Highly Diastereoselective Route to α-Glucosidase Inhibitors, Neosalacinol and Neoponkoranol

Article abstract of DOI:10.1021/acs.joc.5b02894

A facile and highly diastereoselective route to potent natural α-glucosidase inhibitors, i.e., neosalacinol (4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine "Salacia" was developed by intramolecular cyclization of appropriately substituted sulfides (9 and 12).

Full text of DOI:10.1021/acs.joc.5b02894

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Note
Highly Diastereoselective Route to alpha-Glucosidase
Inhibitors, Neosalacinol and Neoponkoranol
Genzoh Tanabe, Youya Matsuda, Misato Oka, Yousuke Kunikata, Nozomi Tsutsui, Weija
Xie, Gorre Balakishan, Mumen F. A. Amer, Shinsuke Marumoto, and Osamu Muraoka
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02894 • Publication Date (Web): 25 Mar 2016
Downloaded from http://pubs.acs.org on April 7, 2016
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Highly Diastereoselective Route to -Glucosidase Inhibitors, Neosalacinol and Neoponko-
ranol
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†
†
†
†
†
‡
Genzoh Tanabe, Youya Matsuda, Misato Oka, Yousuke Kunikata, Nozomi Tsutsui, Weija Xie,
§
¶
II
,†
Gorre Balakishan, Mumen F. A. Amer, Shinsuke Marumoto, and Osamu Muraoka*
†
‡
II
Faculty of Pharmacy, Joint Research Center, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharma-
ceutical University, Nanjing 210009, P. R. China
§
Department of Organic Chemistry, Telangana University, Nizamabad 503322, Telangana State, India
¶
Faculty of Pharmacy, Applied Science Private University, Al Arab St 21, Amman 11931, Jordan.
Table of Contents
OH
R
1) intramolecular
MsO
BnO
cyclization
OH
n
S
X-
S+ OH
TBDPSO
2) deprotection
OBn
HO
OBn
OBn
OBn
HO
OH
OBn
O
9
:
R =
OBn 12 : R =
neosalacinol (4) : n = 1
neoponkoranol (6) : n = 3
OBn
OBn
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Abstract
A facile and highly diastereoselective route to potent natural -glucosidase inhibitors, i.e., neosalacinol
4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine “Salacia” was developed
0
1
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0
(
by intramolecular cyclization of appropriately substituted sulfides (9 and 12).
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In the late 1990s, Muraoka et al. isolated a highly potent -glucosidase inhibitor called salacinol (1)
from Salacia reticulata roots and stems, which have traditionally been used in Ayurveda for the treat-
ment of diabetes. The -glucosidase inhibitory activity of 1 was revealed to be as potent as that of
8
9
1
1
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0
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0
1
voglibose and acarbose, which are used clinically worldwide. The structure of 1 revealed by X-ray
analysis is unique; the sulfonium cation and sulfonate anion yield an inner salt to compose a spirobicy-
1
clic structure as shown in Figure 1. After the isolation of 1, the related sulfonium sulfonates, i.e., ko-
2
3
4
5
talanol (2) and ponkoranol (3), and their desulfonated analogs, i.e., neosalacinol (4) neokotalanol (5),
6
and neoponkoranol (6), were subsequently isolated from plants of the same genus and identified as
compounds responsible for the antidiabetic activity, composing a new class of -glucosidase inhibitors.
Human clinical trials with the extract of Salacia reticulata on patients with type-2 diabetes have shown
7
its effective treatment with minimal side effects. These inhibitors (1–6) have attracted much attention
owing to their high inhibitory activity and intriguing structure, and intensive structure–activity relation-
8
9
ship (SAR) studies, including their total syntheses, have been conducted. In 2010, the crystal structure
of a complex of salacinol (1) with the human N-terminal catalytic domain of maltase-glucoamylase was
8
d
revealed by Pinto and co-workers, and thereafter, several inhibitors with measurably better activities
8
c
have been developed with the aid of in silico drug design.
HO
4'
OH OH OH
OH OH OH
S+ OR OH
OH OH
3
'
O
O
HO
3
'
4'
2
'
S
1'
2'
O
S+ OR OH OH
-O
1
'
S+ OH
S+
HO
HO
HO
HO
HO
kotalanol (2) : R = SO
neokotalanol (5) : R = H
OH
HO
OH
HO
OH
HO
OH
-
-
3
ponkoranol (3) : R = SO
neoponkoranol (6) : R = H
3
salacinol (1)
neosalacinol (4)
Figure. 1 A new class of natural -glucosidase inhibitors
These SAR studies employed a common approach to construct the sulfonium structure: the inter-
molecular S-alkylation of thiosugar (8) with cyclic sulfates (A) for sulfonates (1, 2, 3) or with epoxides
(
B) for their desulfonates (4, 5, 6), respectively, as shown in Scheme 1.
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Scheme 1. Conventional Routes to Sulfonium Salts
OR2 OR2
OR2 OR2
O
O
S
O
S+
OSO -
3
O
A
0
1
2
3
4
5
6
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9
0
1
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0
1
2
3
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5
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8
9
0
1
R O
1, 2 or 3
1
OR1
R O
S
1
R O
1
OR1
R O
OR2
O
OH OR2
8
R1 = H, Bn or PMB
OR2
S+ OR2
B
1
4, 5 or 6
R O
1
OR1
R O
Although these routes are general and applicable to the syntheses of a wide range of sulfoniums re-
quired for the SAR study, they suffer from disadvantages in some instances as follows: 1) S-alkylation
with cyclic sulfates (A) often requires a long reaction period (~7 days or more) with low yield; 2) a co-
existing acid HA as the catalyst in the process B causes partial decomposition of reactants epoxides or
8,9
products; and 3) poor diastereoselectivity in both processes. Thus, an alternative route leading to
compounds that are inefficiently synthesized via the above route is required. In this paper we have de-
veloped a facile and efficient alternative route to neosalacinol (4) by employing an intramolecular S-
alkylation of an appropriate disulfide. The reaction proceeded with high diastereoselectivity to give the
target sulfonium (4) in good overall yield. Application of the protocol to another neo-type inhibitor
called neoponkoranol (6) successfully gave the desired inhibitor also in good yield.
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Scheme 2. Retrosynthesis of 4 and 6 via Intramolecular Cyclization
O
OBn
OBn
OBn
OH
OH OH
OBn
OBn
O
OBn
OBn
OBn
O
OBn
TsO
BnO
MsO-
OH
MsO
OBn
+
HS
OH
0
1
2
3
4
5
6
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8
9
0
1
2
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5
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9
0
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9
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
6
7
8
9
0
S+ OH
S
OBn
MsO
-
11
S+ OH OH
HO
MsO
TBDPSO
TBDPSO
BnO
S
OBn
+
HO
1
3
OBn
BnO
O
HO
OH
HO
OH
9
neosalacinol (4)
BnO
OBn
O
neoponkoranol (6)
10
12
10
O
Synthesis of neosalacinol (4). The retrosynthetic routes to neosalacinol (4) and neoponkoranol (6)
via intramolecular S-alkylation are provided in Scheme 2. The reactant (9) for the synthesis of 4 was
8f
prepared as follows. According to the literature, D-xylose was first converted to tosylate (14), which
was treated with BnBr in the presence of NaH to give the corresponding benzyl ether (15) in 95% yield.
After the replacement of the TsO moiety of 15 by AcSK, the resultant thioester (16) was reduced with
4
LiAlH to give the thiol (10) in good yield. The thiol (10) was then subjected to a coupling reaction
1
0
with epoxide (11), giving the corresponding sulfide (17) in 90% yield. Acidic hydrolysis of the acetal
moiety of 17 followed by the NaBH reduction of the hemiacetal (18) gave a tetraol (19) in 52% yield
4
from 17. Selective protection of the 1,2-glycol moiety of the tetraol (19) with 2,2-DMP gave 20 in 62%
yield. Protection of the remaining two secondary hydroxyls in 20 with BnBr led to the corresponding
benzyl ether (21). Then, the 1,3-dioxolane moiety of 21 was removed by acid hydrolysis to give 1,2-
glycol (22). Selective protection of the primary hydroxyl of 22 with TBDPSCl followed by the
mesylation of the resultant alcohol (23) furnished 9 in good yield. Gradual transformation of 9 into
sulfonium salt (24) was observed, therefore 9 was subjected to the next reaction immediately after
purification. Finally heating the sulfide (9) in EtOH under reflux for 3 h gave the desired sulfonium salt
(
24) in 90% yield with excellent diastereo ratio (/ = ~23/1). The ratio was determined on the basis of
1
H-NMR specroscopic measurement with respect to the integration of the tert-butyl moiety of the
TBDPS group of the products (-24:  1.00, -24:  0.97). The major isomer -24 was successfully
H
H
separated from the -isomer -24 by silica gel column chromatography. The positive FAB-MS
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spectrum run in the negative mode showed peaks at m/z 943 corresponding to the sulfonium cation
+
structure [M–CH
3
SO
3
] . The relative stereochemistry of the side chain of -24 was confirmed to be in
anti-relationship to the TBDPSOCH
2
moiety at C-4 by nuclear Overhauser effect spectroscopy. Finally,
0
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9
0
the simultaneous deprotection of Bn and TBDPS moieties of -24 under acidic hydrogenolysis
conditions successfully gave the target neosalacinol (4, X = CH
3
SO
3
) in 90% yield. By the ion-
–
exchange reaction of 4 (X = CH
3
SO
3
) with IRA-400J (Cl form), 4 (X = CH
3
SO ) was converted to the
3
8
e,9h
known sulfonium salt
(4, X = Cl) (Scheme 3), the physical and spectroscopic properties of which
8e,9h
were consistent with those of an authentic specimen obtained via an alternative route
(Scheme 3) .
Scheme 3. Synthesis of Neosalacinol (4)
O
OH
OBn
OH
RS
OBn
OBn
TsO
RO
11
OBn
BnO
O
S
OBn
1
0%H
2
SO
4
S
OBn
KSAc, DMF
0 °C, 2 h
NaOH, EtOH
reflux, 1.5 h
BnO
O
dioxane, reflux, 1.5 h
BnO
HO
8
D
-xylose
O
O
O
O
9
3%
90%
O
O
O
17
18
O
OH
BnBr, NaH, DMF
14 : R = H
15 : R = Bn 0 °C, 30 min
LiAlH , THF
16 : R = Ac
10 : R = H
9
5%
4
96%
OH
0
°C, 1 h
OH
OBn
OR
OBn
OBn
OBn
NaBH4, MeOH
S
OBn
OBn
HO
2,2-DMP, PTSA, acetone
0 °C-rt, 3 h
10% HCl, MeOH
60 °C, 1 h
RO
HO
S
0
°C, 1 h
BnO
S
OBn
O
O
OBn
S
OBn
HO
5
2% from 17
OH
62%
HO
BnO
OH
BnO
OBn
BnO
OR
OH
19
BnBr, NaH, DMF
0 °C, 1 h
20 : R = H
21 : R = Bn
TBDPSCl, imidazole, DMF
22 : R = H
23 : R = TBDPS
93%
50 °C, 2 h 96% from 21
OBn
OH
OBn
MsCl, NEt
3
, NMe
3
HCl (cat.)
