J=1.9 Hz, J=10.1 Hz), 4.11 (dd, 1H, J=2.9 Hz, J=
11.1 Hz), 3.77 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.70–3.75 (m, 2H), 3.67
(dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.42 (dd, 1H, J=2.9 Hz, J=9.7 Hz), 3.38
(m, 1H), 3.36 (s, 3H), 3.16 (dd, 1H, J=1.4 Hz, J=7.2 Hz), 3.15 (dd, 1H,
J=9.7 Hz, J=9.7 Hz), 2.59 (m, 1H), 2.55 (m, 1H), 2.49 (m, 1H), 2.44 (q,
1H, J=7.7 Hz), 2.26–2.38 (m, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.03–2.10
(m, 2H), 2.03 (s, 3H), 1.97 (s, 3H), 1.97 (q, 1H, J=7.7 Hz), 1.90 (m,
1H), 1.88 (q, 1H, J=7.7 Hz), 1.80 (q, 1H, J=7.7 Hz), 1.69–1.78 (m, 3H),
1.68 (s, 3H), 1.67 (m, 1H), 1.18–1.65 (m, 27H), 1.10 (s, 3H), 1.09 (d, 3H,
J=6.3 Hz), 1.07 (t, 3H, J=7.7 Hz), 1.00 (t, 3H, J=7.7 Hz), 0.98 (d, 3H,
J=7.2 Hz), 0.81–0.93 ppm (m, 7H); 13C NMR (100 MHz, CDCl3): d=
198.3, 181.2, 171.8, 171.1, 171.0, 170.6, 170.4, 170.2, 167.6, 140.4, 135.7,
135.6, 135.2, 126.6, 120.8, 116.2, 99.7, 93.8, 90.7, 87.9, 78.2, 76.0, 73.9, 73.0,
72.6, 69.0, 68.3, 66.0, 65.9, 61.3, 57.5, 56.4, 41.9, 39.6, 39.2, 37.0, 36.1, 34.6,
34.2, 33.8, 33.5, 33.1, 33.0, 32.0, 30.9, 30.7, 29.8, 28.8, 26.8, 23.5, 22.8, 22.0,
21.6, 21.3, 21.2, 21.1, 21.1, 20.9, 20.0, 19.3, 18.9, 18.5, 17.8, 16.4, 13.9,
11.4 ppm; IR (neat): n˜ =3483, 2964, 2934, 1789, 1742, 1681, 1589, 1456,
1371, 1241, 1068, 1023, 986 cmꢀ1; HRMS (ESI-TOF) calcd for C68H102O19
[M+Na]+ m/z=1245.6913, found: 1245.6876.
23: A mixture of 16 (24.7 mg, 22.9 mmol), 22 (29.8 mg, 57.2 mmol) and
pulverized activated MS-4ꢁ (40.0 mg) in dry CH2Cl2 (450 mL) was
stirred at RT for 30 min under argon to remove a trace amount of water.
A mixture of 1.00m IBr in CH2Cl2 (68.4 mL, 68.4 mmol) and tetrabuty-
lammonium bromide (29.5 mg, 91.5 mmol) was then added to the reac-
tion mixture at 08C. After being stirred for 2 h, N,N-diisopropylethyla-
mine (2.00 mL, 11.4 mmol) was added to the reaction mixture at the same
temperature. After being stirred for 24 h, the reaction mixture was fil-
tered through Celite. The filtrate was poured into a mixture of saturated
aq. NaHCO3 and saturated aq. Na2S2O3, with cooling. The aqueous layer
was extracted with two portions of ethyl acetate. The combined extract
was washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel with hexane/ethyl
acetate 50:50 and further purified by gel permeation chromatography
(GPC) to give 23 (26.3 mg, 18.3 mmol, 80%, a/b=95:5). The b/a ratio
was determined by 1H NMR analysis (400 MHz). ½aꢁ2D2 =ꢀ10.78 (c=1.15,
CHCl3); 1H NMR (400 MHz, CDCl3): d 8.20 (d, 2H, J=8.2 Hz), 7.39 (d,
2H, J=8.2 Hz), 5.42 (brs, 1H,), 5.39 (s, 1H), 5.22–5.27 (m, 2H), 5.14 (d,
1H, J=9.7 Hz), 4.97 (brd, 1H, J=2.9 Hz), 4.77 (m, 1H), 4.68 (brd, 1H,
J=8.7 Hz), 4.18 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 4.11 (dd, 1H, J=2.9 Hz,
J=11.1 Hz), 3.83 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.81 (dq, 1H, J=
6.3 Hz, J=9.2 Hz), 3.68–3.73 (m, 2H), 3.47–3.65 (m, 3H), 3.26–3.34 (m,
6H), 3.20 (dd, 1H, J=1.9 Hz, J=7.2 Hz), 2.59 (m, 1H), 2.53 (m, 1H),
2.47 (m, 1H), 2.42 (q, 1H, J=7.7 Hz), 2.28–2.40 (m, 4H), 2.16 (m, 1H),
2.12 (s, 3H), 2.10 (s, 3H), 2.03 (s, 3H), 1.97 (s, 3H), 1.96 (q, 1H, J=
