Synthesis of α-2-deoxy-ulosides by Michael addition of hex-1-en-3-ones

Article abstract of DOI:10.1016/j.tet.2012.12.085

α-2-Deoxyulosides were synthesized in moderate to good yields by Michael addition of various O-nucleophiles to hex-1-en-3-ones in the presence of NaOH. These glycosyl additions were complete in 30 min at room temperature with high α-stereoselectivity in 5

Full text of DOI:10.1016/j.tet.2012.12.085

Tetrahedron 69 (2013) 2494e2500
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of
a
-2-deoxy-ulosides by Michael addition
of hex-1-en-3-ones
Zi-Ping Lin a, Fung Fuh Wong a, Yen-Bo Chen a, Yu-Cheng Lin a, Masayuki Kimura c,
,
Kimiyoshi Kaneko c, Hiroyuki Takayama c, Jin Bin Wu a, Chun-Hung Lin b
,
*
,
Hui-Chang Lin a
*
a Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Rd., Taichung 40402, Taiwan
b Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road, Section 2, Nan-Kang, Taipei 11529, Taiwan
c Department of Medico Pharmaceutical Science, Nihon Pharmaceutical University, 10281, Komuro, Inamachi, Kita-Adachigun, Saitama, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-2-Deoxyulosides were synthesized in moderate to good yields by Michael addition of various O-nu-
cleophiles to hex-1-en-3-ones in the presence of NaOH. These glycosyl additions were complete in
30 min at room temperature with high -stereoselectivity in 53e92% yield. In addition, high -stereo-
selectivity was also observed when S-nucleophiles were examined at 0 ꢀC for 90 min.
Received 2 November 2012
Received in revised form 13 December 2012
Accepted 21 December 2012
Available online 16 January 2013
a
a
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
Keywords:
2-Deoxyglycoside
Hex-1-en-3-one
a
-2-Deoxy-uloside
Michael addition
Sodium hydroxide
1. Introduction
2. Result and discussion
2-Deoxyglycosides are commonly found in many biologically
important natural products,1 such as anthracyclin antibiotics,2 aur-
eolic acids,3 avermectins,4 orthosomycins,5 cardiac glycosides,6 and
angucycline.7 2-Deoxyglycosides have been attractive targets for
synthetic chemists because of their indispensable roles in antibi-
otic,2,8 antitumor,9 and anti-inflammatory activities.10 Several
Hex-1-en-3-ones are versatile starting materials utilized for the
synthesis of pyrazoles,19 isoxazole,20 and -enamino ketone.21 Hex-
b
1-en-3-ones 1 and 2 that were prepared from fully protected endo-
glucals,22 first reacted with n-octanol under basic conditions. Sev-
eral Lewis bases (3.0 equiv) were examined (Table 1), including
sodium hydroxide (NaOH), 1,8-diazabicyclo[5.4.0]undec-7-ene
(DBU), potassium carbonate (K2CO3), potassium tert-butoxide
(t-BuOK), and 4-dimethylaminopyridine (DMAP). The reactions
were carried out in dichloromethane at room temperature for 0.5 h.
Among these reactions shown in entries iev of Table 1, NaOH was
methods have been developed to prepare a-2-deoxyulosides from
hex-1-en-3-one, including acid-mediated conjugation,11 base-
catalyzed Michael type reaction,12 rhodium(I)-catalyzed 1,4-
addition,13 enolate alkylation,14 palladium-catalyzed addition,15 and
organocopper addition.16,17 However, these reactions usually take
a long time and high temperature for completion. Recently our group
applied microwave-assisted glycosylation of hex-1-en-3-uloses to
found to provide the desired product n-octyl-2-deoxy-
ulosides (5) with the highest isolated yield (75%) and stereo-
selectivity (ratio of -anomers: 90/10). It is noted that the amount
a-deoxy-
a/b
synthesize
synthetic efforts, we present herein a new synthetic method pre-
paring -2-deoxyulosides by Michael additions of various alcohols to
a
-2-deoxyulosides with success.18 In continuation of our
of NaOH can be reduced to 1.0 equiv, but the reaction needs longer
time (2 h) for completion.
a
Meanwhile, a variety of solvents were examined, including
DMSO, DMF, THF,1,4-dioxane, CH2Cl2, toluene, and benzene (entries
viexi of Table 1). Interestingly the reactions in nonpolar solvent (e.g.,
benzene and toluene) were found to afford higher yields and ster-
eoselectivities, in contrast to those in polar solvent (e.g., DMSO and
DMF). As a result, the optimal condition is to carry out the reaction in
benzene in presence of NaOH (see entries xi in Table 1).
hex-1-en-3-ones. Particularly, several Lewis bases and solvents were
examined to obtain satisfying yields and stereoselectivity.
* Corresponding authors. Tel.: þ886 4 22053366x5612; fax: þ886 4 22078083
(H.-C.L.); tel.: þ886 2 27890110; fax: þ886 2 26514705 (C.-H.L.); e-mail addresses:
chunhung@gate.sinica.edu.tw (C.-H. Lin), lhc550005@yahoo.com.tw, huichang@
mail.cmu.edu.tw (H.-C. Lin).
0040-4020/$ e see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.12.085

Z.-P. Lin et al. / Tetrahedron 69 (2013) 2494e2500
2495
corresponding 13C NMR spectrum, such as the C3-carbonyl at
Table 1
Application of different Lewis base and solvent for synthesis of
a
-2-deoxy-ulosides
d
204.23, the anomeric carbon at d 98.51, and the 2-deoxy carbon at
5a
d
31.77. The IR absorption spectrum of 5 exhibited a major peak at
1734 cmꢁ1, in agreement with the stretching bond of the C3-
carbonyl group.
OBn
O
OBn
Lewis base
O
BnO
BnO
+
n-Octanol
O
solvent
O
To expand the synthetic utility, sugar alcohols 12e14 were
employed as the acceptor substrates. Under the aforementioned
condition (i.e., a benzene solution of hex-1-en-3-one 1 or 2 treated
with each of 12e14 in the presence of 3.0 equiv of NaOH at room
temperature), disaccharide products 15e18 were obtained in
53e62% yields (Table 3). In comparison with the previous exam-
O
rt
4
30 min
1
5
Entry
Base (3 equiv)
Solvent
5 (Yield,
a
/
b)
1 (Residual)
i
ii
DBU
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DMSO
DMF
THF
1,4-Dioxane
Toluene
Benzene
(46%, 73/27)
6%b
32%
53%
0%
12%
86%
76%
56%
85%
36%
9%
K2CO3
t-BuOK
NaOH
DMAP
NaOH
NaOH
NaOH
NaOH
NaOH
NaOH
ples, high
a-selectivity (the ratios of a/b 2-deoxyulosides >91/9)
iii
iv
v
vi
vii
viii
ix
x
0%
was observed, indicating that bulkier or sterically hindered alcohols
(75%, 90/10)
0%
appear to favor a-selectivity, likely due to the anomeric effect. All of
15%b
the product structures were confirmed by 1H and 13C NMR, DEPT,
32%b
COSY, and other spectroscopic methods.