TBDPSO
OBn
H , Pd-C, 20% aq. TFA,
AcOEt, rt, 24 h
X-
OH
NOE
H C
OBn
2
2
S+ OH
CH Cl 0°C, 2 h
2
2
,
MsO
BnO
EtOH, reflux, 3 h
90%
S
OBn
H
S+
OBn
HO
9
5%
MsO-
90%
TBDPSO
(
dr, /= ~ 23/1)
HO
OH
OBn
BnO
OBn
9
neosalacinol (4)

-24
-
IRA400J (Cl form)
X = CH
X = Cl
3 3
SO
2
MeOH, H O, rt, 12 h 89%
Synthesis of neoponkoranol (6). The protocol was then applied to the synthesis of
neoponkoranol (6) (Scheme 4). The sulfide (12) for cyclization was synthesized as follows. Tosylate
11
(
25), prepared starting from D-glucose according to the literature, was coupled with 10 in the
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presence of NaOH to give the corresponding sulfide (26) in 97% yield. The acetal moiety of the sulfide
26) was selectively hydrolyzed with TFA, and the resultant hemiacetal was subsequently reduced with
NaBH to give the triol (27) in 87% overall yield from the sulfide (26). Selective protection of the 1,2-
glycol moiety of 27 with 2,2-DMP followed by the protection of the remaining secondary hydroxyl in
8 with BnBr led to 29 in good yield. After the 1,3-dioxolane moiety of 29 was selectively hydrolyzed
by TFA, the resultant 1,2-glycol (30) was treated with TBDPSCl to give the corresponding silyl ether
(
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
(
31) in 87% yield. Finally, the mesylation of 31 furnished the key sulfide (12) in 92% yield.
Compound 12 was then heated in EtOH under reflux. The reaction proceeded with high
diastereoselectivity to give -32 in good yield (94%, dr, / = ~20/1). After the benzyl moieties of -
32 were removed by hydrogenolysis on Pd–C at 60 °C in a mixture of aqueous TFA and 1,4-dioxane,
–
–
–
MsO of the resultant sulfonium salt (33) was exchanged with Cl by IRA-400J (Cl form) to give an
~
1:1 mixture of hemiacetal (34), which was finally reduced with NaBH to give neoponkoranol (6) in
4
52% yield. Physical and spectroscopic properties of the product (6) were consistent with those of an
6
authentic specimen obtained via an alternative route (Scheme 4).
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Scheme 4. Synthesis of Neoponkoranol (6)
OBn
OBn
OBn
OBn
OBn
OBn
OBn
OBn
OBn
O
OBn
OBn
10
O
O
O
1
) aq. TFA, THF
90°C, 4 h
O
OBn
OBn
NaOH, EtOH, reflux, 3 h
TsO
BnO
D-glucose
S
HO
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
S
OBn
S
97%
2) NaBH
4
, THF-H
2
O
BnO
HO
BnO
O
HO
0°C, 4 h
OBn
87%
OH
OH
BnO
OH
26
2
5
27
O
OBn
OBn
OBn
OBn
OBn
OBn
OBn
O
OBn
OBn
O
OBn
OBn
O
2
0
,2-DMP, PTSA, acetone
°C-rt, 1 h
3 3
MsCl, NEt , NMe ·HCl (cat.)
O
O
aq. TFA, CHCl
89%
, rt, 4 h
CH
2
Cl
2
, 0 °C, 30 min
S
OBn
3
RO HO
BnO
S
MsO
TBDPSO
S
8
5%
92%
BnO
OR
OBn
30 : R = H
BnO
OBn
12
2
8 : R = H
BnBr, NaH, DMF, 0 °C, 2 h
7%
TBDPSCl, imidazole, DMF, rt, 3 h
8%
29 : R = Bn
31 : R = TBDPS
8
9
OBn
OH
OH
OBn
OBn
OH
OH
O
H , Pd-C, 20% aq. TFA
dioxane, 55-60 °C, 18 h
O
2
EtOH, reflux, 5 h
NOE
NaBH
4 2
, H O, 0 °C, 2 h
2
H C
X-
S+
OBn
MsO-
S+
Neoponkoranol (6)
H
9
4%
52% from -32
TBDPSO
HO
(
dr, /= ~ 20/1)
BnO
OBn
-32
HO
OH

-
IRA400J (Cl form)
33 : X = MsO
34 : X = Cl
2
MeOH, H O, rt, 12 h
In summary, a new and highly diastereoselective route to neosalacinol (4), a potent -glucosidase
inhibitor isolated from the traditional Ayurvedic medicine “Salacia” has been developed. The process
was successfully applied to the synthesis of neoponkoranol (6) and would be applicable to other “neo-
types” of these characteristic cyclic sulfoniums. The present protocol consists of generally-used practi-
cal transformations, avoiding disadvantages, i.e. poor diastereoselectivity or long reaction period, en-
countered in some instances via the conventional methods, and provides an efficient alternative route
for SAR studies on this class of -glucosidase inhibitors.
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EXPERIMENTAL SECTION
General Experimental Details. Mps were determined on a hot-stage melting point apparatus
0
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and are uncorrected. IR spectra were measured on a FT-IR spectrophotometer. NMR spectra were rec-
1
13
orded on a FT-NMR spectrometer ( H, 500 or 800 MHz; C, 125 or 200 MHz). Chemical shifts ()
and coupling constants (J) are given in ppm and Hz, respectively. DSS was used as an internal stand-
2
ard in the measurement of NMR spectra in D O. Low-resolution and high-resolution mass spectra
were recorded on a double-focusing mass spectrometer (FAB) or a orbitrap mass spectrometer (ESI).
Optical rotations were determined with a digital polarimeter. Column chromatography was performed
over silica gel (45–106 M). HPLC was performed on a DAISOPAK-SP120-5-ODS-BP (20x250 mm)
with a refractive index detector. All the organic extracts were dried over anhydrous Na
2 4
SO prior to
evaporation.
3-O-Benzyl-1,2-O-isopropylidene-5-O-tosyl-thio-α-D-xylofuranose (15). A solution of
8
f
1
,2-O-isopropylidene-5-O-tosyl-α-D-xylofuranose (14, 13.4 g, 39.0 mmol) in DMF (70 mL) was
added dropwise to a mixture of NaH (3.25 g, 81.3 mmol, 60% in liquid paraffin), BnBr (5.3 mL, 44.3
mmol), and DMF (100 mL) at 0°C. After being stirred at 0 °C for 1 h, the mixture was poured into
cold water (900 mL) and extracted with Et O (3×200 mL). The extract was washed with brine and
2
condensed to give a colorless oil (18.4 g), which on column chromatography (n-hexane-acetone, 10:1
→
5:1) gave title compound 15 (16.1 g, 95%) as a colorless oil. The spectral properties of 15 agreed
8f
well with those reported.
3-O-Benzyl-1,2-O-isopropylidene-5-thio-α-D-xylofuranose Acetate (16). A mixture of 15
(15.8 g, 36.4 mmol), KSAc, (6.23 mg, 54.6 mmol), and DMF (50 mL) was heated at 80 °C for 2 h. Af-
ter being cooled, the reaction mixture was diluted with cold water (300 mL) and extracted with EtOAc
(
2×100 mL, 1×50 mL). The extract was washed with brine and condensed to give a brown oil (13.2 g),
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which on column chromatography (n-hexane-EtOAc, 10:1 → 3:1) gave title compound 16 (11.4 g,
24
9
3%) as a pale yellow oil. []
D
–14.4 (c 1.10, CHCl
3
). IR (neat): 2986, 2936, 1693, 1454, 1373, 1354,
) : 1.30/1.47 [each 3H, s,
), 3.15 (1H, dd, J = 13.4, 6.9, H-5a), 3.28 (1H, dd, J = 13.4, 7.4, H-5b),
.91 (1H, d, J = 3.2, H-3), 4.27 (1H, ddd, J = 7.4, 6.9, 3.2, H-4), 4.52/4.68 (each 2H, d, J = 11.6,
-1
1
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
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7
8
9
0
1
2
3
4
5
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8
9
0
1256, 1215, 1165, 1134, 1076, 1026 cm . H NMR (500 MHz, CDCl
3
C(CH ], 2.33 (3H, s, COCH
3
)
2
3
3
1
3
CH
2
Ph), 4.61 (1H, d, J = 3.9, H-2), 5.91 (1H, d, J = 3.9, H-1), 7.29–7.38 (5H, m, arom.). C NMR
) : 26.2/26.8 [C(CH ], 27.1 (C-5), 30.4 (COCH ), 72.0 (CH Ph), 79.1 (C-4), 82.0
)], 127.7/128.0/128.4 (d, arom.), 137.2 (s, arom.), 195.2
(
(
125 MHz, CDCl
3
3
)
2
3
2
C-3), 82.1 (C-1), 105.1 (C-1), 111.7 [C(CH
3
+
+
+
(COCH
3
). LRMS (FAB) m/z: 339 [M+H] , 361 [M+Na] . HRMS (FAB) m/z: [M+Na] Calcd for
17 22 5
C H O SNa 361.1085; Found 361.1059.
3-O-Benzyl-1,2-O-isopropylidene-5-thio-α-D-xylofuranose (10). A solution of the thioace-
tate 16 (11.3 g, 33.4 mmol) in THF (50 mL) was added dropwise to a stirred suspension of LiAlH
4
(1.5 g, 39.4 mmol) in THF (50 mL) at 0 °C, and the mixture was stirred at 0 °C for 30 min. After
cooling, the excess of hydride was decomposed successively with EtOAc and water. The resulting
mixture was acidified with 10% hydrochloric acid (pH ca. 3) and extracted with EtOAc (2×100 mL,
1
×50 mL). The extract was washed with brine and condensed to give a pale yellow solid (10.1 g),
which on recrystallyzation from a mixture of n-hexane and EtOAc gave title compound 10 (8.56 g,
87%) as colorless needles. Column chromatography (n-hexane–acetone, 20:1) of the mother liquid
2
4
gave 10 (936 mg, 9%) as a pale yellow solid. Mp 54–56 °C. []
D
3
–84.5 (c 1.0, CHCl ). IR (KBr):
-1 1
2
974, 2935, 2573 (S–H), 1454, 1373, 1319, 1254, 1215, 1162, 1138, 1099, 1072, 1049, 1010 cm . H
NMR (500 MHz, CDCl
3
3 2
) : 1.32 (1H, t, J = 9.1, SH), 1.32/1.51 [each 3H, s, C(CH ) ], 2.76 (1H, ddd,
J = 13.1, 9.1, 8.3, H-5a), 2.81 (1H, ddd, J = 13.1, 9.1, 6.0, H-5b), 4.02 (1H, d, J = 3.2, H-3), 4.26 (1H,
ddd, J = 8.3, 6.0, 3.2, H-4), 4.50/4.72 (each 1H, d, J =11.8, CH Ph), 4.63 (1H, d, J = 3.9, H-2), 5.91
2
1
3
(
1H, d, J = 3.9, H-1), 7.29–7.38 (5H, m, arom.). C NMR (125 MHz, CDCl ) : 21.1 (C-5), 26.2/26.7
3
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[C(CH
)
], 71.9 (CH
Ph), 80.8 (C-3), 81.9 (C-2), 82.3 (C-4), 105.1 (C-1), 111.7 [C(CH
)
],
3
2
2
3
2
+
127.9/128.1/128.5 (d, arom.), 137.2 (s, arom.). HRMS (ESI) m/z: [M+Na] Calcd for C15
H O
20 4
SNa
319.0975; Found 319.0968.