7.7 Hz), 1.91 (m, 1H), 1.87 (q, 1H, J=7.7 Hz), 1.82 (q, 1H, J=7.7 Hz),
1.71–1.80 (m, 3H), 1.69 (s, 3H), 1.65 (m, 1H), 1.21–1.62 (m, 27H), 1.10
(s, 3H), 1.07 (d, 3H, J=7.2 Hz), 1.06 (t, 3H, J=7.7 Hz), 1.00 (t, 3H, J=
7.7 Hz), 0.98 (d, 3H, J=7.2 Hz), 0.91 (d, 3H, J=6.3 Hz), 0.88 (d, 3H, J=
6.3 Hz), 0.85 ppm (m, 1H); 13C NMR (67.8 MHz, CDCl3): d=198.2,
20: A mixture of 18 (9.20 mg, 7.52 mmol), 4 (9.80 mg, 22.6 mmol) and
pulverized activated MS-4ꢁ (23.0 mg) in dry toluene (0.225 mL) was
stirred at RT for 30 min under argon to remove a trace amount of water.
The reaction mixture was then cooled to ꢀ948C (hexane–liquid N2 bath).
After 5 min,
a solution of iodine (6.70 mg, 26.3 mmol) in toluene
(50.0 mL) and triisopropylsilane (0.310 mL, 1.51 mmol) were added to the
reaction mixture. After being stirred for 1.5 h, the reaction mixture was
neutralized with triethylamine at ꢀ948C and filtered through Celite. Im-
mediately the filtrate was poured into
a mixture of saturated aq.
NaHCO3 and saturated aq. Na2S2O3 with cooling. The aqueous layer was
extracted with two portions of ethyl acetate. The combined extract was
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo. The residue was chromatographed on silica gel with hexane/ethyl
acetate 50:50 and further purified by gel permeation chromatography
(GPC) to give 20 (8.90 mg, 5.96 mmol, 80%, b/a=94:6). The b/a ratio
was determined by H NMR analysis (400 MHz). ½aꢁ2D6 =+13.48 (c=0.290,
1
CHCl3); 1H NMR (400 MHz, CDCl3): d=5.49 (m, 1H), 5.40–5.43 (m,
3H), 5.25 (m, 1H), 5.15 (d, 1H, J=9.7 Hz), 5.00 (brd, 1H, J=1.9 Hz),
4.97 (dd, 1H, J=1.9 Hz, J=9.7 Hz), 4.73–4.80 (m, 2H), 4.57 (dd, 1H, J=
2.9 Hz, J=9.7 Hz), 4.10 (dd, 1H, J=2.9 Hz, J=10.6 Hz), 3.93 (dq, 1H,
J=6.3 Hz, J=9.7 Hz), 3.70–3.79 (m, 3H), 3.66 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.54 (ddd, 1H, J=4.8 Hz, J=8.2 Hz, J=10.6 Hz), 3.41 (s, 3H),
3.39 (dd, 1H, J=2.4 Hz, J=9.7 Hz), 3.23 (dd, 1H, J=1.4 Hz, J=7.2 Hz),
3.18 (dd, 1H, J=8.2 Hz, J=9.2 Hz), 2.25–2.86 (m, 11H), 2.18 (s, 3H),
2.11 (s, 3H), 2.10 (s, 3H), 2.10 (s, 3H), 2.08 (m, 1H), 2.03 (s, 3H), 2.00–
2.03 (m, 2H), 1.97 (s, 3H), 1.96 (q, 1H, J=7.7 Hz), 1.93 (m, 1H), 1.70–
1.90 (m, 6H), 1.69 (s, 3H), 1.65 (m, 1H), 1.15–1.60 (m, 30H), 1.10 (s,
3H), 1.09 (d, 3H, J=6.8 Hz), 1.07 (t, 3H, J=7.7 Hz), 1.00 (t, 3H, J=
7.7 Hz), 0.98 (d, 3H, J=6.8 Hz), 0.81–0.94 ppm (m, 7H); 13C NMR
1122
www.chemasianj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2009, 4, 1114 – 1125

Efficient Synthesis of Deoxysugar Part of Versipelostatin
181.3, 171.8, 171.1, 170.7, 170.4, 170.1, 167.6, 147.2, 145.4, 140.4, 135.7,
135.5, 135.1, 129.3, 126.6, 124.1, 120.8, 116.2, 99.6, 99.3, 90.9, 88.0, 84.8,
80.0, 76.4, 75.3, 73.0, 72.6, 70.5, 69.0, 66.7, 66.0, 61.2, 57.5, 55.9, 51.6, 42.0,
39.6, 39.1, 36.9, 36.7, 36.2, 35.0, 34.7, 34.2, 33.9, 33.3, 32.9, 30.9, 30.6, 29.8,
29.7, 29.1, 26.8, 23.4, 22.8, 22.0, 21.6, 21.3, 21.2, 21.0, 20.0, 19.3, 19.0, 18.8,
18.3, 17.6, 16.4, 13.9, 11.5 ppm; IR (neat): n˜ =2933, 1789, 1740, 1681,
1591, 1524, 1457, 1368, 1347, 1243, 1100, 1065 cmꢀ1; HRMS (ESI-TOF)
calcd for C76H109NO23S [M+Na]+ m/z=1458.7009, found: 1458.6974.