5%b
32%b
(83%, 86/14)
(89%, 90/10)
Table 3
xi
0%
Application of different sugar alcohols for synthesis of disaccharides 15e18a
a
OR1
O
OR1
O
All reactions were carried out at room temperature with n-octanol in the
NaOH
presence of Lewis bases (3.0 equiv).
R1O
R1O
+
ROH
b
The a-anomer is predominant with a/b
ratio of 3/1e5/1 on the basis of 1H NMR
O
benzene
rt
30 min
O
OR
15-18
integration.
1 R1 = Bn
2 R1 = PMB
Furthermore, several alkyl alcohols were examined for the re-
action with 4,6-di-O-benzyl hex-1-en-3-one 1 at room temperature
for 0.5 h, including methanol, n-hexanol, n-octanol, benzyl alcohol,
isopropanol, and cyclohexanol (entries ievi in Table 2, re-
spectively). 2-Deoxyulosides 3e8 were obtained in 75e92% yields
b
Entry
i
Donor
Acceptor (ROH)
Products (yield, a/b)
OH
O
O
12
O
1
15 (61%, 96/4)
O
O
with high a-stereoselectivity (ratio of a/b-anomers: 85/15e94/6).
Similar results were observed when the protecting group of 1 was
substituted with p-methoxybenzyl ether. Under the same condi-
tion, the reactions of 2 gave products 9e11 in 73e89% yields with
OH
O
MeO
MeO
13
ii
1
1
2
16 (53%, 92/8)
17 (53%, 91/9)
18 (62%, 94/6)
satisfying stereoselectivity (ratio of
a/b-anomers: 89/11e92/8)
MeO
OMe
(entries viieix in Table 2, respectively).
OH
O
Table 2
BnO
BnO
iii
14
Application of different alcohols for synthesis of a
-2-deoxy-ulosidesa
BnO
OMe
OR1
O
OR1
O
NaOH
OH
O
R1O
R1O
+
ROH
MeO
MeO
O
benzene
rt
30 min
iv
O
13
OR
3-11
MeO
OMe
1 R1 = Bn
2 R1 = PMB
a
All reactions were carried out at room temperature in benzene with sugar
nucleophiles in the presence of NaOH (3.0 equiv).
The a/b
ratios were determined by 1H NMR.
b
b
Entry
Donor
Acceptor (ROH)
Products (yield, a/b)
When 1-butanethiol was examined for Michael addition of hex-
1-en-3-one 1, lowstereoselectivity was found (ratio of -anomers:
72/28, entry i in Table 4) at room temperature. The -selectivity was
significantly improved once the reactions were carried out at 0 ꢀC
(ratio of -anomers: 92/8, entry ii in Table 4). The observation was
applicable to other thiols (such as n-octanethiol and -toluenethiol,
see entries iiieiv) and p-methoxybenzylated hex-1-en-3-one (2, see
entries vevii). These reactions were carried out at 0 ꢀC for 90 min to
generate S-2-deoxy-ulosides 19e24 in 90e93% yields. In addition,
there was no reaction except for the formation of disulfide com-
pound 2623 when sugar thiol 25 was examined (entry viii).
i
ii
1
1
1
1
1
1
2
2
2
Methanol
n-Hexanol
n-Octanol
Benzyl alcohol
Isopropanol
Cyclohexanol
Methanol
3 (92%, 87/13)
4 (89%, 85/15)
5 (89%, 90/10)
6 (86%, 88/12)
7 (78%, 94/6)
8 (75%, 90/10)
9 (89%, 89/11)
10 (85%, 92/8)
11 (73%, 91/9)
a/b
iii
iv
v
vi
vii
viii
ix
a
a/b
a
n-Octanol
Cyclohexanol
a
All reactions were carried out at room temperature in benzene with alcohol-
nucleophiles in the presence of NaOH (3.0 equiv).
b
The a/b
ratios were determined by 1H NMR.
1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) or potassium cya-
nide/18-crown-6 were previously utilized for Michael-type re-
actions of O-nucleophiles (or S-nucleophiles), but low yields (20%e
45%) were obtained.12 These reactions also required longer reaction
time and higher temperature. In contrast, a new method was
developed for preparation of 2-deoxyglycosides with satisfying
The configuration/stereochemistry of the 1,4-addition products
were carefully examined by 1H and 13C NMR, DEPT and other
spectroscopic methods. For instance, 2-deoxyulosides 5 was di-
agnosed in accordance with the 1H NMR spectrum, including the
new anomeric proton at
(J2a,1¼4.4 Hz, J2a,2b¼14.0 Hz), and H2 equatorial at
d
5.13 (J1,2a¼4.4 Hz), H2 axial at
d
2.70
2.52
d
a-stereoselectivity, which is applicable for both O- and S-
(J2b,2a¼14.0 Hz). There are characteristic signals in the
nucleophiles.

2496
Z.-P. Lin et al. / Tetrahedron 69 (2013) 2494e2500
Table 4
shown by the abbreviations, such as s (singlet), d (doublet), t (triplet),
q (quartet), and m (multiplet). Elemental analyses were carried out
Application of different thiols for synthesis of a
-2-deoxy-ulosides 19e24a
OR1
O
OR1
on a Heraeus CHNeO RAPID element analyzer.