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3-O-Benzyl-5-S-(3,4-di-O-benzyl-1-deoxy-L-erythritol-1-yl)-1,2-O-isopropylidene-5-
thio-D-xylofuranose (17). Under an Ar atmosphere, a mixture of 10 (1.02 g, 3.45 mmol), 1,2-
10
anhydro-3,4-di-O-benzyl-L-erythritol (11, 1.17 g, 4.12 mmol), NaOH (190 mg, 4.8 mmol), and EtOH
(
40 mL) was heated under reflux for 1.5 h. After being cooled, the reaction mixture was concentrated in
vacuo to give pale yellow oil, which was dispersed with water (20 mL) and the resulting mixture ex-
tracted with EtOAc (1×60 mL, 2×20 mL). The extract was washed with brine and condensed to give a
pale yellow oil (2.28 g), which on column chromatography (n-hexane-acetone, 50:1 → 20:1) gave title
2
5
compound 17 (1.8 g, 90%) as a pale yellow oil. []D –40.5 (c = 1.05, CHCl ). IR (neat): 3471, 2928,
3
-1
1
2866, 1454, 1373, 1215, 1165, 1076, 1026 cm . H NMR (500 MHz, CDCl
3
) : 1.31/1.48 [each 3H, s,
C(CH ], 1.60 (1H, br s, OH), 2.73 (1H, dd, J = 14.0, 8.3, H-1’a), 2.85 (1H, dd, J = 13.2, 7.1, H-5a),
3 2
)
2.88 (1H, dd, J = 13.2, 6.6, H-5b), 2.90 (1H, dd, J = 14.0, 3.4, H-1’b), 3.62 (1H, ddd, J = 6.0, 4.9, 4.3,
H-3’), 3.66 (1H, dd, J = 10.3, 4.9, H-4’a), 3.73 (1H, dd, J = 10.3, 4.3, H-4’b), 3.90 (1H, ddd, J = 8.3,
6
.0, 3.4, H-2’), 3.94 (1H, d, J = 3.1, H-3), 4.33 (1H, ddd, J = 7.1, 6.6, 3.1, H-4), 4.51/4.67 (each 1H, d,
J = 11.7, CH Ph), 4.54 (2H, s, CH Ph), 4.57/4.70 (each 1H, d, J = 11.4, CH Ph), 4.60 (1H, d, J = 4.0,
2
2
2
13
H-2), 5.90 (1H, d, J = 4.0, H-1), 7.25–7.35 (15H, m, arom.). C-NMR (125 MHz, CDCl
C(CH ], 30.5 (C-5), 37.0 (C-1’), 69.8 (C-4’), 70.8 (C-2’), 72.0/72.6/73.5 (CH Ph), 79.6 (C-3’), 80.3
(C-4), 81.8 (C-3), 82.0 (C-2), 105.0 (C-1), 111.6 [C(CH ],
27.67/127.71/127.91/127.94/128.36/128.41/128.5 (d, arom.), 137.3/138.0/138.2 (s, arom.). LRMS
3
) : 26.2/26.8
[
3
)
2
2
3 2
)
1
+
+
+
(FAB) m/z: 581 [M+H] , 603 [M+Na] . HRMS (FAB) m/z: [M+H] Calcd for C H O S 581.2573;
33 41 7
Found 581.2593.
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3-O-Benzyl-5-S-(3,4-di-O-benzyl-1-deoxy-L-erythritol-1-yl)-5-thio-D-xylitol (19). A mix-
ture of 17 (1.7 g, 2.93 mmol), 1,4-dioxane (20 mL), and 10% H SO (4 mL) was heated under reflux
for 1.5 h. After being cooled the reaction mixture was diluted with water (50 mL), and the resulting
mixture was neutralized with NaHCO . The mixture was extracted with EtOAc (1×50 mL, 2×30 mL).
2
4
0
1
2
3
4
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1
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The extract was washed with brine and evaporated to give 3-O-benzyl-5-S-(3,4-di-O-benzyl-1-deoxy-
L-erythritol-1-yl)-5-thio-D-xylitol (18) a pale yellow oil (1.64 g), which was then dissolved in metha-
nol (30 mL) and treated with NaBH
diluted with a mixture of acetone (1 mL) and water (5 mL) and condensed to give a pale yellow semi-
solid (1.92 g), which on column chromatography (CHCl -acetone, 50:1) gave title compound 19 (821
+91.2 (c 0.91, CHCl ). IR (neat): 3406, 2920, 2870,
454, 1396, 1365, 1311, 1257, 1211, 1091, 1072, 1026 cm . H NMR (500 MHz, CDCl ) : 2.72 (2H,
4
(220 mg, 5.8 mmol) at 0 °C for 1 h. The reaction mixture was
3
2
D
3
mg, 52% from 17) as a pale yellow oil. []
3
-1 1
1
3
br t-like, J = 6.9, H-5a and H-5b), 2.74 (1H, br dd, J = 13.2, 6.9, H-1’a), 2.84 (1H, br d-like, J = 13.2,
H-1’b), 3.58 (1H, dd, J = 4.6, 2.9, H-3), 3.60 (1H, dd, J = 11.8, 4.3, H-1a), 3.62 (1H, ddd, J = 6.9, 4.6,
4
.6, H-3’), 3.68 (1H, dd, J = 10.3, 4.6, H-4’a), 3.71 (1H, dd, J = 10.3, 4.6, H-4’b), 3.74 (1H, dd, J =
1.8, 4.6, H-1b), 3.84 (1H, ddd, J = 4.6, 4.6, 4.3, H-2), 3.91 (1H, ddd, J = 6.9, 6.9, 3.2, H-2’), 3.94 (1H,
1
ddd, J = 6.9, 6.9, 2.9, H-4), 4.53 (2H, s, CH
2
Ph), 4.55/4.67 (each 1H, d, J = 11.7, CH
2
Ph), 4.61/4.64
1
3
(
each 1H, d, J = 11.4, CH Ph), 7.25–7.35 (15H, m, arom.). C NMR (125 MHz, CDCl ) : 36.4 (C-
2
3
1
2
’), 36.8 (C-5), 62.6 (C-1), 69.7 (C-4’), 70.0 (C-4), 70.9 (C-2), 71.2 (C-2’), 72.6/73.5/74.4 (CH Ph),
79.2 (C-3’), 79.7 (C-3), 127.7/127.8/127.9/128.2/128.3/128.4/128.5/128.6 (d, arom.),
+
+
1
37.5/137.7/138.0 (s, arom). LRMS (FAB) m/z: 543 [M+H] , 565 [M+Na] . HRMS (FAB) m/z:
+
[
M+H] Calcd for C30
H
39
O
7
S 543.2417; Found 543.2403.
3-O-Benzyl-5-S-(3,4-di-O-benzyl-1-deoxy-L-erythritol-1-yl)-1,2-O-isopropylidene-5-
thio-D-xylitol (20). To a mixture of 19 (582 mg, 0.93 mmol), 2,2-dimethoxypropane (2,2-DMP, 1.15
mL, 9.4 mmol) and acetone (7 mL) was added p-toluenesulfonic acid (PTSA, 40 mg) at 0 °C, and the
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mixture was stirred at room temperature for 3 h. The reaction mixture was poured into aqueous Na-
HCO (30 mL) and extracted with EtOAc (1×30 mL, 2×10 mL). The extract was washed with brine
and condensed to give a colorless oil (674 mg), which on column chromatography (n-hexane-EtOAc,
3
0
1
2
3
4
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30:1 → 10:1) gave title compound 20 (390 mg, 62%) as a colorless oil. []
D
+1.13 (c 0.96, CHCl
IR (neat): 3445, 2916, 2870, 1454, 1369, 1254, 1211, 1076, 1029 cm . H NMR (800 MHz, CDCl ) :
], 2.67 (1H, dd, J = 13.6, 5.6, H-5a), 2.69 (1H, dd, J = 13.6, 7.2, H-5b),
3
).
-1
1
3
1
2
3
3 2
.38/1.44 [each 3H, s, C(CH )
.70 (1H, dd, J = 13.6, 8.0 Hz, H-1’a), 2.83 (1H, dd, J = 13.6, 3.2, H-1’b), 2.96 (1H, d, J = 6.4, OH),
.13 (1H, d, J = 4.0, OH), 3.52 (1H, dd, J = 6.4, 2.4, H-3), 3.61 (1H, ddd, J = 6.4, 4.0, 4.0, H-3’), 3.65
(
1H, dddd-like, J = 7.2, 6.4, 5.6, 2.4, H-4), 3.69 (1H, dd, J = 10.4, 4.0, H-4’a), 3.72 (1H, dd, J = 10.4,
4.0, H-4’b), 3.74 (1H, dd, J = 8.0, 7.2, H-1a), 3.88 (1H, dddd-like, J = 8.0, 6.4, 4.0, 3.2, H-2’), 4.03
1H, dd, J = 8.0, 6.4, H-1b), 4.37 (1H, ddd, J = 7.2, 6.4, 6.4, H-2), 4.54/4.55 (each 1H, d, J = 12.0,
CH Ph), 4.56/4.69 (each 1H, d, J = 11.2, CH Ph), 4.65/4.85 (each 1H, d, J = 11.2, CH Ph), 7.27–7.35
(15H, m, arom.). C NMR (200 MHz, CDCl ) : 25.5/26.6 [C(CH ], 36.6 (C-1’), 36.9 (C-5), 66.0
C-1), 69.8 (C-4’), 71.0 (C-4), 71.2 (C-2’), 72.6/73.5/74.1 (CH Ph), 77.2 (C-2), 79.2 (C-3’), 79.6 (C-3),
09.3 [C(CH ], 127.7/127.8/127.89/127.90//128.3/126.39/128.44 (d, arom.), 137.8/138.00/138.04 (s,
arom.). LRMS (FAB) m/z: 583 [M+H] , 605 [M+Na] . HRMS (FAB) m/z: [M+H] Calcd for
S 583.2729; Found 583.2734.
(
2
2
2
1
3
3
3 2
)
(
2
1
3 2
)
+
+
+
33 43 7
C H O
3,4-Di-O-benzyl-5-S-(2,3,4-tri-O-benzyl-1-deoxy-L-erythritol-1-yl)-1,2-O-
isopropylidene-5-thio-D-xylitol (21). A solution of 20 (276 mg, 0.47 mmol) in DMF (4 mL) was
added dropwise to a mixture of NaH (40 mg, 1.0 mmol, 60% in liquid paraffin), benzyl bromide (125
l, 1.1 mmol), and DMF (2 mL) at 0°C. After being stirred at 0 °C for 1 h, the mixture was poured into
cold water (30 mL) and extracted with EtOAc (1×30 mL, 2×10 mL). The extract was washed with
brine and condensed to give a pale yellow oil (492 mg), which on column chromatography (n-hexane-
25
EtOAc, 30:1 → 10:1) gave title compound 21 (334 mg, 93%) as a colorless oil. []
D
–21.6 (c 1.02,
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3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
-
1 1
CHCl
3
3
). IR (neat): 2866, 1496, 1454, 1369, 1253, 1211, 1091, 1072, 1026 cm . H NMR (500 MHz,
CDCl
) : 1.35/1.39 [each 3H, s, C(CH ], 2.77 (1H, dd, J = 13.5, 6.6, H-5a), 2.81 (1H, d-like, J = ca.
3 2
)
4
.0, H-1’a and H-1’b), 2.88 (1H, dd, J = 13.5, 6.0, H-5b), 3.49 (1H, ddd, J = 8.3, 6.3, 3.5, H-2), 3.53
(1H, dd, J = 8.3, 8.0, H-1a), 3.58 (1H, dd, J = 7.2, 3.5, H-3), 3.64 (1H, dd, J = 10.6, 4.6, H-4’a), 3.66
1H, dd, J = 8.3, 6.3, H-1b), 3.70 (1H, dd, J = 10.6, 3.2, H-4’b), 3.77–3.83 (2H, m, H-2’ and H-3’),
.27 (1H, ddd, J = 7.2, 6.6, 6.0, H-4), 4.33/4.55 (each 1H, d, J = 11.7, CH Ph), 4.51 (2H, s, CH Ph),
4.52/4.62 (each 1H, d, J = 11.4, CH Ph), 4.59/4.71 (each 1H, d, J = 11.4, CH Ph), 4.65/4.79 (each 1H,
d, J = 11.7, CH Ph), 7.23–7.34 (30H, m, arom.). C NMR (125 MHz, CDCl ) : 25.7/26.6 [C(CH ],
3.1 (C-5), 34.2 (C-1’), 65.9 (C-1), 69.2 (C-4’), 72.1/72.5/72.7/73.3/74.0 (CH Ph), 77.1 (C-4), 78.77,
78.82, 78.9 (C-2’, C-3’ and C-2), 79.0 (C-3), 108.9 [C(CH ],
27.6/127.7/127.8/127.9/128.16/128.22/128.25/128.30/128.34 arom.),
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
4
2
2
2
2
13
2
3
3 2
)
3
2
3 2
)
1
1
(d,
+
+
37.8/138.1/138.2/138.42/138.5 (s, arom.). LRMS (FAB) m/z: 763 [M+H] , 785 [M+Na] . HRMS
+
(FAB) m/z: [M+Na] Calcd for C47
H
54
O
7
SNa 785.3489; Found 785.3488.