3H, J=7.7 Hz), 1.07 (t, 3H, J=7.7 Hz), 1.00 (t, 3H, J=7.7 Hz), 0.98 (d,
3H, J=6.8 Hz), 0.91 (d, 3H, J=6.8 Hz), 0.87 (d, 3H, J=6.8 Hz),
0.86 ppm (m, 1H); 13C NMR (100 MHz, CDCl3): d=206.4, 198.3, 181.2,
171.9, 170.6, 170.4, 170.2, 167.6, 140.4, 135.6, 135.5, 135.2, 126.6, 120.7,
116.1, 99.9, 99.6, 98.7, 90.8, 87.9, 81.8, 80.0, 78.5, 73.0, 72.5, 70.8, 69.2,
68.0, 67.9, 67.8, 66.0, 57.5, 57.3, 42.0, 39.6, 39.1, 37.9, 36.9, 36.1, 36.0, 35.3,
34.6, 34.1, 33.7, 33.1, 32.9, 30.9, 30.6, 29.8, 29.7, 28.9, 27.9, 26.7, 23.4, 22.8,
22.7, 22.0, 21.6, 21.3, 21.2, 21.0, 20.9, 20.0, 19.3, 18.9, 18.6, 18.3, 17.9, 17.8,
16.4, 13.9, 11.5 ppm; IR (neat): n˜ =2970, 2936, 1788, 1743, 1680, 1588,
1455, 1371, 1241, 1154, 1092, 1065, 1011 cmꢀ1; HRMS (ESI-TOF) calcd
for C81H120O25 [M+Na]+ m/z=1515.8016, found: 1515.8007.
24: DBU (20.8 mL, 139 mmol) was added to a stirred solution of 23
(20.0 mg, 13.9 mmol) in CH3CN (500 mL) at 08C. After being stirred at
RT for 3 h, the reaction mixture was poured into saturated aq. NH4Cl.