O
NaOH
R1O
R1O
+
RSH
3.2. Typical procedure of Michael additions for preparing 2-
deoxy-ulosides derivatives 3e11
O
benzene
O
SR
19-24
0 oC
1 R1 = Bn
2 R1 = PMB
90 min
Hex-1-en-3-one (e.g., 1 or 2, 1.0 equiv) was mixed with alcohol
substrate (3.0 equiv) and NaOH (3.0 equiv) in benzene at room
temperature for 0.5 h. When the reaction was completed, the
resulting solution was added to CH2Cl2 (50 mL), washed with H2O
(20 mLꢂ2), and brine (20 mLꢂ2). The organic layer was concen-
trated under reduced pressure and purified by column chroma-
tography on silica gel (35% EtOAc in hexanes as eluant) to give the
desired product (e.g., 3e11) in 73e92% yield.
c
Entry
Donor
Acceptor (RSH)
Products (yield, a/b)
i
ii
1
1
1
1
2
2
2
1-Butanethiol
1-Butanethiol
1-Octanethiol
-Toluenethiol
1-Butanethiol
1-Octanethiol
19 (83%, 72/28)b
19 (93%, 92/8)
20 (91%, 92/8)
21 (92%, 94/6)
22 (90%, 93/7)
23 (93%, 94/6)
24 (91%, 92/8)
iii
iv
v
vi
vii
a
a
-Toluenethiol
3.2.1. 1-Methyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (3). Pale yellow oil; IR (CHCl3) 2929, 1730, 1643,
1114 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.27e7.18 (10H, m, ArH),
a-D-erythro-hexopyr-
SH
S
O
O
BnO
BnO
;
d
BnO
viii
1
BnO
5.04 (1H, d, J1,2a¼4.0 Hz, H1), 4.82 (1H, d, J¼11.2 Hz, CH2Ph), 4.53
(1H, d, J¼12.0 Hz, CH2Ph), 4.43 (1H, d, J¼12.0 Hz, CH2Ph), 4.34 (1H, d,
J¼11.2 Hz, CH2Ph), 4.00 (1H, d, J4,5¼9.6 Hz, H4), 3.94e3.91 (1H, m,
H5), 3.71 (1H, dd, J6a,5¼3.6 Hz, J6a,6b¼10.8 Hz, H6a), 3.65 (1H, dd,
J6b,5¼2.0 Hz, J6b,6a¼10.8 Hz, H6b), 3.25 (3H, s, OCH3), 2.70 (1H, dd,
J2a,1¼4.0 Hz, J2a,2b¼14.0 Hz, H2a), 2.52 (1H, d, J2b,2a¼14.0 Hz, H2b);
BnO
BnO
26 (95%)b
OMe
OMe
2
25
a
All reactions were carried out at 0 ꢀC in benzene with 3.0 equiv of thiol-
nucleophiles in the presence of NaOH (3.0 equiv).
b
The reaction was carried out at room temperature in benzene with 3.0 equiv of
thiol-nucleophiles in the presence of NaOH (3.0 equiv).
13C NMR (CDCl3, 100 MHz)
d 203.92, 137.88, 137.48, 128.38, 128.37,
The a/b
ratios were determined by 1H NMR.
c
128.33, 128.32, 128.21, 128.20, 127.87, 127.83, 127.82, 127.73, 99.69,
78.98, 73.59, 73.47, 72.35, 68.52, 54.78, 46.62; LRMS (EI) m/z (rel
intens) 356 (Mþ, 1), 129 (10), 97 (24), 91 (100); HRMS (EI) m/z calcd
for C21H24O5 (Mþ) 356.1624, found 356.1624. Anal. Calcd for
C21H24O5; C: 70.77; H: 6.79. Found: C: 70.72; H: 6.83.
In conclusion, hex-1-en-3-ones were successfully converted to
-2-deoxy-ulosides by reacting with various O- and S-nucleophiles
in the presence of NaOH via Michael addition. In comparison with
previous procedures, this new developed method led to excellent
yields and great a-stereoselectivity.
a
3.2.2. 1-Hexyl-2-deoxy-4,6-di-O-benzyl-
3-ulose (4). Pale yellow oil; IR (CHCl3) 2950, 1725, 1635, 1100 cmꢁ1
1H NMR (CDCl3, 400 MHz)
7.31e7.23 (10H, m, ArH), 5.18 (1H, d,
a-D-erythro-hexopyranosid-
;
d
3. Experimental section
3.1. General procedure
J1,2a¼4.4 Hz, H1), 4.88 (1H, d, J¼11.2 Hz, CH2Ph), 4.58 (1H, d,
J¼12.0 Hz, CH2Ph), 4.48 (1H, d, J¼12.0 Hz, CH2Ph), 4.40 (1H, d,
J¼11.2 Hz, CH2Ph), 4.15 (1H, dd, J4,2a¼0.8 HZ, J4,5¼10.0 Hz, H4), 4.01
(1H, ddd, J5,6b¼2.0 Hz, J5,6a¼3.6 Hz, J5,4¼10.0 Hz, H5), 3.76 (1H, dd,
J6a,5¼3.6 Hz, J6a,6b¼10.4 Hz, H6a), 3.69 (1H, dd, J6b,5¼2.0 Hz,
J6b,6a¼10.4 Hz, H6b), 3.62e3.56 (1H, m, H1a0), 3.36e3.32 (1H, m,
H1b0), 2.75 (1H, ddd, J2a,4¼0.8 Hz, J2a,1¼4.4 Hz, J2a,2b¼14.0 Hz, H2a),
2.57 (1H, d, J2b,2a¼14.0 Hz, H2b), 1.53e1.46 (2H, m, H20), 1.29e1.18
All purchased chemicals were of reagent grade. All reactions were
carried out under a nitrogen atmosphere and monitored by TLC
analysis (layer thickness: 250
carried out with silica gel 60 (70e230 mesh for gravity column, or
230e400 mesh for flash column). Commercially available reagents
were directly used without further purification unless otherwise
noted. Dichloromethane, ethyl acetate, hexanes, and methanol
were purchased from Mallinckrodt Chemical Co. The following
compounds were purchased from Acros Chemical Co:
benzyl alcohol, methanol, n-hexanol, n-octanol, benzylthiol,
mm). Column chromatography was
(6H, m, H30eH50), 0.84 (3H, t, J6 ,5 ¼7.2 Hz, H6 ); 13C NMR (CDCl3,
0
0
0
100 MHz)
d 204.13, 137.92, 137.49, 128.37, 128.36, 128.34, 128.33,
128.24, 128.23, 127.88, 127.83, 127.82, 127.72, 98.53, 79.11, 73.59,
73.53, 72.29, 68.57, 67.78, 46.74, 31.54, 29.21, 25.74, 22.50, 13.98;
LRMS (EI) m/z (rel intens) 426 (Mþ, 1), 199 (26), 97 (21), 91 (100);
HRMS (EI) m/z calcd for C26H34O5 (Mþ) 426.2406, found 426.2409.