3,4-Di-O-benzyl-5-S-(2,3,4-tri-O-benzyl-1-deoxy-L-erythritol-1-yl)-5-thio-D-xylitol (22).
A mixture of 21 (300 mg, 0.39 mmol), 10% hydrochloric acid (0.5 mL), and methanol (2.5 mL) was
heated at 60 ° for 1 h. After being cooled, the reaction mixture was poured into cold water (25 mL).
3
The resulting mixture was neutralized with NaHCO and extracted with EtOAc (1×30 mL, 2×10 mL).
The extract was washed with brine and condensed to give a pale yellow oil (285 mg), which was pure
enough for the next reaction. For analytical purpose a small portion was purified by means of column
2
5
chromatography (n-hexane-EtOAc, 15:1) to give title compound 22 as a colorless oil. []
.1, CHCl
NMR (500 MHz, CDCl
D
+62.5 (c
-1 1
0
3
). IR (neat): 3441, 2920, 2870 1497, 1454, 1396, 1362, 1207, 1095, 1072, 1026 cm . H
3
) : 2.13 (1H, br s, OH), 2.54 (1H, d, J = 5.5 OH), 2.83 (1H, dd, J = 13.5, 6.6,
H-5a), 2.88 (2H, d-like, J = ca. 5.5, H-1’a and H-1’b), 2.90 (1H, dd, J = 13.5, 5.2, H-5b), 3.49 (2H, br
d-like, J = ca. 4.3, H-1a and H-1b), 3.64 (1H, dd, J = 5.2, 4.6, H-3), 3.65 (1H, dd, J = 10.3, 4.9, H-4’a),
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9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
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4
5
5
5
5
5
5
5
5
5
5
6
3.71 (1H, dd, J = 10.3, 3.2, H-4’b), 3.71—3.75 (1H, m, H-2), 3.79 (1H, ddd, J = 6.6, 5.2, 5.2 Hz, H-4),
13
3
.80–3.86 (2H, m, H-2’ and H-3’), 4.46–4.73 (10H, m, CH
125 MHz, CDCl
72.5/72.7/72.8/73.3/74.5 (CH
27.56/127.60/127.63/127.66/127.79/127.84/127.88/128.0/128.23/128.30/128.34/128.4/128.5
2
Ph), 7.23–7.34 (25H, m, arom.). C NMR
(
3
) : 33.6 (C-5), 34.4 (C-1’), 64.0 (C-1), 69.2 (C-4’), 70.9 (C-2),
Ph), 78.7, 78.8 (C2’, C3’), 79.1 (C-4), 79.2 (C-3),
(d,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
1
+
+
arom.), 137.7/137.8/138.1/138.4 (s, arom.). LRMS (FAB) m/z: 723 [M+H] , 745 [M+Na] . HRMS
+
(FAB) m/z: [M+H] Calcd for C44
H
51
O
7
S 723.3356; Found 723.3358.
3,4-Di-O-benzyl-5-S-(2,3,4-tri-O-benzyl-1-deoxy-L-erythritol-1-yl)-1-O-(tert-
butyldiphenylsilyl)-5-thio-D-xylitol (23). A mixture of 22 (265 mg, 0.37 mmol), tert-
butyldiphenylsilyl chloride (142 L, 0.55 mmol), imidazole (75 mg, 1.1 mmol), and DMF (2 mL) was
heated at 50 °C for 2 h. The reaction mixture was poured into cold water (10 mL) and extracted with
EtOAc (1×30 mL, 2×10 mL). The extract was washed with brine and condensed to give a colorless oil
(423 mg), which on column chromatography (n-hexane-acetone, 30:1 → 10:1) gave title compound 23
2
5
(
338 mg, 96% from 21) as a colorless oil. []
589, 1496, 1454, 1427, 1361, 1207, 1111, 1072, 1026 cm . H-NMR (500 MHz, CDCl
s, [C(CH ] ), 2.40 (1H, d, J = 6.6, OH), 2.84 (1H, dd, J = 13.8, 6.6, H-5a), 2.87 (1H, dd, J = 13.7, 6.0,
H-1’a), 2.89 (1H, dd, J = 13.8, 5.2, H-5b), 2.91 (1H, dd, J = 13.8, 4.0, H-1’b), 3.58 (1H, dd, J = 10.0,
.9, H-1a), 3.64 (1H, dd, J = 10.0, 6.1, H-1b), 3.65 (1H, dd, J = 10.6, 4.9, H-4’a), 3.71 (1H, dd, J =
10.6, 3.2, H-4’b), 3.79 (1H, ddd-like, J = ca. 6.6, 5.4, 5.2, H-4), 3.80–3.85 (2H, m, H-2’ and H-3’),
D
–2.74 (c = 1.21, CHCl
3
). IR (neat): 3475, 2928, 2859,
-1 1
1
3
) : 1.04 (9H,
3 3
)
6
3
.86 (1H, dddd-like, J = ca. 6.9, 6.6, 6.1, 2.3, H-2), 3.89 (1H, dd, J = 5.4, 2.3, H-3), 4.47–4.72 (10H, m,
1
3
CH
2
Ph), 7.17–7.65 (35H, m, arom.). C-NMR (125 MHz, CDCl
], 34.1 (C-5), 34.4 (C-1’), 64.6 (C-1), 69.3 (C-4’), 71.0 (C-2), 72.5/72.7/72.9/73.3/74.6
77.8 (C-3), 78.6, 79.0 (C-2’, C-3’), 79.7 (C-2),
27.5/127.55/127.58/127.61/127.64/127.73/127.8/127.91/127.93/128.1/128.27/128.32/129.74/135.6 (d,
3
) : 19.2 [SiC(CH
3 3
) ], 26.9
3 3
[SiC(CH )
(
2
CH Ph),
1
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2
2
2
2
2
2
2
3
3
3
3
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4
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4
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5
5
5
5
5
5
5
5
5
5
6
+
arom.) 133.15/133.21/138.0/138.21/138.24/138.5 (s, arom.). LRMS (FAB) m/z: 961 [M+H] , 983
+
+
[
69 7
M+Na] . HRMS (FAB) m/z: [M+H] Calcd for C60H O SSi 961.4533; Found 961.4503.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
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6
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9
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4
5
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7
8
9
0
3,4-Di-O-benzyl-5-S-(2,3,4-tri-O-benzyl-1-deoxy-L-erythritol-1-yl)-1-O-(tert-
butyldiphenylsilyl)-2-O-methansulfonyl-5-thio-D-xylitol (9). To a mixture of 23 (254 mg, 0.26
mmol), Et N (150 L, 1.08 mmol), Me N•HCl (10 mg, 0.10 mmol), and CH Cl (2.5 mL) was added
3
3
2
2
methanesulfonyl chloride (37 L, 0.48 mmol) at 0 °C. After being stirred at 0 °C for 2 h, the reaction
mixture was poured into cold water (10 mL) and extracted with EtOAc (1×30 mL, 2×10 mL). The ex-
tract was washed with brine and condensed in vacuo at below 20 °C to give a a pale yellow oil, (278
mg), which on column chromatography (n-hexane-acetone, 30:1 → 10:1) gave title compound 9 as a
-1
colorless oil (269 mg, 95%). IR (neat): 2990, 2859, 1497, 1454, 1358, 1207, 1177, 1111, 1072 cm .
1
H NMR (500 MHz, CDCl
3
) : 1.03 (9H, s,[C(CH
3
)
3
]), 2.78 (1H, dd, J = 13.8, 5.4, H-1’a), 2.79 (1H,
CH ), 2.88 (1H, dd, J =
dd, J = 13.5, 8.0, H-5a), 2.84 (1H, dd, J = 13.8, 3.8, H-1’b), 2.85 (3H, s, SO
2
3
13.5, 5.2, H-5b), 3.64 (1H, dd, J = 12.0, 5.2, H-1a), 3.66 (1H, dd, J = 10.3, 5.0, H-4’a), 3.67 (1H, ddd-
like, J = ca. 8.0, 5.2, 3.2, H-4), 3.70 (1H, dd, J = 10.3, 3.2, H-4’b), 3.78–3.85 (2H, m, H-2’ and H-3’),
3
.92 (1H, dd, J = 12.0, 2.9, H-1b), 4.16/4.44 (each 1H, d, J = 11.5, CH
H-3), 4.51 (2H, s-like, CH Ph), 4.54/4.62 (each 1H, d, J = 11.5, CH Ph), 4.56/4.70 (each 1H, d, J =
Ph), 4.78 (1H, ddd, J = 6.9, 5.2, 2.9, H-2), 7.08–
2
Ph), 4.18 (1H, dd, J = 6.9, 3.2,
2
2
1
1.5, CH
2
Ph), 4.65/4.66 (each 1H, d, J = 11.5, CH
2
13
7
.65 (35H, m, arom.). C NMR (125 MHz, CDCl ) : 19.2 [C(CH ) ], 26.9 [C(CH ) ], 32.3 (C-5),
3
3 3
3 3
34.1 (C1’), 38.2 (SO
2
CH
3
), 63.1 (C-1), 69.3 (C4’), 71.8/72.6/72.8/73.3/75.1 (CH
2
Ph), 76.9 (C-3), 77.1
(
C-4),
78.9/79.0
(C2’ and C3’),
83.5
(C-2),
1
27.55/127.59/127.7/127.79/127.82/127.9/127.8/128.2/128.29/128.31/128.35/128.44/129.9/130.0/135.
5
/135.6 (d, arom.), 132.5/132.9/137.4/137.6/138.17/138.24/138.5 (s, arom.). LRMS (FAB) m/z: 1039
+
+
71 9 2
[M+H] . HRMS (FAB) m/z: [M+H] Calcd for C61H O S Si 1039.4309; Found 1039.4298.
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5
5
6
Cyclization of Mesylate (9). A solution of 9 (244 mg, 0.24 mmol) in ethanol (8 mL) was heated
under reflux for 3 h. Removal of the solvent in vacuo left a pale yellow oil (245 mg), which on column
3 3
chromatography (CHCl → CHCl -MeOH, 50:1 → 30:1 →10:1) gave 2,3,-di-O-benzyl-5-O-(tert-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
butyldiphenylsilyl)-1,4-dideoxy-1,4-{(R)-[4-deoxy-1,2,3-tri-O-benzyl-D-erythritol-1-
yl]episulfoniumylidene}-D-arabinitol methanesulfonate (-24, 208 mg, 85%) and a ca. 1:3.5 mixture
of -24 and its -isomer -24 (11.7 mg, 5%).