The aqueous layer was extracted with two portions of ethyl acetate. The
combined extract was washed with 1m HCl, saturated aq. NaHCO3, and
brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue
was chromatographed on silica gel with hexane/ethyl acetate 40:60 to
give 24 (12.8 mg, 10.5 mmol, 75%). ½aꢁ2D1 =ꢀ15.88 (c=0.625, CHCl3);
1H NMR (400 MHz, CDCl3): d=5.42 (brs, 1H), 5.40 (s, 1H), 5.28 (m,
1H), 5.25 (m, 1H), 5.15 (d, 1H, J15,16 =9.7 Hz), 4.96 (brd, 1H, J=2.4 Hz),
4.77 (m, 1H), 4.68 (d, 1H, J1,2ax =9.2 Hz), 4.11 (dd, 1H, J16,37a =2.4 Hz,
26: NaOMe (20.0 mg) was added to a stirred solution of 25 (5.50 mg,
3.68 mmol) in methanol (500 mL) at RT. After being stirred under reflux
for 24 h, the reaction mixture was neutralized with Dowex 50WX4 and
filtered. The filtrate was poured into saturated aq. NH4Cl. The aqueous
layer was extracted with two portions of ethyl acetate. The combined ex-
tract was washed with brine, dried over MgSO4, filtered, and concentrat-
ed in vacuo. The residue was chromatographed on silica gel with CHCl3/
methanol 94:6 to give 26 (3.00 mg, 2.72 mmol, 75%). ½aꢁ2D4 =ꢀ38.98 (c=
0.305, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.82 (brs, 1H), 5.27 (s,
1H), 5.08 (d, 1H, J=10.1 Hz), 5.06 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.96
(d, 1H, J=3.4 Hz), 4.81 (dd, 1H, J=1.4 Hz, J=9.2 Hz), 4.11 (m, 1H),
4.08 (m, 1H), 3.92 (brs, 1H), 3.76–3.88 (m, 2H), 3.69 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.55–3.66 (m, 2H), 3.49 (ddd, 1H, J=4.8 Hz, J=11.6 Hz, J=
9.2 Hz), 3.42 (m, 1H), 3.40 (s, 3H), 3.31 (dd, 1H, J=9.2 Hz, J=9.2 Hz),
3.28 (dd, 1H, J=2.9 Hz, J=9.2 Hz), 3.22–3.27 (m, 2H), 2.87 (dd, 1H, J=
10.1 Hz, J=10.1 Hz), 2.84 (s, 1H), 2.54 (q, 1H, J=7.2 Hz), 2.39 (m, 1H),
2.25–2.35 (m, 2H), 2.23 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.00–2.17 (m,
7H), 1.95 (m, 1H), 1.86 (dd, 1H, J=8.2 Hz, J=14.0 Hz), 1.79 (m, 1H),
1.53–1.72 (m, 15H), 1.23–1.31 (m, 8H), 1.21 (d, 3H, J=6.3 Hz), 1.11 (m,
1H), 1.05 (d, 3H, J=7.2 Hz), 1.02 (s, 3H), 0.88–0.97 (m, 12H), 0.84 (d,
3H, J=7.2 Hz), 0.66 ppm (m, 1H,); 13C NMR (100 MHz, CDCl3): d=
205.4, 203.0, 166.5, 140.1, 135.3, 135.2, 133.1, 127.5, 121.4, 103.1, 100.6,
99.2, 98.5, 91.4, 87.3, 81.3, 80.7, 78.3, 73.2, 70.7, 70.5, 69.3, 68.4, 68.3, 67.8,
65.0, 61.1, 57.5, 57.4, 48.8, 43.6, 42.0, 41.8, 38.2, 38.0, 37.4, 36.7, 35.7, 35.2,
35.1, 34.9, 33.2, 32.3, 32.0, 31.1, 29.8, 29.0, 23.7, 23.2, 23.1, 22.0, 21.5, 20.5,
20.4, 19.3, 18.1, 17.8, 17.3, 14.8, 12.7 ppm; IR (solid): n˜ =3439, 2961, 2926,
1742, 1624, 1462, 1380, 1059, 1015, 989 cmꢀ1; HRMS (ESI-TOF) calcd for
C61H96O17 [M+Na]+ m/z=1123.6545, found: 1123.6553.
J
gem =11.1 Hz), 3.81 (dq, 1H, J4,5 =9.2 Hz, J5,6 =6.3 Hz), 3.67–3.74 (m,
2H), 3.63 (dq, 1H, J4,5 =9.2 Hz, J5,6 =6.3 Hz), 3.39 (s, 3H, Me), 3.39 (m,
1H), 3.29 (dd, 1H, J3,4 =2.4 Hz, J4,5 =9.2 Hz), 3.20 (brd, 1H, J=6.8 Hz),
3.12 (dd, 1H, J3,4 =J4,5 =9.2 Hz), 2.59 (m, 1H), 2.54 (m, 1H), 2.47 (m,