Anal. Calcd for C26H34O5; C: 73.21; H: 8.03. Found: C: 73.24; H: 8.07.
isopropanol, cyclohexanol, n-butylthiol, n-octylthiol,
a-toluenethiol,
tri-O-acetyl- -glucal, sodium hydroxide, 1,8-diazabicyclo[5.4.0]
D
undec-7-ene, potassium carbonate, potassium tert-butoxide, 4-
dimethylaminopyridine, N,N-dimethylformamide, dimethylsulf-
oxide, 1,4-dioxane, tetrahydrofuran, dichloromethane, benzene, tol-
3.2.3. 1-Octyl-2-deoxy-4,6-di-O-benzyl-
3-ulose (5). Pale yellow oil; IR (CHCl3) 2927, 1732, 1635, 1114 cmꢁ1
1H NMR (CDCl3, 400 MHz)
7.26e7.17 (10H, m, ArH), 5.13 (1H, d,
a-D-erythro-hexopyranosid-
;
d
uene, iodomethane, benzyl bromide, 1,2:3,4-di-O-isopropylidene-
a
-
J1,2a¼4.4 Hz, H1), 4.82 (1H, d, J¼10.8 Hz, CH2Ph), 4.53 (1H, d,
J¼12.0 Hz, CH2Ph), 4.42 (1H, d, J¼12.0 Hz, CH2Ph), 4.33 (1H, d,
J¼10.8 Hz, CH2Ph), 4.11 (1H, d, J4,5¼10.0 Hz, H4), 3.96e3.93 (1H, m,
H5), 3.71 (1H, dd, J6a,5¼3.2 Hz, J6a,6b¼10.4 Hz, H6a), 3.63 (1H, dd,
J6b,5¼2.0 Hz, J6b,6a¼10.4 Hz, H6b), 3.56e3.50 (1H, m, H1a0),
3.31e3.25 (1H, m, H1b0), 2.73e2.68 (1H, m, H2a), 2.52 (1H, d,
J2b,2a¼14.0 Hz, H2b), 1.45e1.40 (2H, 0m, H20), 1.22e1.16 (10H, m,
D
-galactopyranoside, and methyl- -glucopyranoside. Silica gel
a-D
column chromatography was carried out by using Merck Reagents
Silica Ge 60 (particle size 0.063e0.200 mm, 70e230 mesh ASTM).
Infrared (IR) spectra were measured on a Bomem Michelson Series
FT-IR spectrometer. The wavenumbers reported are referenced to the
polystyrene 1601 cmꢁ1 absorption. Absorption intensities are
recorded by the following abbreviations: s, strong; m, medium; w,
weak. 1H NMR spectra were recorded at a Bruker spectrometer (200
or 400 MHz) with CDCl3 (dH 7.24) and DMSO-d6 (dH 2.50) as the in-
ternal standard; 13C NMR spectra were recorded at 50 or 100 MHz
with CDCl3 [dC 77.0 (central line of a triplet)]. Splitting patterns are
H30eH70), 0.79 (3H, t, J8 ,7 ¼7.2 Hz, H8 ); 13C NMR (CDCl3, 100 MHz)
0
0
d
204.23, 137.81, 137.40, 128.37, 128.36, 128.34, 128.33, 128.25,
128.24, 127.90, 127.86, 127.85, 127.73, 98.51, 79.03, 73.55, 73.54,
72.18, 68.39, 67.74, 46.71, 31.77, 29.30, 29.22, 29.15, 26.06, 22.61,
14.08; LRMS (EI) m/z (rel intens) 454 (Mþ, 1), 227 (46), 91 (100);

Z.-P. Lin et al. / Tetrahedron 69 (2013) 2494e2500
2497
HRMS (EI) m/z calcd for C28H38O5 (Mþ) 454.2719, found 454.2730.
H2b); 13C NMR (CDCl3, 100 MHz)
d
204.05, 159.37, 159.28, 129.93,
Anal. Calcd for C28H38O5; C: 73.98; H: 8.43. Found: C: 74.02; H: 8.46.
129.83, 129.82, 129.61, 129.49, 129.48, 113.76, 113.75, 113.70, 113.69,
99.67, 78.60, 73.16, 73.06, 72.31, 68.04, 55.20, 55.19, 54.74, 46.59;
LRMS (FAB) m/z (rel intens) 439 (Mþþ23, 6.3),176 (20),154 (41),136
(39), 121 (100), 55 (32); HRMS (FAB) m/z calcd for C23H28O7Na
(Mþþ23) 439.1733, found 439.1734. Anal. Calcd for C23H28O7; C:
66.33; H: 6.78. Found: C: 66.38; H: 6.84.
3.2.4. Benzyl-2-deoxy-4,6-di-O-benzyl-
3-ulose (6). Pale yellow oil; IR (CHCl3) 2928, 1722, 1641, 1110 cmꢁ1
1H NMR (CDCl3, 400 MHz)
7.27e7.17 (15H, m, ArH), 5.22 (1H, d,
a-D-erythro-hexopyranosid-
;
d
J1,2a¼4.4 Hz, H1), 4.82 (1H, d, J¼11.2 Hz, CH2Ph), 4.58 (1H, d,
J¼12.0 Hz, CH2Ph), 4.53 (1H, d, J¼12.0 Hz, CH2Ph), 4.43 (1H, d,
J¼12.0 Hz, CH2Ph), 4.41 (1H, d, J¼12.0 Hz, CH2Ph), 4.34 (1H, d,
J¼11.2 Hz, CH2Ph), 4.12 (1H, d, J4,5¼9.6 Hz, H4), 4.00 (1H, ddd,
J5,6a¼2.0 Hz, J5,6b¼3.2 Hz, J5,4¼9.6 Hz, H5), 3.69 (1H, dd, J6a,5¼3.2 Hz,
J6a,6b¼10.8 Hz, H6a), 3.60 (1H, dd, J6b,5¼2.0 Hz, J6b,6a¼10.8 Hz, H6b),
2.71 (1H, dd, J2a,1¼4.4 Hz, J2a,2b¼14.0 Hz, H2a), 2.56 (1H, d,
3.2.8. 1-Octyl-2-deoxy-4,6-di-O-p-methoxybenzyl-
opyranosid-3-ulose (10). Pale yellow oil; IR (CHCl3) 2925, 1727,
1638, 1109 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.19e7.11 (4H, m,
a-D-erythro-hex-
;
d
ArH), 6.80e6.75 (4H, m, ArH), 5.12 (1H, d, J1,2a¼4.0 Hz, H1), 4.73
(1H, d, J¼10.8 Hz, CH2Ph), 4.49 (1H, d, J¼11.6 Hz, CH2Ph), 4.36 (1H, d,
J¼11.6 Hz, CH2Ph), 4.27 (1H, d, J¼10.8 Hz, CH2Ph), 4.06 (1H, d,
J4,5¼9.6 Hz, H4), 3.93e3.91 (1H, m, H5), 3.72 (3H, s, OCH3), 3.71 (3H,
s, OCH3), 3.67 (1H, dd, J6a,5¼3.2 Hz, J6a,6b¼10.8 Hz, H6a), 3.59 (1H,
dd, J6b,5¼1.6 Hz, J6b,6a¼10.8 Hz, H6b), 3.56e3.50 (1H, m, H1a0),
3.31e3.26 (1H, m, H1b0), 2.69 (1H, dd, J2a,1¼4.0 Hz, J2a,2b¼14.0 Hz,
H2a), 2.51 (1H, d, J2b,2a¼14.0 Hz, H2b), 1.43e1.42 (2H, m, H20),
1.18e1.17 (10H, m, H30eH70), 0.80 (3H, t, J¼6.4, H80); 13C NMR
J2b,2a¼14.0 Hz, H2b); 13C NMR (CDCl3, 100 MHz)
d 203.87, 137.87,
137.42, 136.81, 128.37, 128.36, 128.35, 128.34, 128.31, 128.30, 128.20,
128.19, 127.84, 127.83, 127.82, 127.80, 127.79, 127.78, 127.70, 97.71,
79.03, 73.56, 73.50, 72.60, 68.98, 68.44, 46.52; LRMS (EI) m/z (rel
intens) 432 (Mþ, 1), 97 (23), 91 (100); HRMS (EI) m/z calcd for
C27H28O5 (Mþ) 432.1937, found 432.1941. Anal. Calcd for C27H28O5;
C: 74.98; H: 6.53. Found: C: 75.02; H: 6.56.