2
4
Major isomer -24. Colorless oil. []D +36.0 (c 0.92, CHCl ). IR (neat): 2931, 28656, 1496,
3
-1
1
1
454, 1392, 1362, 1323, 1312, 1207, 1111, 1041 cm . H NMR (800 MHz, CDCl ) : 1.00 (9H, s,
3
–
[C(CH
3
)
3
]), 2.72 (3H, s, OSO
2
CH
3
), 3.63 (1H, dd, J = 13.6, 2.4, H-1a), 3.64 (1H, dd, J = 10.4, 4.8, H-
4
’a), 3.75 (1H, dd, J = 13.6, 4.0, H-1b), 3.78 (1H, dd, J = 10.4, 5.6, H-4’b), 3.87 (1H, dd, J = 10.4, 8.0,
H-5a), 3.93 (1H, ddd, J = 5.6, 4.8, 3.2, H-3’), 4.01 (1H, dd, J = 10.2, 6.4, H-5b), 4.19 (1H, dd, J = 13.6,
.4, H-1’a), 4.26 (1H, dd, J = 13.6, 4.0, H-1’b), 4.25/4.30 (each 1H, d, J = 12.0, CH Ph), 4.36 (1H, dd,
J = 2.4, 1.6, H-3), 4.38 (1H, ddd, J = 6.4, 4.0, 3.2, H-2’) 4.44 (1H, ddd, J = 4.0, 2.4, 2.4, H-2), 4.48
1H, br dd-like, J = ca. 8.0, 6.4, H-4), 4.49 (2H, s, CH Ph), 4.51/4.520 (each 1H, d-like, J = 12.0,
CH Ph), 4.524/4.58 (each 1H, d, J = 12.0, CH Ph), 4.56/4.63 (each 1H, d, J = 12.0 Hz, CH
7.55 (35H, m, arom.). C NMR (200 MHz, CDCl ) : 19.2 [C(CH ], 26.8 [C(CH
OSO CH
CH Ph), 76.0 (C-2’), 76.9 (C-3’), 82.7 (C-2), 82.8 (C-3), 127.7/127.79/127.83/
6
2
(
2
2
2
2
Ph), 7.05–
1
3
–
3
3
)
3
3 3
) ], 39.6 (
2
3
), 48.1 (C-1’), 48.5 (C-1), 61.4 (C-5), 65.2 (C-4), 68.7 (C-4’), 71.7/71.9/72.4/72.6/73.4
(
2
127.88/127.93/127.97/128.0/128.1/128.2/128.3/128.36/128.39/128.54/128.58/128.64/130.07/130.11/1
+
3
5.50/135.53 (d, arom.), 132.1/132.2/136.2/136.4/137.1/137.7/137.9 (s, arom). LRMS (FAB ) m/z:
+
+
+
9
3 3 3 3 67 6
43 [M–CH SO ] . HRMS (FAB ) m/z: [M–CH SO ] Calcd for C60H O SSi 943.4428; Found
943.4455.
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5
5
5
5
5
5
6
NMR data for minor isomer -24 extracted from the spectrum of a mixture (/ = ca.
1
1
:3.5). H NMR (800 MHz, CDCl
3
3 3 2 3
) : 0.97 [9H, s, C(CH ) ], 2.75 (3H, s, SO CH ), 3.45 (1H, dd, J =
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
10.4, 4.8, H-4’a), 3.57 (1H, dd, J = 10.4, 5.6, H-4’b), 3.76 (1H, dd-like, J = ca. 9.6, 5.6, H-4), 3.81 (1H,
dd, J = 13.6, 3.2, H-1’a), 3.85 (1H, ddd, J = 5.6, 4.8, 2.4, H-3’), 3.88 (1H, dd, J = 15.2, 4.0, H-1a),
3
.93 (1H, dd, J = 10.4, 9.6, H-5a), 4.12 (1H, dd, J = 13.6, 4.0, H-1’b), 4.23 (1H, dd, J = 10.4, 5.6, H-
b), 4.27 (2H, s, CH Ph), 4.30/4.38 (each 1H, d, J = 12.0, CH Ph), 4.34 (1H, br s, H-3), 4.35/4.37
Ph), 4.36 (1H, br s-like, H-2), 4.45 (1H, br dd-like, J = ca. 15.2, 2.0,
H-1b), 4.47 (1H, m, H-2’), 4.53/4.54 (each 1H, d-like, J = 12.0, CH Ph), 4.57/4.59 (each 1H, d, J =
Ph), 7.26–7.51 (35H, m, arom.). C NMR (200 MHz, CDCl ) : 19.0 [C(CH ], 26.7
], 39.6 (SO CH ), 41.3 (C-1’), 46.3 (C-1), 60.2 (C-5), 61.7 (C-4), 68.9 (C-4’),
1.3/71.7/72.4/73.1/73.4 (CH Ph), 76.2 (C-2’), 76.5 (C-3’), 82.0 (C-2), 84.3 (C-3),
27.57/127.6/127.9/128.20/128.23/128.24/128.3/128.4/128.61/128.64/128.7/130.2/135.4/135.5 (d,
5
2
2
(
each 1H, d-like, J = ca. 12.0, CH
2
2
1
3
1
2.0, CH
2
3
3 3
)
[
C(CH
3
)
3
2
3
7
1
2
arom.), 131.9/ 132.1/136.17/136.22/137.2/137.87/137.90 (s, arom.).
Neosalacinol Methanesulfonate (4, X = OMs). A suspension of 10% palladium-on-carbon
(
200 mg) in 20% aqueous triflacetic acid (4 mL) was pre-equilibrated with hydrogen. To the suspen-
sion was added a solution of -24 (191 mg, 0.18 mmol) in EtOAc (2 mL), and the mixture was hydro-
genated at room temperature under atmospheric pressure until the uptake of hydrogen ceased. The
catalyst was filtered off, and the catalyst was washed with methanol. The combined filtrate and wash-
ings were condensed in vacuo. The residue (64 mg) was purified by means of column chromatography
(
[
3 3
CHCl →CHCl -MeOH→10:1→3/1) to give title compound 4 (52.5 mg, 90%) as a colorless oil.
2
D
2
-1 1
]
+4.77 (c 1.50, CH
3
OH). IR (neat): 3321, 1415, 1335, 1207, 1192, 1072, 1041 cm . H NMR
-
(800 MHz, CD
3
OD) : 2.70 (3H, s, CH
3
SO
3
), 3.60 (1H, ddd, J = 6.4, 4.8, 4.0, H-3’), 3.62 (1H, dd, J =
1
1.2, 4.8, H-4’a), 3.69 (1H, dd, J = 11.2, 4.0, H-4’b), 3.73 (1H, dd, J = 12.8, 8.8, H-1’a), 3.85 (1H, dd,
J = 12.8, 3.2, H-1’b), 3.86 (2H, m, H-1a and H-1b), 3.92 (1H, dd, J =11.2, 8.8, H-5a), 4.01 (1H, br dd,
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J = 8.8, 5.6, H-4), 4.05 (1H, dd, J = 11.2, 5.6, H-5b), 4.08 (1H, ddd, J = 8.8, 6.4, 3.2, H-2’), 4.37 (1H,
13
dd, J = 2.4, 1.6, H-3), 4.62 (1H, ddd-like, J = 2.4, 2.4, 2.4, H-2). C NMR (200 MHz, CDCl
3
) : 39.5
-
(
CH
3
SO
3
), 51.8 (C-1’), 52.0 (C-1), 61.1 (C-5), 64.0 (C-4’), 69.6 (C-2’), 73.7 (C-4), 75.3 (C-3’), 79.45
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
–
3 3 3 3
(C-2), 79.53 (C-3). LRMS (FAB) m/z: 255 [M–CH SO ] , 95 [CH SO ] . HRMS (FAB) m/z: [M–
+
CH
3
SO
3
] Calcd for C
9
H
19
O
6
S 255.0902; Found 255.0901.
Ion exchange reaction of 4 (X = OMs). A mixture of 4 (X = OMs, 16 mg, 0.046 mmol), ion
-
exchange resin IRA-400J (Cl form, 1 g), and methanol (3 mL) was stirred at room temperature for 12
h. The resin was filtered off, and the filtrate was evaporated to give a pale yellow oil (15 mg), which
on column chromatography (CHCl →CHCl -MeOH→10:1→3/1) gave the corresponding chloride 4
3
3
8
e
(
X = Cl, 11.7 mg, 89%). The spectral properties of 4 agreed well with those reported.
Benzyl
2,3,4-Tri-O-benzyl-6-S-(3-O-benzyl-1,2-di-O-isopropylidene-5-deoxy--D-
xylofuranos-5-yl)-6-thio--D-glucopyranoside (26). A mixture of benzyl 2,3,4-tri-O-benzyl-6-
11
O-(p-toluenesulfonyl)--D-glucopyranoside (25, 4.54 g, 6.5 mmol), thiol 10 (2.03 g, 6.9 mmol),
NaOH (533 mg, 13.3 mmol), and EtOH (60 mL) was heated under reflux for 3 h. After being cooled,
the reaction mixture was condensed in vacuo and the residue was diluted with water (100 mL), and the
resulting mixture was extracted with EtOAc (1×200 mL, 2×50 mL). The extract was washed with
brine and condensed to give a pale brown solid (5.6 g), which on recrystallization from methanol gave
title compound 26 (4.61 g, 91%) as colorless needles. Column chromatography (n-hexane–EtOAc,
2
D
4
10/1→5/1) of the mother liquid gave 26 (310 mg, 6%) as a colorless solid. Mp. 120–121 °C. []
–
-
1 1
4
7.6 (c = 1.37, CHCl
) : 1.31/1.49 [each 3H, s, C(CH
2.96 (1H, dd, J = 13.6, 5.6, H-5a), 2.976 (1H, dd-like, J = ca. 13.6, 2.4, H-6’b), 2.982 (1H, dd, J = 13.6,
.0, H-5b), 3.46 (1H, dd, J = 9.6, 9.6, H-4’), 3.45–3.48 (1H, m, H-5’), 3.50 (1H, dd, J = 9.6, 8.0, H-2’),
3
). IR (KBr): 3032, 2920, 2854, 1454, 1361, 1319, 1215, 1080 cm . H NMR
(
800 MHz, CDCl
3
3 2
)
], 2.72 (1H, dd-like, J = ca. 13.6, 8.0, H-6’a),
8
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3.62 (1H, dd, J = 9.6, 9.6, H-3’), 4.00 (1H, d, J = 3.2, H-3), 4.40 (1H, ddd, J = 8.0, 5.6, 3.2 H-4), 4.48
1H, d, J = 8.0, H-1), 4.54/4.66 (each 1H, d, J = 11.2, CH Ph), 4.590/4.86 (each 1H, d, J = 11.2,
CH Ph), 4.596 (1H, d, J = 3.2, H-2), 4.63/4.914 (each 1H, d, J = 12.0, CH Ph), 4.70/4.94 (each 1H, d,
J = 11.2, CH Ph), 4.00 (1H, d, J = 3.2, H-1), 7.24–7.38
], 31.0 (C-5), 34.5 (C-6’),
Ph), 75.8 (C-5’), 80.2 (C-4), 80.3 (C-4’), 81.9 (C-3), 82.1 (C-2), 82.5
102.2 (C-1’), 105.1 (C-1), 111.6 [C(CH ],
(
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
Ph), 4.76/4.918 (each 1H, d, J = 10.4, CH
2
13
(
25H, m, arom.). C-NMR (200 MHz, CDCl
3
3 2
) : 26.2/26.8 [C(CH )
7
1.0/72.2/74.8/75.1/75.7 (CH
2
(C-2’),
84.6 (C-3’),
3 2
)
127.60/127.62/127.71/127.75/127.85/127.86/127.89/128.0/128.1/128.2/128.31/128.35/128.37/128.43/
+
1
28.45 (d, arom.), 137.3/137.5/138.0/138.4/138.5 (s, arom.). LRMS (FAB) m/z: 841 [M+Na] . HRMS
+
(FAB) m/z: [M+Na] Calcd for C49
H
54
O
9
SNa 841.3386; Found 841.3382.