1H), 2.28–2.42 (m, 5H), 2.25 (dd, 1H, J2eq,2ax =13.0 Hz, J2eq,3 =4.8 Hz),
2.17 (m, 1H), 2.11 (s, 3H, Ac), 2.11 (s, 3H, Ac), 2.03 (s, 3H, Ac), 1.97 (s,
3H, Ac), 1.97 (q, 1H, J35,36 =7.2 Hz), 1.91 (m, 1H), 1.86 (q, 1H, J35,36
=
7.2 Hz), 1.82 (q, 1H, J31,32 =7.2 Hz), 1.74–1.81 (m, 3H), 1.72 (m, 1H),
1.69 (s, 3H), 1.59 (s, 3H), 1.22–1.59 (m, 24H), 1.10 (s, 3H), 1.09 (d, 3H,
J
18,38 =6.8 Hz), 1.07 (t, 3H, J31,32 =7.2 Hz), 1.01 (t, 3H, J35,36 =7.2 Hz), 0.98
(d, 3H, J27,42 =6.8 Hz), 0.91 (d, 3H, J6,33 =6.3 Hz), 0.88 (d, 3H, J20,39
=
6.8 Hz), 0.85 ppm (m, H-17b); 13C NMR (67.8 MHz, CDCl3): d=198.2,
181.2, 171.8, 171.1, 170.6, 170.4, 170.3, 167.6, 140.3, 135.6, 135.5, 135.1,
126.6, 120.7, 116.1, 100.1, 99.6, 90.7, 87.9, 79.7, 78.0, 76.0, 73.0, 72.5, 70.8,
69.2, 68.5, 68.2, 65.9, 61.3, 57.5, 56.5, 41.9, 39.5, 39.1, 36.8, 36.1, 34.3, 34.1,
33.7, 33.1, 32.9, 31.6, 30.9, 30.6, 29.7, 28.8, 26.7, 23.4, 22.8, 22.7, 22.0, 21.6,
21.3, 21.2, 21.1, 21.0, 20.0, 19.3, 18.8, 18.5, 18.2, 17.7, 16.3, 13.8, 11.5 ppm;
IR (neat): n˜ =3464, 2936, 1788, 1741, 1680, 1590, 1455, 1373, 1239, 1065,
1021 cmꢀ1
1245.6913, found: 1245.6958.
25: mixture of 24 (12.8 mg, 10.5 mmol, 1.00 equiv),
;
HRMS (ESI-TOF) calcd for C68H102O19 [M+Na]+ m/z=
A
4 (13.6 mg,
28: According to the method for the synthesis of 17, 27 (0.548 g,
1.80 mmol), 22 (1.41 g, 2.71 mmol) and MS-4ꢁ (2.71 g) in CH2Cl2
(18.0 mL) were treated with a mixture of 1.00m IBr in CH2Cl2 (3.60 mL,
3.60 mmol) and TBAB (1.45 g, 4.50 mmol) at 08C for 2 h. N,N-Diisopro-
pylethylamine (0.156 mL, 0.900 mmol) was then added to the reaction
mixture. Stirring for 20 h at the same temperature gave 28 (1.15 g,
1.74 mmol, 94%, b/a=94:6) after purification. The a,b isomers were sep-
arated by chromatography on silica gel with toluene/ethyl acetate 92:8.
½aꢁ2D8 =ꢀ13.88 (c=0.910, CHCl3); 1H NMR (400 MHz, CDCl3): d=8.19
(d, 2H, J=8.7 Hz), 7.39 (d, 2H, J=8.7 Hz), 5.28 (ddd, 1H, J=3.4 Hz, J=
3.4 Hz, J=3.4 Hz), 5.01 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.96 (d, 1H, J=
3.9 Hz), 4.18 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 3.87 (dq, 1H, J=6.3 Hz, J=
9.2 Hz), 3.85 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.62 (ddd, 1H, J=5.3 Hz,
J=9.2 Hz, J=11.1 Hz), 3.47–3.43 (m, 2H), 3.35 (dd, 1H, J=3.4 Hz, J=
9.2 Hz), 3.22–3.32 (m, 5H), 2.36 (dd, 1H, J=5.3 Hz, J=13.0 Hz), 2.12 (s,
3H), 2.09 (ddd, 1H, J=1.9 Hz, J=3.4 Hz, J=14.5 Hz), 1.75 (ddd, 1H,
J=3.4 Hz, J=9.2 Hz, J=14.5 Hz), 1.56 (ddd, 1H, J=3.4 Hz, J=11.1 Hz,
J=13.0 Hz), 1.31 (d, 3H, J=6.3 Hz), 1.25 (d, 3H, J=6.3 Hz), 0.89 (s,
9H), 0.11 (s, 3H), 0.10 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=
170.1, 147.2, 145.4, 129.3, 124.1, 99.0, 92.8, 84.8, 79.5, 75.3, 70.2, 69.3, 66.7,
55.9, 51.6, 38.4, 35.0, 29.6, 25.8, 21.2, 18.4, 18.1, 17.6, ꢀ4.1, ꢀ5.1 ppm; IR
(solid): n˜ =2933, 2859, 1736, 1607, 1523, 1451, 1316, 1243, 1173, 1065,
1002 cmꢀ1; HRMS (ESI-TOF) calcd for C29H47NO12SSi [M+Na]+ m/z=
684.2486, found: 684.2490.