(CDCl3, 100 MHz)
d 204.27, 159.40, 159.39, 130.01, 129.87, 129.86,
3.2.5. Isopropyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (7). Pale yellow oil; IR (CHCl3) 2924, 1729, 1631,
1096 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.29e7.18 (10H, m, ArH),
a
-
D
-erythro-hexopyr-
129.64, 129.50, 129.49, 113.76, 113.75, 113.73, 113.72, 98.52, 78.74,
73.17, 73.16, 72.26, 68.08, 67.74, 55.21, 55.20, 46.72, 31.77, 29.30,
29.24, 29.14, 26.07, 22.60, 14.04; LRMS (FAB) m/z (rel intens) 537
(Mþþ23, 1.2), 149 (20), 121 (100), 69 (58), 55 (88); HRMS (FAB) m/z
calcd for C30H42O7Na (Mþþ23) 537.2828, found 537.2832. Anal.
Calcd for C30H42O7; C: 70.01; H: 8.23. Found: C: 70.06; H: 8.28.
;
d
5.27 (1H, d, J1,2a¼4.4 Hz, H1), 4.83 (1H, d, J¼11.2 Hz, CH2Ph), 4.54
(1H, d, J¼12.0 Hz, CH2Ph), 4.43 (1H, d, J¼12.0 Hz, CH2Ph), 4.35 (1H, d,
J¼11.2 Hz, CH2Ph), 4.12 (1H, d, J4,5¼9.6 Hz, H4), 4.04e4.01 (1H, m,
H5), 3.85e3.79 (1H, m, H10), 3.72 (1H, dd, J6a,5¼3.2 Hz,
J6a,6b¼10.4 Hz, H6a), 3.63 (1H, J6b,6a¼10.4 Hz, H6b), 2.72 (1H, dd,
J2a,1¼4.4 Hz, J2a,2b¼14.0 Hz, H2a), 2.47 (1H, d, J2b,2a¼14.0 Hz, H2b),
1.07 (3H, d, J¼6.4 Hz, CH3), 1.04 (3H, d, J¼6.0 Hz, CH3); 13C NMR
3.2.9. 1-Cyclohexyl-2-deoxy-4,6-di-O-p-methoxybenzyl-
hexopyranosid-3-ulose (11). Pale yellow oil; IR (CHCl3) 2927, 1726,
1628, 1111 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.18e7.11 (4H, m,
a-D-erythro-
;
d
(CDCl3, 100 MHz)
d
204.31, 137.92, 137.49, 128.38, 128.37, 128.35,
ArH), 6.80e6.75 (4H, m, ArH), 5.31 (1H, d, J1,2a¼4.0 Hz, H1), 4.73
(1H, d, J¼10.8 Hz, CH2Ph), 4.49 (1H, d, J¼11.6 Hz, CH2Ph), 4.35 (1H, d,
J¼11.6 Hz, CH2Ph), 4.27 (1H, d, J¼10.8 Hz, CH2Ph), 4.07 (1H, d,
J4,5¼9.6 Hz, H4), 4.03e4.01 (1H, m, H5), 3.72 (3H, s, OCH3), 3.71 (3H,
s, OCH3), 3.68 (1H, dd, J6a,5¼3.2 Hz, J6a,6b¼10.8 Hz, H6a), 3.58 (1H,
J6b,5¼1.2 Hz, J6b,6a¼10.8 Hz, H6b), 3.52e3.47 (1H, m, H10), 2.71 (1H,
dd, J2a,1¼4.0 Hz, J2a,2b¼14.0 Hz, H2a), 2.47 (1H, d, J2b,2a¼14.0 Hz,
H2b), 1.72e1.13 (10H, m, H20eH60); 13C NMR (CDCl3, 100 MHz)
128.34, 128.27, 128.26, 127.90, 127.84, 127.83, 127.72, 96.51, 79.18,
73.56, 73.55, 72.43, 69.19, 68.52, 47.15, 23.06, 21.17; LRMS (EI) m/z
(rel intens) 384 (Mþ, 1), 205 (8), 97 (23), 91 (100); HRMS (EI) m/z
calcd for C23H28O5 (Mþ) 384.1937, found 384.1939. Anal. Calcd for
C23H28O5; C: 71.85; H: 7.34. Found: C: 71.92; H: 7.35.