Benzyl
glucopyranoside (27). A mixture of 26 (4.61 g, 5.6 mmol), trifluoroacetic acid (TFA, 18 mL), THF
36 mL), and water (9 mL) was heated at 90 ° for 4 h. After being cooled the reaction mixture was
diluted with water (100 mL), and the resulting mixture was extracted with CHCl (1×100 mL, 2×50
mL). The extract was successively washed with aqueous NaHCO and brine, and condensed to give a
pale yellow oil (4.54 g), which was then dissolved in a mixture of THF and water (150 mL, 2/1, v/v)
and treated with NaBH (1.04 g, 28 mmol) at 0 °C for 4 h. The reaction mixture was poured into water
150 mL), and the resulting mixture was extracted with EtOAc (1×100 mL, 2×50 mL). The extract was
2,3,4-Tri-O-benzyl-6-S-(3-O-benzyl-5-deoxy--D-xylitol-5-yl)-6-thio--D-
(
3
3
4
(
washed with and brine and condensed to give a pale yellow viscous oil, (4.56 g), which on column
chromatography (n-hexane-EtOAc, 10:1 → 3:1) gave title compound 27 (3.81 g, 87%) as a colorless
2
3
waxy solid. Mp. 96–97 °C. []D +1.37 (c = 1.67, CHCl ). IR (KBr): 3412, 3032, 2924, 2873, 1497,
3
-
1 1
1
454, 1357, 1311, 1281, 1227, 1076, 1030 cm . H NMR (800 MHz, CDCl
ca. 8.0, 4.0, OH), 2.75 (1H, d, J = 6.4, OH), 2.77 (1H, dd, J = 14.4, 8.0, H-5a), 2.82 (1H, dd-like, J =
4.4, 6.4, H-6’a), 2.86 (1H, dd, J = 14.4, 5.6, H-5b), 2.90 (1H, dd, J = 14.4, 2.4, H-6’b), 3.17 (1H, d, J
3
) : 2.74 (1H, dd-like, J =
1
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5
5
6
= 5.6, OH), 3.49 (1H, ddd, J = 9.6, 6.4, 2.4, H-5’), 3.52 (1H, dd-like, J = 8.8, 8.0, H-2’), 3.57 (1H, dd,
J = 8.8, 8.8, H-4’), 3.61 (1H, ddd-like, J = ca. 12.0, 8.0, 4.0, H-1a), 3.638 (1H, dd, J = 8.8, 8.8, H-3’),
3
.640 (1H, dd, J = 4.0, 3.2, H-3), 3.77 (1H, ddd, J = 12.0, 4.0, 4.0, H-1b), 3.84 (1H, ddt, J = 6.4, 4.0,
4.0, H-2), 4.00 (1H, dddd, J = 8.0, 5.6, 5.6, 3.2, H-4), 4.52 (1H, d, J = 8.0, H-1’), 4.61/4.89 (each 1H, d,
J = 10.4, CH Ph), 4.64/4.65 (each 1H, d, J = 12.0, CH Ph), 4.66/4.944 (each 1H, d, J = 12.0, CH Ph),
.72/4.948 (each 1H, d, J = 11.2, CH Ph), 4.77/4.93 (each 1H, d, J = 11.2, CH Ph), 7.23–7.39 (25H, m,
) : 34.1 (C-6’), 37.6 (C-5), 62.4 (C-1), 69.6 (C-4), 70.6 (C-2),
Ph), 75.0 (C-5’), 79.6 (C-3), 79.7 (C-4’), 82.3 (C-2’), 84.4 (C-3’), 102.4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
2
2
4
2
2
1
3
arom.). C-NMR (125 MHz, CDCl
3
71.3/74.4/74.9/75.2/75.7 (CH
2
(
C-1’),
127.7/127.86/127.90/128.0/128.1/128.2/128.3/128.39/128.45/128.50/128.6
(d,
arom.),
+
137.1/137.5/137.9/138.2/138.4 (s, arom.). LRMS (FAB) m/z: 803 [M+Na] . HRMS (FAB) m/z:
+
[
M+Na] Calcd for C46
H
52
O
9
SNa 803.3230; Found 803.3256.
Benzyl 2,3,4-Tri-O-benzyl-6-S-(3-O-benzyl-1,2-O-isopropylidene-5-deoxy--D-xylitol-
5-yl)-6-thio--D-glucopyranoside (28). To a mixture of 27 (3.48 g, 4.46 mmol), 2,2-
dimethoxypropane (2,2-DMP, 1.1 mL, 9.0 mmol) acetone (30 mL) was added p-toluenesulfonic acid
(
PTSA, 24 mg, 0.14 mmol) at 0 °C, and the mixture was stirred at room temperature for 1 h. To the
reaction mixture was added aqueous NaHCO and the resulting mixture was extracted with EtOAc
3
(1×50 mL, 2×20 mL). The extract was washed with brine, and condensed to give a colorless viscous
oil (3.67 g), which on column chromatography (n-hexane-EtOAc, 50:1 → 5:1) gave title compound 28
2
4
(
3.11 g, 85%) as a colorless viscous oil. []
D
–14.8 (c = 1.55, CHCl
3
). IR (neat): 3460, 3032, 2909,
877, 1497, 1454, 1369, 1250, 1211, 1072, 1030 cm . H NMR (500 MHz, CDCl ) : 1.38/1.45 [each
H, s, C(CH ], 2.74 (1H, dd, J = 14.0, 6.6, H-6’a), 2.76 (2H, d, J = 6.6, H-5a and H-5b), 2.85 (1H, d,
-1 1
2
3
3
3 2
)
J = 6.6, OH), 2.89 (1H, dd, J = 14.0, 2.3, H-6’b), 3.46 (1H, ddd, J = 9.7, 6.6, 2.3, H-5’), 3.498 (1H, dd,
J = 9.2, 7.8, H-2’), 3.504 (1H, dd, J = 9.7, 9.7, H-4’), 3.55 (1H, dd, J = 6.9, 2.3, H-3), 3.63 (1H, dd, J =
9
.7, 9.2, H-3’), 3.66 (1H, dtd, J = 6.6, 6.6, 2.3, H-4), 3.74 (1H, dd, J = 8.3, 8.1, H-1a), 4.04 (1H, dd, J
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6
= 8.3, 6.6, H-1b), 4.41 (1H, ddd-like, J = 8.1, 6.9, 6.6, H-2), 4.51 (1H, d, J = 7.8, H-1’), 4.59/4.88
each 1H, d, J = 10.9, CH Ph), 4.64/4.926 (each 1H, d, J = 11.8, CH Ph), 4.66/4.86 (each 1H, d, J =
1.5, CH Ph), 4.71/4.95 (each 1H, d, J = 10.9, CH Ph), 4.77/4.928 (each 1H, d, J = 10.9, CH Ph),
7.23–7.39 (25H, m, arom.). C-NMR (125 MHz, CDCl ) : 25.6/26.6 [C(CH ], 34.2 (C-6’), 37.5
C-5), 66.1 (C-1), 70.9 (C-4), 71.2/74.5/74.9/75.2/75.7 (CH Ph), 75.3 (C-5’), 77.4 (C-2), 79.6 (C-3),
9.9 (C-4’), 82.4 (C-2’), 84.5 (C-3’), 102.4 (C-1’), 109.3 [C(CH ],
(
2
2
1
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
3
3 2
)
(
2
7
3 2
)
127.6/127.7/127.83/127.85/127.91/128.01/128.05/128.13/ 128.26/128.33/128.37/128.42/128.5 (d,
+
arom.), 137.1/137.9/138.1/138.3/138.4 (s, arom.). LRMS (FAB) m/z: 843 [M+Na] . HRMS (FAB)
+
m/z: [M+Na] Calcd for C49
H
56
O
9
SNa 843.3543; Found 843.3563.
Benzyl
2,3,4-Tri-O-benzyl-6-S-(3,4-di-O-benzyl-1,2-O-isopropylidene-5-deoxy--D-
xylitol-5-yl)-6-thio--D-glucopyranoside (29). A solution of 28 (3.0 g, 3.8 mmol) in DMF (20
mL) was added dropwise to a mixture of NaH (310 mg, 7.8 mmol, 60% in liquid paraffin), benzyl bro-
mide (0.7 mL, 5.9 mmol), and DMF (5 mL) at 0°C, and the mixture was stirred at room temperature for
2
1
h. The reaction mixture was poured into cold water (150 mL) and extracted with EtOAc (2×50 mL,
×30 mL). The extract was washed with brine and condensed to give a colorless oil (3.75 g), which on
column chromatography (n-hexane-EtOAc, 50:1 → 10:1) gave title compound 29 (3.05 g, 87%) as a
2
3
colorless viscous oil. []
D
–30.3 (c = 1.56, CHCl
211, 1069, 1030 cm . H NMR (500 MHz, CDCl
like, J = 14.0, 7.2, H-6’a), 2.88 (1H, dd, J = 14.0, 2.1, H-6’b), 2.89 (1H, dd, J = 13.5, 6.3, H-5a), 3.01
1H, dd, J = 13.5, 6.3, H-5b), 3.45 (1H, ddd, J = 9.7, 7.2, 2.1, H-5’), 3.47 (1H, dd-like, J = 9.7, 9.2, H-
’), 3.50 (1H, dd, J = 9.2, 7.8, H-2’), 3.53 (1H, td, J = 6.3, 3.5, H-4), 3.56 (1H, dd, J = 8.3, 8.1, H-1a),
3.61 (1H, dd, J = 6.9, 3.5, H-3), 3.62 (1H, dd, J = 9.2, 9.2, H-3’), 3.70 (1H, dd, J = 8.3, 6.3, H-1b), 4.33
1H, ddd-like, J = 8.1, 6.9, 6.3, H-2), 4.43/4.63 (each 1H, d, J = 11.7, CH Ph), 4.49 (1H, d, J = 7.8, H-
’), 4.58/4.88 (each 1H, d, J = 10.9, CH Ph), 4.64/4.91(each 1H, d, J = 12.0, CH Ph), 4.68/4.81 (each
3
). IR (neat): 3032, 2873, 1496, 1454, 1365, 1250,
-1 1
1
3
) : 1.35/1.41 [each 3H, s, C(CH ], 2.67 (1H, dd-
3 2
)
(
4
(
2
1
2
2
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6
1H, d, J = 11.8, CH
Ph), 4.71/4.96 (each 1H, d, J = 10.9, CH
Ph), 4.77/4.93 (each 1H, d, J = 10.9,
) : 25.7/26.6 [C(CH ], 33.2 (C-5),
Ph), 76.0 (C-5’), 77.1 (C-2), 78.5 (C-4),
79.0 (C-3), 80.3 (C-4’), 82.4 (C-2’), 84.5 (C-3’), 102.3 (C-1’), 108.9 [C(CH ],
27.59/127.64/127.82/127.86/127.93/127.99/128.1/128.22/128.26/128.33/128.38/128.42/128.45/128.5
2
2
13
CH
2
Ph), 7.22–7.38 (30H, m, arom.). C-NMR (125 MHz, CDCl
3
3 2
)
34.3 (C-6’), 65.9 (C-1), 71.1/72.1/74.1/74.9/75.1/75.7 (CH
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3 2
)
1
5
+
(d, arom.), 137.1/137.8/137.9/138.3/138.4/138.5 (s, arom.). FABMS m/z: 933 [M+Na] .