31.4 mmol) and pulverized activated MS-4ꢁ (30.0 mg) in dry toluene
(0.300 mL) was stirred at RT for 30 min under argon to remove a trace
amount of water. The reaction mixture was then cooled to ꢀ948C
(hexane–liquid N2 bath). After 5 min, a solution of iodine (9.29 mg,
36.6 mmol) in toluene (50.0 mL) and triisopropylsilane (0.430 mL,
2.09 mmol) was added to the reaction mixture. After being stirred for
1.5 h, the reaction mixture was neutralized with triethylamine at ꢀ948C
and filtered through Celite. Immediately the filtrate was poured into a
mixture of saturated aq. NaHCO3 and saturated aq. Na2S2O3, with cool-
ing. The aqueous layer was extracted with two portions of ethyl acetate.
The combined extract was washed with brine, dried over MgSO4, filtered,
and concentrated in vacuo. The residue was chromatographed on silica
gel with hexane/ethyl acetate 50:50 and further purified by gel permea-
tion chromatography (GPC) to give 25 (12.7 mg, 8.50 mmol, 81%, b/a=
94:6). The b/a ratio was determined by 1H NMR analysis (400 MHz).
½aꢁ2D5 =ꢀ4.218 (c=0.700, CHCl3); 1H NMR (400 MHz, CDCl3): d=5.42
(brs, 1H), 5.39 (s, 1H), 5.39 (m, 1H), 5.22–5.26 (m, 2H), 5.15 (d, 1H, J=
9.7 Hz), 5.05 (dd, 1H, J=1.4 Hz, J=9.7 Hz), 4.92 (brd, 1H, J=2.9 Hz),
4.76 (m, 1H), 4.66 (brd, 1H, J=8.7 Hz), 4.54 (dd, 1H, J=2.9 Hz, J=
9.7 Hz), 4.10 (dd, 1H, J=2.9 Hz, J=11.1 Hz), 3.89 (dq, 1H, J=6.3 Hz,
J=9.7 Hz), 3.80 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.71 (m, 1H), 3.71 (m,
1H), 3.56 (dq, 1H, J=6.3 Hz, J=9.7 Hz), 3.44 (ddd, 1H, J=4.8 Hz, J=
9.7 Hz, J=11.6 Hz), 3.36 (s, 3H), 3.26 (dd, 1H, J=2.9 Hz, J=9.7 Hz),
3.23 (dd, 1H, J=9.7 Hz, J=9.7 Hz), 3.20 (m, 1H), 2.40–2.84 (m, 8H),
2.28–2.39 (m, 3H), 2.22 (dd, 1H, J=4.8 Hz, J=13.0 Hz), 2.19 (m, 1H),
2.18 (s, 3H), 2.10 (s, 3H), 2.09 (s, 3H), 2.05 (m, 1H), 2.03 (s, 3H), 1.97 (s,
3H), 1.95 (q, 1H, J=7.7 Hz), 1.90 (m, 1H), 1.88 (q, 1H, J=7.7 Hz), 1.83
(q, 1H, J=7.7 Hz), 1.70–1.82 (m, 4H), 1.69 (s, 3H), 1.65 (s, 1H), 1.58 (s,
3H), 1.20–1.58 (m, 24H), 1.17 (d, 3H, J=6.3 Hz), 1.10 (s, 3H), 1.07 (d,
29: DBU was added to a stirred solution of 28 (1.12 g, 1.69 mmol) in
CH3CN (8.45 mL) (252 mL, 1.69 mmol) at 08C. After being stirred at RT
for 6 h, the reaction mixture was poured into saturated aq. NH4Cl. The
aqueous layer was extracted with two portions of ethyl acetate. The com-
bined extract was washed with 1m HCl, saturated aq. NaHCO3, and
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1123