3.2.6. 1-Cyclohexyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (8). Yellow solid; mp 53e54 ꢀC; IR (CHCl3) 2931,
1724, 1643, 1109 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
7.27e7.18 (10H,
a-D-erythro-hexopyr-
d
204.48, 159.39, 159.38, 130.01, 129.88, 129.87, 129.66, 129.49,
d
129.48, 113.75, 113.74, 113.73, 113.72, 96.37, 78.85, 74.95, 73.15,
73.14, 72.39, 68.10, 55.22, 55.21, 47.15, 33.09, 31.14, 25.52, 23.99,
23.73; LRMS (FAB) m/z (rel intens) 507 (Mþþ23, 7), 107 (32), 121
(100), 136 (59), 154 (63), 219 (7); HRMS (FAB) m/z calcd for
C28H36O7Na (Mþþ23) 507.2359, found 507.2368. Anal. Calcd for
C28H36O7; C: 69.40; H: 7.49. Found: C: 69.47; H: 7.51.
m, ArH), 5.32 (1H, d, J1,2a¼4.4 Hz, H1), 4.83 (1H, d, J¼11.2 Hz, CH2Ph),
4.54 (1H, d, J¼12.0 Hz, CH2Ph), 4.43 (1H, d, J¼12.0 Hz, CH2Ph), 4.35
(1H, d, J¼11.2 Hz, CH2Ph), 4.11 (1H, d, J4,5¼9.6 Hz, H4), 4.07e4.04
(1H, m, H5), 3.72 (1H, dd, J6a,5¼3.2 Hz, J6a,6b¼10.8 Hz, H6a), 3.64
(1H, J6b,5¼1.2 Hz, J6b,6a¼10.8 Hz, H6b), 3.53e3.48 (1H, m, H10), 2.72
(1H, dd, J2a,1¼4.4 Hz, J2a,2b¼14.0 Hz, H2a), 2.48 (1H, d, J2b,2a¼14.0 Hz,
H2b), 1.73e1.12 (10H, m, H20eH60); 13C NMR (CDCl3, 100 MHz)
3.3. Typical procedure of Michael addition for preparing
d
204.35, 137.94, 137.49, 128.35, 128.34, 128.33, 128.32, 128.25,
2-deoxy-ulosides derivatives 15e18
128.24, 127.88, 127.81, 127.80, 127.70, 96.39, 79.22, 75.03, 73.56,
73.55, 72.40, 68.58, 47.17, 33.11, 31.16, 25.52, 24.00, 23.75; LRMS
(FAB) m/z (rel intens) 447 (Mþþ23, 3.6),154 (22), 105 (44), 91 (100);
HRMS (FAB) m/z calcd for C26H32O5Na (Mþþ23) 447.2147, found
447.2148. Anal. Calcd for C26H32O5; C: 73.56; H: 7.60. Found: C:
73.61; H: 7.65.
Hex-1-en-3-one (e.g., 1 and 2, 1.0 equiv) was mixed with
sugar alcohol substrate (e.g., 12e14, 3.0 equiv) and NaOH
(3.0 equiv) in benzene at room temperature for 0.5 h. When the
reaction was completed, the resulting solution was added to
CH2Cl2 (50 mL), washed with H2O (20 mLꢂ2), and brine
(20 mLꢂ2). The organic layer was concentrated under reduced
pressure and purified by column chromatography on silica gel
(70% EtOAc in hexanes as eluant) to give the desired product
(e.g., 15e18) in 53e62% yield.
3.2.7. 1-Methyl-2-deoxy-4,6-di-O-p-methoxybenzyl-
hexopyranosid-3-ulose (9). Pale yellow oil; IR (CHCl3) 2932, 1730,
1635, 1093 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.18e7.11 (4H, m,
a-D-erythro-
;
d
ArH), 6.80e6.74 (4H, m, ArH), 5.03 (1H, d, J1,2a¼4.0 Hz, H1), 4.73
(1H, d, J¼10.8 Hz, CH2Ph), 4.49 (1H, d, J¼11.6 Hz, CH2Ph), 4.37 (1H, d,
J¼11.6 Hz, CH2Ph), 4.26 (1H, d, J¼10.8 Hz, CH2Ph), 4.06 (1H, d,
J4,5¼9.6 Hz, H4), 3.90e3.88 (1H, m, H5), 3.71 (3H, s, OCH3), 3.70 (3H,
s, OCH3), 3.66 (1H, dd, J6a,5¼3.2 Hz, J6a,6b¼10.8 Hz, H6a), 3.60 (1H,
dd, J6b,5¼1.6 Hz, J6b,6a¼10.8 Hz, H6b), 3.24 (3H, s, OCH3), 2.70 (1H,
dd, J2a,1¼4.0 Hz, J2a,2b¼14.0 Hz, H2a), 2.51 (1H, d, J2b,2a¼14.0 Hz,
3.3.1. 2-Deoxy-4,6-di-O-benzyl-
ulose-(1/6)-1,2:3,4-di-O-isopropylidene-
(15). Pale yellow oil; IR (CHCl3) 2935, 1725, 1640, 1107 cmꢁ1
NMR (CDCl3, 400 MHz) 7.29e7.19 (10H, m, ArH), 5.39 (1H, d,
a
-
D
-erythro-hexopyranosid-3-
-galactopyranose
1H
D
;
d
0
0
0
J1 ,2 ¼4.8 Hz, H1 ), 5.22 (1H, d, J1,2a¼4.0 Hz, H1), 4.81 (1H, d,
J¼11.2 Hz, CH2Ph), 4.55 (1H, d, J¼12.0 Hz, CH2Ph), 4.51 (1H, br s,

2498
Z.-P. Lin et al. / Tetrahedron 69 (2013) 2494e2500
H30), 4.43 (1H, d, J¼12.0 Hz, CH2Ph), 4.36 (1H, d, J¼11.2 Hz, CH2Ph),
4.21e4.20 (1H, m, H20), 4.17e4.13 (2H, m, H4, H40), 4.01 (1H, br s,
H5), 3.82 (1H, br s, H50), 3.73 (1H, dd, J6a,5¼2.0 Hz, J6a,6b¼10.4 Hz,
NMR (CDCl3, 500 MHz) d 7.18e7.11 (4H, m, ArH), 6.80e6.75 (4H, m,
ArH), 5.24 (1H, d, J1,2a¼4.0 Hz, H1), 4.72 (1H, d, J¼11.0 Hz, CH2Ph),
0
0
0
4.65 (1H, d, J1 ,2 ¼3.5 Hz, H1 ), 4.49 (1H, d, J¼11.5 Hz, CH2Ph), 4.36
(1H, d, J¼11.5 Hz, CH2Ph), 4.27 (1H, d, J¼11.0 Hz, CH2Ph), 4.07 (1H, d,
J4,5¼10.0 Hz, H4), 4.01e3.98 (1H, m, H5), 3.74e3.71 (7H, m, H6a0,
OCH3), 3.67 (1H, dd, J6a,5¼3.0 Hz, J6a,6b¼10.5 Hz, H6a), 3.60 (1H, dd,
0
0
H6a), 3.67 (1H, d, J6b,6a¼10.4 Hz, H6b), 3.64 (1H, d, J6 a,5 ¼3.6 Hz,
H60a), 3.60e3.55 (1H, m, H60b), 2.71 (1H, dd, J2a,1¼4.0 Hz,
J2a,2b¼14.0 Hz, H2a), 2.57 (1H, d, J2b,2a¼14.0 Hz, H2b), 1.41 (3H, s,
CH3), 1.34 (3H, s, CH3), 1.25 (3H, s, CH3), 1.23 (3H, s, CH3); 13C NMR
0
0
J6b,5¼1.5 Hz, J6a,6b¼010.5 Hz, H6b), 3.55 (1H, dd, J6b ,5 ¼1.5 Hz,
0
0
0
(CDCl3, 100 MHz)
d
204.20, 137.89, 137.50, 128.38, 128.37, 128.33,
J6b ,6a ¼11.0 Hz, H6b ), 3.52 (3H, s, OCH3), 3.50e3.47 (1H, m, H5 ),
128.32, 128.20, 128.19, 127.86, 127.85, 127.72, 127.71, 109.19, 108.63,
98.87, 96.22, 79.03, 73.58, 73.50, 72.47, 70.62, 70.61, 70.50, 68.33,
65.85, 65.72, 46.53, 26.09, 25.96, 24.86, 24.50; LRMS (FAB) m/z (rel
intens) 607 (Mþþ23, 2.94), 55 (100), 69 (67), 91 (70), 105 (34), 159
(9); HRMS (FAB) m/z calcd for C32H40O10Na (Mþþ23) 607.2519,
found 607.2521. Anal. Calcd for C32H40O10; C: 65.74; H: 6.90. Found:
C: 65.77; H: 6.94.