Benzyl 2,3,4-Tri-O-benzyl-6-S-(3,4-di-O-benzyl-5-deoxy--D-xylitol-5-yl)-6-thio--D-
glucopyranoside (30). A mixture of 29 (2.83 g, 3.1 mmol), TFA (20 mL), chloroform (30 mL), and
water (30 mL) was vigorously stirred at room temperature for 4 h. The reaction mixture was poured
into cold water (200 mL) and extracted with CHCl
with aqueous NaHCO and brine, and condensed to give a colorless viscous oil (2.81 g), which on col-
umn chromatography (n-hexane-acetone, 10:1 → 3:1) gave title compound 30 (2.41 g, 89%) as a col-
3
(3×50 mL). The extract was successively washed
3
2
D
3
orless waxy solid. Mp. 82–83 °C. []
497, 1454, 1400, 1358, 1207, 1192, 1111, 1076, 1029 cm . H NMR (800 MHz, CDCl
dd, J = 6.4, 5.6, OH), 2.51 (1H, d, J = 5.6, OH), 2.78 (1H, dd, J = 14.4, 7.2, H-6’a), 2.945 (1H, dd, J =
3.6, 6.4, H-5a), 2.950 (1H, dd, J = 14.4, 2.4, H-6’b), 3.07 (1H, dd, J = 13.6, 5.6, H-5b), 3.50 (1H, ddd,
–1.15 (c = 2.05, CHCl
3
). IR (KBr): 3395, 3032, 2904, 2859,
-1 1
1
3
) : 2.11 (1H,
1
J = 9.6, 7.2, 2.4, H-5’), 3.51 (1H, dd, J = 8.8, 8.0, H-2’), 3.528 (1H, ddd-like, J = ca. 11.2, 6.4, 4.8, H-
1a), 3.534 (1H, dd-like, J = ca. 9.6, 8.8, H-4’), 3.55 (1H, ddd-like, J = ca. 11.2, 5.6, 5.2, H-1b), 3.63
(
1H, dd, J = 8.8, 8.8, H-3’), 3.69 (1H, dd, J = 5.0, 4.0, H-3), 3.82 (1H, ddd-like, J = ca. 5.6, 5.2, 4.8,
.0, H-2), 3.86 (1H, ddd-like, J = ca. 6.4, 5.6, 5.0, H-4), 4.50 (1H, d, J = 8.0, H-1’), 4.54/4.716 (each
4
1H, d, J = 11.2, CH Ph), 4.56/4.718 (each 1H, d, J = 11.2, CH Ph), 4.59/4.88 (each 1H, d, J = 10.4,
2
2
CH
2
Ph), 4.65/4.92 (each 1H, d, J = 12.0, CH
2
Ph), 4.74/4.95 (each 1H, d, J = 11.2, CH
2
Ph), 4.77/4.93
) : 33.9 (C-5),
2
Ph), 75.72 (C-5’), 79.1 (C-4),
1
3
(
2 3
each 1H, d, J = 10.4, CH Ph), 7.22–7.38 (30H, m, arom.). C-NMR (125 MHz, CDCl
34.3 (C-6’), 64.1 (C-1), 71.0 (C-2), 71.2/72.8/74.6/74.8/75.2/75.69 (CH
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7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
79.3 (C-3), 80.1 (C-4’), 82.3 (C-2’), 84.5 (C-3’), 102.4 (C-1’), 108.9 [C(CH
3
)
2
],
127.6/127.88/127.97/128.08/128.13/128.26/128.34/128.38/128.46/128.54
(d,
arom.),
+
1
37.1/137.7/137.8/138.0/138.3/138.4 (s, arom.). LRMS (FAB) m/z: 893 [M+Na] . HRMS (FAB) m/z:
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
[M+Na] Calcd for C53
H
58
O
9
SNa 893.3699; Found 893.3701.
Benzyl 2,3,4-Tri-O-benzyl-6-S-[3,4-di-O-benzyl-1-(tert-butyldiphenylsilyl)-5-deoxy--D-
xylitol-5-yl]-6-thio--D-glucopyranoside (31). A mixture of 30 (2.38 g, 2.74 mmol), tert-
butyldiphenylsilyl chloride (1.0 mL, 3.85 mmol), imidazole (550 mg, 8.09 mmol), and DMF (12 mL)
was stirred at room temperature for 3h. The reaction mixture was poured into cold water (200 mL) and
extracted with EtOAc (1×100 mL, 2×30 mL). The extract was washed with brine, and condensed to
give a colorless oil (3.53 g), which on column chromatography (n-hexane-EtOAc, 10:1 → 3:1) gave
2
5
title compound 31 (2.97 g, 98%) as a colorless viscous oil. []
557, 3032, 2932, 1497, 1454, 1392, 1361, 1211, 1111, 1069, 1030 cm . H NMR (800 MHz, CDCl
: 1.04 (9H, s,[C(CH ]), 2.42 (1H, d, J = 7.2, OH), 2.75 (1H, dd-like, J = ca. 13.6, 8.0, H-6’a), 2.94
1H, dd, J = 13.6, 6.4, H-5a), 2.98 (1H, dd, J = 13.6 1.6, H-6’b), 3.03 (1H, dd, J = 13.6, 4.8, H-5b),
.47 (1H, m, H-4’), 3.48 (1H, m, H-5’), 3.51 (1H, dd, J = 8.8, 8.0, H-2’), 3.61 (1H, dd, J = 10.4, 7.0,
H-1a), 3.62 (1H, dd, J = 8.8, 8.8, H-3’), 3.66 (1H, dd, J = 10.4, 6.4, H-1b), 3.83 (1H, ddd, J = 6.4, 4.8,
.8, H-4), 3.90 (1H, ddd-like, J = ca. 7.2, 7.0, 6.4, 3.2, H-2), 3.91 (1H, dd, J = 4.8, 3.2, H-3), 4.48 (1H,
d, J = 8.0, H-1’), 4.53/4.71 (each 1H, d, J = 11.2, CH Ph), 4.55/4.65 (each 1H, d, J = 11.2, CH Ph),
4.58/4.86 (each 1H, d, J = 11.2, CH Ph), 4.64/4.91 (each 1H, d, J = 12.0, CH Ph), 4.70/4.95 (each 1H,
d, J = 10.4, CH Ph), 4.76/4.92 (each 1H, d, J = 10.4, CH Ph), 7.21–7.64 (40H, m, arom.). C-NMR
125 MHz, CDCl ) : 19.2 [C(CH ], 26.9 [C(CH ], 34.2 (C-5), 34.6 (C-6’), 64.6 (C-1),
71.0/72.8/74.7/74.8/75.1/75.7 (CH Ph), 71.1 (C-2), 75.8 (C-5’), 77.9 (C-3), 79.5 (C-4), 80.4 (C-4’),
84.6 (C-3’), 102.3 (C-1’),
27.66/127.75/127.82/127.85/127.90/127.97/128.02/128.1/128.34/128.36/ 128.40/128.43/129.8/135.6
D
3
–1.07 (c = 0.95, CHCl ). IR (neat):
-1 1
3
3
)
3 3
)
(
3
4
2
2
2
2
1
3
2
2
(
3
3
)
3
3 3
)
2
82.4
(C-2’),
1
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2
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4
+
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(d, arom.), 133.2/133.2/137.2/138.0/138.1/138.4/138.5 (s, arom.). LRMS (FAB) m/z: 1131 [M+Na] .
+
HRMS (FAB) m/z: [M+Na] Calcd for C69
H
76
O
9
SSiNa 1131.4877; Found 1131.4878.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Benzyl 2,3,4-Tri-O-benzyl-6-S-[3,4-di-O-benzyl-1-(tert-butyldiphenylsilyl)-5-deoxy-2-
O-methanesulfonyl--D-xylitol-5-yl]-6-thio--D-glucopyranoside (12). To a mixture of 31
(
2.95 g, 2.66 mmol), triethylamine (2.4 mL, 17.3 mmol), trimethylamine hydrochloride (70 mg, 0.73
mmol), and CH Cl (30 mL) was added methanesulfonyl chloride (0.42 mL, 5.42 mmol) at 0 °C. After
2
2
being stirred at 0 °C for 30 min, the reaction mixture was poured into cold water (200 mL) and ex-
tracted with EtOAc (2×50 mL, 1×30 mL). The extract was washed with brine and condensed in vacuo
to give colorless oil (3.44 g), which on column chromatography (n-hexane-EtOAc, 10:1 → 3:1) gave
2
D
5
title compound 12 (2.90 g, 92%) as a colorless viscous oil. []
–24.7 (c = 0.74, CHCl
3
). IR (neat):
032, 2943, 2859, 1497, 1454, 1357, 1177, 1111, 1069, 1029 cm . H NMR (800 MHz, CDCl ) :
.04 (9H, s,[C(CH ]), 2.67 (1H, dd, J = 13.6, 8.0, H-6’a), 2.86 (3H, s, SO CH ), 2.89 (1H, dd, J =
-1 1
3
1
3
3
)
3
2
3
13.6, 2.4, H-6’b), 2.91 (1H, dd, J = 13.6, 8.0, H-5a), 3.08 (1H, dd, J = 13.6, 4.8, H-5b), 3.44 (1H, dd-
like, J = 9.6, 8.8, H-4’), 3.49 (1H, ddd-like, J = ca. 9.6, 8.0, 2.4, H-5’), 3.51 (1H, dd, J = 8.8, 8.0, H-
2
4
’), 3.64 (1H, dd, J = ca. 8.8, 8.8, H-3’), 3.66 (1H, dd, J = 12.8, 4.8, H-1a), 3.72 (1H, ddd, J = 8.0, 4.8,
.0, H-4), 3.94 (1H, dd, J = 12.8, 3.2, H-1b), 4.21 (1H, dd, J = 6.4, 4.0, H-3), 4.31/4.58 (each 1H, d, J
=
11.2, CH
H, d, J = 12.0, CH
CH Ph), 4.77/4.93 (each 1H, d, J = 10.4, CH
2
Ph), 4.51 (1H, d, J = 8.0, H-1’), 4.53/4.86 (each 1H, d, J = 10.4, CH
Ph), 4.67/4.69 (each 1H, d, J = 12.0, CH Ph), 4.72/4.95 (each 1H, d, J = 10.4,
Ph), 4.82 (1H, ddd, J = 6.4, 4.8, 3.2, H-2), 7.15–7.65
) : 19.2 [C(CH ], 26.9 [C(CH ], 32.3 (C-5), 34.2
), 63.2 (C-1), 71.2/71.8/74.8/75.15/75.16/75.7 (CH Ph), 76.5 (C-5’), 76.86 (C-3),
6.90 (C-4), 80.7 (C-4’), 82.4 (C-2’), 83.4 (C-2), 84.5 (C-3’), 102.5 (C-1’),
127.62/127.65/127.81/127.83/128.85/127.92/128.0/128.1/128.26/128.33/128.37/128.40/128.43/128.5/
29.88/129.92/135.5/135.6 (d, arom.), 132.6/132.9/137.2/ 137.4/137.6/138.0/138.4/138.5 (s, arom.).
2
Ph), 4.64/4.91 (each
1
2
2
2
2
1
3
(
(
40H, m, arom.). C-NMR (200 MHz, CDCl
3
3
)
3
3 3
)
C-6’), 38.2 (SO CH
2
3
2
7
1
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1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
+
LRMS (FAB) m/z: 1187 [M+H] . HRMS (FAB) m/z: [M+H] Calcd for C70
H
79
O
11
S
2
Si 1187.4833;
Found 1187.4828.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Cyclization of Mesylate (12). A solution of 12 (1.5 g, 1.26 mmol) in EtOH (30 mL) was heated
under reflux for 5 h. Removal of the solvent in vacuo left a colorless oil (1.53 g), which on column
3 3
chromatography, which on column chromatography (CHCl →CHCl -MeOH, 50:1 → 30:1 → 10:1)
gave 2,3-di-O-benzyl-5-O-(tert-butyldiphenylsilyl)-1,4-dideoxy-1,4-{(R)-[benzyl 6-deoxy-2,3,4-tri-O-
benzyl--D-grucopyranoside-6-yl]episulfoniumylidene}-D-arabinitol methanesulfonate (-32, 1.34 g,
8
9%) and a ca. 1:5 mixture of -32 and its -isomer -32 (82 mg, 5%).