H. Tanaka, T. Takahashi et al.
FULL PAPERS
brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue
was chromatographed on silica gel with hexane/ethyl aetate 60:40 to give
29 (0.580 mg, 1.29 mmol, 77%). ½aꢁ2D9 =ꢀ14.88 (c=0.930, CHCl3);
1H NMR (400 MHz, CDCl3): d=5.28 (ddd, 1H, J=3.4 Hz, J=3.4 Hz, J=
3.4 Hz), 5.01 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.95 (d, 1H, J=3.9 Hz),
3.88 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.65 (dq, 1H, J=6.3 Hz, J=9.2 Hz),
3.31–3.42 (m, 5H), 3.33 (ddd, 1H, J=2.4 Hz, J=9.2 Hz, J=9.2 Hz), 2.37
(d, 1H, J=2.4 Hz), 2.25 (dd, 1H, J=5.3 Hz, J=13.0 Hz), 2.12 (s, 3H),
2.10 (ddd, 1H, J=1.9 Hz, J=3.4 Hz, J=14.5 Hz), 1.75 (ddd, 1H, J=
3.4 Hz, J=9.2 Hz, J=14.5 Hz), 1.50 (ddd, 1H, J=3.9 Hz, J=11.1 Hz, J=
13.0 Hz), 1.26 (d, 3H, J=6.3 Hz), 1.24 (d, 3H, J=6.3 Hz), 0.89 (s, 9H),
0.11 (s, 3H), 0.09 ppm (s, 3H); 13C NMR (100 MHz, CDCl3): d=170.2,
99.9, 92.9, 79.3, 78.1, 76.1, 70.5, 69.5, 68.6, 56.5, 38.5, 34.3, 25.8, 21.2, 18.4,
18.2, 17.7, ꢀ4.1, ꢀ5.0 ppm; IR (neat): n˜ =3469, 2933, 2859, 1744, 1370,
1242, 1089, 987 cmꢀ1; HRMS (ESI-TOF) calcd for C21H40O8Si [M+Na]+
m/z=471.2390, found: 471.2396.
(400 MHz). 1H NMR (400 MHz, CD2Cl2): d=8.54 (s, 1H), 6.10 (dd, 1H,
J=2.9 Hz, J=7.7 Hz), 5.30–5.35 (m, 2H), 5.05 (dd, 1H, J=1.9 Hz, J=
9.7 Hz), 4.91 (d, 1H, J=3.9 Hz), 4.47 (dd, 1H, J=3.4 Hz, J=9.7 Hz),
4.06 (dq, 1H, J=6.8 Hz, J=6.8 Hz), 3.87 (dq, 1H, J=6.3 Hz, J=9.7 Hz),
3.60 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.51 (dd, 1H, J=2.9 Hz, J=6.8 Hz),
3.43 (ddd, 1H, J=5.3 Hz, J=9.2 Hz, J=11.6 Hz), 3.32 (s, 3H), 3.21 (dd,
1H, J=9.2 Hz, J=9.2 Hz), 2.27–2.76 (m, 5H), 2.21 (dd, J=5.3 Hz, J=
13.0 Hz), 2.10 (s, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 1.92–2.05 (m, 2H), 1.73
(ddd, 1H, J=2.9 Hz, J=9.7 Hz, J=14.0 Hz), 1.48 (ddd, 1H, J=3.9 Hz,
J=11.6 Hz, J=13.0 Hz,), 1.30 (d, 3H, J=6.3 Hz), 1.17 (d, 3H, J=
6.3 Hz), 1.13 ppm (d, 3H, J=6.3 Hz); IR (solid): n˜ =3315, 2979, 2940,
1743, 1721, 1674, 1370, 1245, 1157 cmꢀ1
26: According to the method for the synthesis of 15,
13.2 mmol), (20.2 mg, 26.4 mmol), and pulverized activated MS-4ꢁ
.
3
(12.0 mg,
6
(26.0 mg) in toluene (390 mL) were treated with a solution of iodine
(8.32 mg, 33.0 mmol) in toluene (30.0 mL) and triethylsilane (0.421 mL,
2.64 mmol) at ꢀ948C for 1.5 h, to provide 26 (7.90 mg, 5.23 mmol, 40%, b/
a=95:5).