3.42 (3H, s, OCH3), 3.40e3.37 (4H, m, H30, OCH3), 03.27 (3H, s, OCH3),
0
0
0
0
3.06 (1H, dd, J2 ,1 ¼3.5 Hz, J2 ,3 ¼9.5 Hz, H2 ), 2.98 (1H, dd,
J4 ,3 ¼9.0 Hz, J4 ,5 ¼10.0 Hz, H40), 2.69 (1H, dd, J2a,1¼4.0 Hz,
0
0
0
0
J2a,2b¼14.0 Hz, H2a), 2.55 (1H, d, J2b,2a¼14.0 Hz, H2b); 13C NMR
(CDCl3, 125 MHz)
d 203.97, 159.38, 159.31, 129.96, 129.82, 129.81,
129.69, 129.52, 129.51, 113.79, 113.78, 113.71, 113.70, 98.91, 97.22,
83.64, 81.80, 79.30, 78.61, 73.17, 73.06, 72.44, 69.72, 68.04, 65.82,
60.76, 60.51, 58.94, 55.24, 55.23, 55.10, 46.49; LRMS (FAB) m/z (rel
intens) 643 (Mþþ23, 16.6), 121 (100), 91 (89), 107 (47), 137 (62), 154
(66); HRMS (FAB) m/z calcd for C32H44O12Na (Mþþ23) 643.2730,
found 643.2738. Anal. Calcd for C32H44O12; C: 61.92; H: 7.15. Found:
C: 61.96; H: 7.19.
3.3.2. 2-Deoxy-4,6-di-O-benzyl-
(1/6)-1,2,3,4-tetra-O-methyl-
oil; IR (CHCl3) 2925, 1725, 1643, 1102 cmꢁ1
500 MHz)
a
-
D
-erythro-hexopyranosid-3-ulose-
-glucopyranose (16). Pale yellow
1H NMR (CDCl3,
7.27e7.19 (10H, m, ArH), 5.25 (1H, d, J1,2a¼4.0 Hz, H1),
a-D
;
d
0
0
0
4.83 (1H, d, J¼11.0 Hz, CH2Ph), 4.65 (1H, d, J1 ,2 ¼3.5 Hz, H1 ), 4.53
(1H, d, J¼12.0 Hz, CH2Ph), 4.44 (1H, d, J¼12.0 Hz, CH2Ph), 4.35 (1H, d,
J¼11.0 Hz, CH2Ph), 4.11 (1H, d, J4,5¼10.0 Hz, H4), 4.04e4.02 (1H, m,
H5), 3.73e3.69 (2H, m, H6a, H6a0), 3.65 (1H, dd, J6b,5¼1.5 Hz,
J6b,6a¼10.5 Hz, H6b), 3.58e3.55 (1H, m, H6b0), 3.53 (3H, s, OCH3),
3.51e3.48 (1H, m, H50), 3.42e3.37 (7H, m, H40, OCH3), 3.27 (3H, s,
3.4. Standard procedure of Michael addition for preparation
a-S-2-deoxy-ulosides derivatives 19e24
To a solution of hex-1-en-3-one 1 (1.0 equiv) in CH2Cl2 was
added with NaOH (3.0 equiv) and various alkylthiol (3.0 equiv). The
reaction mixture was stirred at 0 ꢀC for 1.5 h. When the reaction
was completed, the resulting solution was added to CH2Cl2 (50 mL),
washed with H2O (20 mLꢂ2), and brine (20 mLꢂ2). The organic
layer was concentrated under reduced pressure and purified by
column chromatography on silica gel (35% EtOAc in hexanes as
0
0
0
0
0
OCH3), 3.06 (1H, dd, J2 ,1 ¼3.5 Hz, J2 ,3 ¼9.5 Hz, H2 ), 2.99 (1H, dd,
J3 ,4 ¼9.0 Hz, J3 ,2 ¼9.5 Hz, H30), 2.70 (1H, dd, J2a,1¼4.0 Hz,
0
0
0
0
J2a,2b¼14.0 Hz, H2a), 2.57 (1H, d, J2b,2a¼14.0 Hz, H2b); 13C NMR
(CDCl3, 125 MHz)
d 203.84, 137.89, 137.55, 128.40, 128.39, 128.33,
128.32, 128.17, 128.16, 127.87, 127.83, 127.82, 127.75, 98.88, 97.24,
83.65, 81.81, 79.31, 78.97, 73.57, 73.45, 72.45, 69.72, 68.50, 65.84,
60.76, 60.50, 58.95, 55.11, 46.50; LRMS (FAB) m/z (rel intens) 583
(Mþþ23, 3.98), 91 (100), 55 (10), 75 (12), 101 (18), 181 (11); HRMS
(FAB) m/z calcd for C30H40O10Na (Mþþ23) 583.2519, found
583.2510. Anal. Calcd for C30H40O10; C: 64.27; H: 7.19. Found: C:
64.31; H: 7.23.
eluant) to give a-S-2-deoxy-ulosides 19e24 in 90e93% yields.