25
D
Major isomer -32: colorless amorphous. []
3
+9.3 (c = 1.18, CHCl ). IR (neat): 3032, 2932,
-1 1
2886, 1497, 1454, 1427, 1396, 1361, 1203, 1068, 1037 cm . H NMR (800 MHz, CDCl ) : 1.02 (9H,
3
–
s,[C(CH
3
)
3
]), 2.74 (3H, s, OSO
2
CH
3
), 3.32 (1H, dd, J = 9.6, 8.0, H-2’), 3.42 (1H, dd, J = 9.6, 8.8, H-
4
’), 3.65 (1H, dd-like, J = 9.6, 8.8, H-3’), 3.74 (1H, dd, J = 13.6, 4.0, H-1a), 3.85 (1H, ddd, J = 9.6, 6.4,
4.0, H-5’), 3.86 (1H, dd, J = 11.2, 6.4, H-5a), 3.90 (1H, dd, J = 11.2, 6.4, H-5b), 3.92 (1H, dd, J = 13.6,
6
3
.4, H-6’a), 4.01 (1H, dd, J = 13.6, 4.8, H-1b), 4.11 (1H, td, J = 6.4, 3.2, H-4), 4.13 (1H, dd, J = 13.6,
.2, H-6’b), 4.22 (1H, dd-like, J = 4.0, 3.2, H-3), 4.46/4.57 (each 1H, d, J = 11.2, CH Ph), 4.48 (1H, d,
2
2 2
J = 8.0, H-1’), 4.49/4.61 (each 1H, d, J = 11.2, CH Ph), 4.55/4.71 (each 1H, d, J = 12.0, CH Ph),
4
.59/4.81 (each 1H, d, J = 11.2, CH
11.2, CH
MHz, CDCl
2
Ph), 4.68 (1H, ddd, J = 4.8, 4.0, 4.0, H-2), 4.75/4.86 (each 1H, d, J
13
=
2
Ph), 4.77/4.92 (each 1H, d, J = 10.4, CH
2
Ph), 7.16–7.55 (40H, m, arom.). C-NMR (200
–
3
) : 19.2 [C(CH
3
)
3
], 26.9 [C(CH
3
)
3
], 39.7 ( OSO
2
CH
Ph), 77.3 (C-4’), 81.8 (C-2’), 82.2 (C-2),
(C-3’), 102.9 (C-1’),
3
), 46.2 (C-1), 47.1 (C-6’), 60.9 (C-
5
8
1
), 66.9 (C-4), 71.1 (C-5’), 71.9/72.3/72.4/74.2/74.8/75.6 (CH
2
2.7
(C-3),
83.9
27.67/127.70/127.8/127.9/128.05/128.09/128.2/128.3/128.36/128.38/128.5/128.6/128.68/128.72/
129.0/130.29/130.33/135.4/135.5 (d, arom.), 131.9/132.0/136.3/136.5/136.9/137.6/138.1/138.2 (s,
+
–
+
arom.). LRMS (FAB) m/z: 1091 [M–CH
3
SO
3
] , 95 [CH
3
SO
3
] . HRMS (FAB) m/z: [M–CH
3
SO
3
]
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1
2
3
4
–
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Calcd for C69
4.9804.
H
O
SSi 1091.4952; Found 1091.4957, [CH
SO
] Calcd for CH
O
S 94.9803; Found
75
8
3
3
3
3
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
NMR data for minor isomer -32 extracted from the spectrum of a mixture (/ = ca. 1:5):
–
1.04 (9H, s,[C(CH
3
)
3
]), 2.74 (3H, s, OSO
2
CH
3
), 3.09 (1H, dd, J = 9.6, 8.8, H-4’), 3.13 (1H, dd, J =
1
2.8, 10.4, H-6’a), 3.37 (1H, dd, J = 9.6, 8.0 H-2’), 3.74 (1H, dd, J = 9.6, 8.8, H-3’), 3.86 (1H, dd-like,
J = 11.2, 7.2, H-5a), 3.90 (1H, dd-like, J = 11.2, 6.4, H-5b), 3.93 (1H, ddd-like, J = ca. 7.2, 6.4, 2.4, H-
), 4.06 (1H, dd, J = 12.8, 3.2, H-6’b), 4.09 (1H, ddd-like, J = ca. 10.4, 9.6, 3.2, H-5’), 4.12 (1H, dd, J
14.4, 4.8, H-1a), 4.18 (1H, br s-like, H-3), 4.30/4.35 (each 1H, d, J = 12.0, CH Ph), 4.416/4.46 (each
H, d, J = 12.0, CH Ph), 4.420/4.68 (each 1H, d, J = 11.2, CH Ph), 4.45 (1H, br d-like, J = 14.4, H-1b),
.68 (1H, m, H-2), 4.70/4.94 (each 1H, d, J = 10.4, CH Ph), 4.71/4.90 (each 1H, d, J = 10.4, CH Ph),
4
=
2
1
4
2
2
2
2
13
4.80/4.86 (each 1H, d, J = 12.0, CH
NMR (200 MHz, CDCl
2
Ph), 4.84 (1H, d, J = 8.0, H-1’), 7.06–7.59 (40H, m, arom.). C-
–
3
) : 19.1 [C(CH
3
)
3
], 26.8 [C(CH
)
3 3
], 39.7 ( OSO
2
CH
Ph), 79.9 (C-4’), 82.1 (C-2’),
82.7 (C-2), 83.7 (C-3’), 84.4 (C-3), 103.1 (C-1’), 127.62/127.68/127.69/127.7/127.87/127.93/
3
), 41.2 (C-6’), 46.2 (C-1),
5
9.9 (C-5), 62.9 (C-4), 69.1 (C-5’), 71.87/71.90/72.3/74.2/74.6/75.7 (CH
2
1
28.00/128.16/128.20/128.32/128.37/128.42/128.69/128.72/130.50/130.52/135.42/135.5 (d, arom.),
31.7/131.9/136.0/ 136.1/137.57/137.63/138.25/138.32 (s, arom.).
1
1
,4-Dideoxy-1,4-[(S)-(6-deoxy-1-D-glucopyranos-6-yl)episulfoniumylidene]-2,3,5-tri-O-
benzyl-D-arabinitol Methanesulfonate (33). A suspension of 10% Pd-C (800 mg) in a mixture of
0% aqueous TFA (25 mL) was pre-equilibrated with hydrogen. To the suspension was added a solu-
2
tion of a solution of -32 (820 mg, 0.69 mmol) in 1,4-dioxane (10 mL). The resulted mixture was hy-
drogenated at 55–60°C under atmospheric pressure until uptake of hydrogen ceased. The catalyst was
filtered off and washed with water. After the combined filtrate and the washings were condensed in
vacuo to give a colorless oil (290 mg), which was used for the subsequent reaction without further puri-
fication. For analytical purpose a small portion was purified by column chromatography
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1
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1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1
(CHCl
800 MHz, D
9.6, H-4’), 3.49 (0.5H, dd, J = 9.6, 9.6, H-4’), 3.55 (0.5H, dd, J = 9.6, 9.6, H-3’), 3.52 (0.5H, dd, J
9.6, 3.2, H-2’), 3.77 (0.5H, dd, J = 9.6, 9.6 Hz, H-3’), 3.88 (0.5H, dd, J = 13.6, 1.6, H-6’a), 3.89
0.5H, d-like, J = 13.6 H-6’a), 3.92–3.97 (1H, m, H-1a and H-1a), 3.96–3.99 (0.5H, m, H-5’),
.94–3.99 (1H, m, H-1b and H-1b), 3.99–4.02 (1H, m, H-5a and H-5a), 4.06/4.07 (each 0.5H, dd,
3
/CH
3
OH, 10/1→5/1→3/1) to give title compound 33 as a ca. 1:1 amoneric mixture. H-NMR
(
2
O) : 3.33 (0.5H, dd, J = 9.6, 8.0, H-2’), 3.39 (3H, s, CH SO ), 3.47 (0.5H. dd, J = 10.4,
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
=
(
3
J = 13.6, 3.2, H-1’b and H-1’b), 4.14–4.20 (2H, m, H-5b, H-5b, H-4 and H-4), 4.31 (0.5H, ddd,
J = 10.4, 8.8, 3.2, H-5’), 4.51 (1H, m, H-3 and H-3), 4.73 (0.5H, d, J =8.0, H-1’), 4.80 (1H, m, ,
1
3
H-2 and H-2), 5.31 (0.5H, d, J = 3.2, H-1’). C-NMR (200 MHz, D
49.6/49.9 (C-6’ and C6’), 50.9 (C-1 and C1), 61.9 (C-5 and C5), 70.3 (C-5’), 73.1/73.2 (C-
 and C4), 73.9 (C-2’), 74.2 (C-5’), 74.9 (C-4’), 74.98 (C-3’), 75.02 (C-4’), 76.6 (C-2’),
77.9 (C-3’), 79.8 (C-2 and C2), 80.3/80.4 (C-3 and C3), 95.0 (C-1’), 98.9 (C-1’). HRMS
2
O) : 41.1 (CH
3 3
SO ),
4
+
–
(
ESI) m/z: [M–CH
3
SO
3 21 8 3 3
] Calcd for C11H O S 313.0952; Found 313.0942; [CH SO ] Calcd for
9
4.9808, Found 94.9791.
1
,4-Dideoxy-1,4-[(S)-(6-deoxy-1-D-glucopyranos-6-yl)episulfoniumylidene]-2,3,5-tri-O-
–
benzyl-D-arabinitol Chloride (34). A mixture of 33 (240 mg), ion exchange resin IRA-400J (Cl
form, 5 g), methanol (10 mL), and water (2 mL) was stirred at room temperature for 12 h. The resin
was filtered off, and the filtrate was evaporated to give a pale yellow oil (203 mg), which was used for
the subsequent reaction without further purification. For analytical purpose a small portion was puri-
fied by column chromatography (CHCl
3
/CH
3
OH, 10/1→5/1→3/1) to give title compound 34 as a ca.
O) : 3.27 (0.5H, dd, J = 9.6, 8.0, H-2’), 3.42 (0.5H.
1
1
:1 amoneric mixture. H-NMR (800 MHz, D
2
dd, J = 10.4, 9.6, H-4’), 3.43 (0.5H, dd, J = 9.6, 9.6, H-4’), 3.50 (0.5H, dd, J = 9.6, 9.6, H-3’), 3.56
0.5H, dd, J = 9.6, 3.2, H-2’), 3.71 (0.5H, dd, J = 9.6, 9.6 Hz, H-3’), 3.832/3.834 (each 0.5H, dd, J
(
28
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The Journal of Organic Chemistry
1
2
3
4
5
=
13.6, 8.8, H-6’a and H-6’a), 3.87–3.91 (1H, m, H-1a and H-1a), 3.90–3.92 (0.5H, m, H-5’),
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
.90–3.95 (1H, m, H-1b and H-1b), 3.93–3.96 (1H, m, H-5a and H-5a), 4.01/4.02 (each 0.5H, dd,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
J = 13.6, 3.2, H-1’b and H-1’b), 4.09–4.15 (2H, m, H-5b, H-5b, H-4 and H-4), 4.25 (0.5H,
ddd, J = 10.4, 8.8, 3.2, H-5’), 4.45 (1H, m, H-3 and H-3), 4.68 (0.5H, d, J =8.0, H-1’), 4.75 (1H,
1
3
m, , H-2 and H-2), 5.26 (0.5H, d, J = 3.2, H-1’). C-NMR (200 MHz, D O) : 49.5/49.8 (C-6’
2
an d C6’), 50.9 (C-1 and C1), 61.82/61.83 (C-5 and C5), 70.3 (C-5’), 73.0/73.1 (C-4 and
C4), 73.9 (C-2’), 74.2 (C-5’), 74.8 (C-4’), 74.9 (C-3’), 75.0 (C-4’), 76.5 (C-2’), 77.8 (C-3’),
79.7 (C-2 and C2), 80.2/80.4 (C-3 and C3), 95.0 (C-1’), 98.8 (C-1’). HRMS (ESI) m/z: [M–
+
Cl] Calcd for C11
H
21
O
8
S 313.0952; Found 313.0944.
1
,4-Dideoxy-1,4-{(R)-[(2S,3S,4R,5S)-2,3,4,5,6-pentahydroxyhexyl]episulfoniumylidene}-
D-arabinitol Chloride (Neoponkoranol 6). To a solution of 34 (160 mg) in water (5 mL) was
added NaBH (60 mg, 1.57 mmol) at 0 °C, and the mixture was stirred at 0 °C for 5 h. The reaction
4
mixture was acidified with 1 M HCl to pH 4 at 0 °C. After the reaction mixture was condensed in vac-
uo, the residue was triturated with methanol. The MeOH insoluble material was filtered off, and
washed with methanol. The combined filtrate and washings were condensed in vacuo, to give a color-
3
less solid (208 mg), which on column chromatography (CHCl /MeOH = 5/1→3/1→3/2) gave as color-
less solid (172 mg). Re-purification by HPLC (H
2
O) gave title compound 6 (82 mg, 52% from -32)
1
13
6
as a colorless solid. H and C NMR data of 6 agreed well with those reported.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI:
1
13
H and C NMR spectra for all new compounds (PDF)
AUTHOR INFORMATION
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