30: According to the method for the synthesis of 15, 29 (0.515 mg,
1.15 mmol), 4 (496 mg, 1.72 mmol), and pulverized activated MS-4ꢁ
(1.72 g) in toluene (23.0 mL) were treated with a solution of iodine
(582 mg, 2.30 mmol) in toluene (0.230 mL) and triisopropylsilane
(23.5 mL, 0.115 mmol) at ꢀ948C for 1.5 h to provide 30 (705 mg,
0.981 mmol, 85%, b/a=95:5) after purification. ½aꢁ2D1 =ꢀ14.78 (c=1.02,
CHCl3); 1H NMR (400 MHz, CDCl3): d=5.39 (ddd, 1H, J=3.4 Hz, J=
3.4 Hz, J=3.4 Hz), 5.25 (ddd, 1H, J=3.4 Hz, J=3.4 Hz, J=3.4 Hz), 5.04
(dd, 1H, J=1.4 Hz, J=9.2 Hz), 4.99 (dd, 1H, J=1.9 Hz, J=9.2 Hz), 4.91
(d, 1H, J=3.4 Hz), 4.54 (dd, 1H, J=3.4 Hz, J=9.2 Hz), 3.83–3.92 (m,
2H), 3.57 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.43 (ddd, 1H, J=4.8 Hz, J=
9.2 Hz, J=11.6 Hz), 3.36 (s, 3H), 3.30 (dd, 1H, J=3.4 Hz, J=9.2 Hz),
3.23 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 2.38–2.84 (m, 4H), 2.22 (dd, 1H, J=
4.8 Hz, J=13.0 Hz), 2.17 (s, 3H), 2.10 (s, 3H), 2.10 (m, 1H), 2.09 (s, 3H),
2.08 (m, 1H), 1.68–1.82 (m, 2H), 1.50 (ddd, 1H, J=3.4 Hz, J=11.6 Hz,
J=13.0 Hz), 1.25 (d, 3H, J=6.3 Hz), 1.21 (d, 3H, J=6.3 Hz), 1.16 (d,
3H, J=6.3 Hz), 0.88 (s, 9H), 0.10 (s, 3H), 0.09 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3): d=206.4, 171.9, 170.2, 99.7, 98.7, 92.9, 81.8, 79.5, 78.6,
70.5, 69.5, 68.0, 67.9, 67.8, 57.3, 38.3, 38.0, 36.2, 35.4, 29.9, 27.9, 25.9, 21.2,
21.1, 18.4, 18.2, 17.9, 17.8, ꢀ4.1, ꢀ5.0 ppm; IR (neat): n˜ =2934, 2858,
1745, 1723, 1370, 1243, 1154, 1067, 1012 cmꢀ1; HRMS (ESI-TOF) calcd
for C34H58O14Si [M+Na]+ m/z=741.3494, found: 741.3491.
Acknowledgements
This work was financially supported by NEDO (New Energy and Indus-
trial Technology Development Organization) and was partially supported
by JSPS reserch fellowships for young scientists (DC2).
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31: Hydrogen fluoride pyridine (1.41 mL) was added to a stirred solution
of 30 (0.510 g, 0.709 mmol) in pyridine (5.65 mL) at 08C. After being
stirred at RT for 5 h, the reaction mixture was poured into saturated aq.
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filtered, and concentrated in vacuo. The residue was chromatographed
on silica gel with hexane/ethyl acetate 35:65 to give 31 (343 mg,
0.567 mmol, 80%, a/b=29:71). 1H NMR (400 MHz, CDCl3): d=5.38–
5.40 (m, 2H), 5.29 (ddd, 1H, J=3.4 Hz, J=3.4 Hz, J=3.4 Hz), 5.27 (ddd,
1H, J=3.4 Hz, J=3.4 Hz, J=3.4 Hz), 5.15 (m, 1H), 5.03–5.08 (m, 3H),
4.96 (d, 1H, J=3.4 Hz), 4.93 (d, 1H, J=3.4 Hz), 4.54 (dd, 1H, J=3.4 Hz,
J=9.2 Hz), 4.54 (dd, 1H, J=3.4 Hz, J=9.2 Hz), 4.26 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.95 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.91 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.91 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.64 (dq, 1H, J=6.3 Hz,
J=9.2 Hz), 3.57 (dq, 1H, J=6.3 Hz, J=9.2 Hz), 3.44 (ddd, 1H, J=
4.8 Hz, J=9.2 Hz, J=11.6 Hz), 3.44 (ddd, 1H, J=4.8 Hz, J=9.2 Hz, J=
11.6 Hz), 3.38 (s, 3H), 3.37 (s, 3H), 3.28–3.35 (m, 3H), 3.25 (dd, 1H, J=
9.2 Hz, J=9.2 Hz), 3.24 (dd, 1H, J=9.2 Hz, J=9.2 Hz), 3.01 (d, 1H, J=
5.8 Hz), 2.40–2.85 (m, 8H), 2.04–2.27 (m, 24H), 1.96 (ddd, 1H, J=
3.4 Hz, J=3.4 Hz, J=15.0 Hz), 1.76–1.83 (m, 2H), 1.69 (ddd, 1H, J=
3.4 Hz, J=9.7 Hz, J=14.0 Hz), 1.49–1.58 (m, 2H), 1.21–1.31 (m, 12H),
1.17 (d, 3H, J=6.3 Hz), 1.17 ppm (d, 3H, J=6.3 Hz); IR (neat): n˜ =3450,
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.
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1124
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Chem. Asian J. 2009, 4, 1114 – 1125

Efficient Synthesis of Deoxysugar Part of Versipelostatin
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Received: November 27, 2008
Published online: April 3, 2009
Chem. Asian J. 2009, 4, 1114 – 1125
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1125