3.4.1. 1-S-Butyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (19). Pale yellow oil; IR (CHCl3) 2957, 1730, 1642,
1110 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.24e7.17 (10H, m, ArH),
a-D-erythro-hexopyr-
;
d
5.55 (1H, d, J1,2a¼6.8 Hz, H1), 4.82 (1H, d, J¼11.2 Hz, CH2Ph), 4.53
(1H, d, J¼12.0 Hz, CH2Ph), 4.41 (1H, d, J¼12.0 Hz, CH2Ph), 4.37e4.33
(1H, m, H5, CH2Ph), 4.08 (1H, d, J4,5¼9.6 Hz, H4), 3.74 (1H, dd,
J6a,5¼3.6 Hz, J6a,6b¼10.4 Hz, H6a), 3.62 (1H, dd, J6b,5¼1.6 Hz,
J6b,6a¼10.4 Hz, H6b), 3.02 (1H, dd, J2a,1¼6.8 Hz, J2a,2b¼14.4 Hz, H2a),
2.55e2.48 (2H, m, H2b, H10a), 2.43e2.36 (1H, m, H10b), 1.53e1.44
(2H, m, H20), 1.31e1.26 (2H, m, H30), 0.80 (3H, t, J¼7.2 Hz, H40); 13C
3.3.3. 2-Deoxy-4,6-di-O-benzyl-
(1/6)-2,3,4-tri-O-benzyl-1-O-methyl-
yellow oil; IR (CHCl3) 2928, 1731, 1643, 1100 cmꢁ1; 1H NMR (CDCl3,
400 MHz)
a
-
D-erythro-hexopyranosid-3-ulose-
a-D
-glucopyranose (17). Pale
d
7.29e7.13 (25H, m, ArH), 5.19 (1H, d, J1,2a¼4.0 Hz, H1),
4.88 (1H, d, J¼10.8 Hz, CH2Ph), 4.82 (1H, d, J¼10.8 Hz, CH2Ph), 4.81
(1H, d, J¼10.8 Hz, CH2Ph), 4.70 (1H, d, J¼10.8 Hz, CH2Ph), 4.68 (1H, d,
J¼12.0 Hz, CH2Ph), 4.56 (1H, d, J¼12.0 Hz, CH2Ph), 4.46 (1H, d,
NMR (CDCl3, 100 MHz)
d 203.44, 137.82, 137.42, 128.34, 128.33,
128.30, 128.29, 128.18, 128.17, 127.86, 127.77, 127.76, 127.70, 80.79,
79.12, 73.53, 73.47, 72.56, 68.58, 46.25, 31.28, 30.15, 21.90, 13.53;
LRMS (FAB) m/z (rel intens) 415 (Mþþ1, 1), 91 (100), 69 (54), 55
(72); HRMS (FAB) m/z calcd for C24H31O4S (Mþþ1) 415.1943, found
415.1940. Anal. Calcd for C24H30O4S; C: 69.53; H: 7.29. Found: C:
69.58; H: 7.33.
0
0
0
J¼12.0 Hz, CH2Ph), 4.65 (1H, d, J1 ,2 ¼3.6 Hz, H1 ), 4.42 (1H, d,
J¼11.2 Hz, CH2Ph), 4.34 (1H, d, J¼12.0 Hz, CH2Ph), 4.30 (1H, d,
J¼11.2 Hz, CH2Ph), 4.08 (1H, d, J¼10.0 Hz, H4), 3.90e3.86 (2H, m, H5,
H30), 3.71e3.61 (2H, m, H40, H6b), 3.55e3.46 (3H, m, H50, H60),
3.42e3.35 (2H, m, H20, H6a), 3.25 (3H, s, OCH3), 4.11 (1H, d,
J4,5¼10.0 Hz, H4), 4.04e4.02 (1H, m, H5), 3.73e3.69 (2H, m, H6a,
H6a0), 2.67 (1H, dd, J2a,1¼4.0 Hz, J2a,2b¼14.0 Hz, H2a), 2.54 (1H, d,
3.4.2. 1-S-Octyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (20). Pale yellow oil; IR (CHCl3) 2925, 1731, 1630,
1106 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.27e7.18 (10H, m, ArH),
a-D-erythro-hexopyr-
J2b,2a¼14.0 Hz, H2b); 13C NMR (CDCl3, 100 MHz)
d 203.85, 138.68,
138.30, 138.12, 137.85, 137.59, 128.43, 128.42, 128.41, 128.34, 128.33,
128.32, 128.28, 128.27, 128.26, 128.14, 128.13, 128.05, 128.04, 127.85,
127.84, 127.83, 127.82, 127.81, 127.80, 127.70, 127.51, 127.45, 127.44,
127.43, 127.42, 98.94, 97.90, 82.13, 80.00, 78.96, 77.59, 75.60, 74.80,
73.49, 73.43, 73.31, 72.39, 69.71, 68.29, 65.86, 55.13, 46.45; LRMS
(FAB) m/z (rel intens) 811 (Mþþ23, 1.82), 91 (100), 77 (26), 92 (41),
154 (9), 181 (31); HRMS (FAB) m/z calcd for C48H52O10Na (Mþþ23)
811.3458, found 811.3465. Anal. Calcd for C48H52O10; C: 73.08; H:
6.64. Found: C: 73.11; H: 6.69.
;
d
5.56 (1H, d, J1,2a¼7.2 Hz, H1), 4.83 (1H, d, J¼10.8 Hz, CH2Ph), 4.53
(1H, d, J¼12.0 Hz, CH2Ph), 4.42 (1H, d, J¼12.0 Hz, CH2Ph), 4.38e4.34
(2H, m, H5, CH2Ph), 4.35 (1H, d, J¼11.2 Hz, CH2Ph), 4.09 (1H, dd,
J4,2a¼0.8 Hz, J4,5¼10.4 Hz, H4), 3.74 (1H, dd, J6a,5¼3.6 Hz,
J6a,6b¼10.8 Hz, H6a), 3.62 (1H, dd, J6b,5¼2.0 Hz, J6b,6a¼10.8 Hz, H6b),
3.03 (1H, ddd, J2a,4¼0.8 Hz, J2a,1¼7.2 Hz, J2a,2b¼14.4 Hz, H2a),
2.54e2.36 (3H, m, H2b, H10), 1.53e1.46 (2H, m, H20), 1.27e1.17 (10H,
m, H30eH70), 0.80 (3H, t, J¼7.2 Hz, H80); 13C NMR (CDCl3, 100 MHz)
d
203.47, 137.87, 137.48, 128.37, 128.36, 128.34, 128.33, 128.22,
3.3.4. 2-Deoxy-4,6-di-O-p-methoxybenzyl-
anosid-3-ulose-(1/6)-1,2,3,4-tetra-O-methyl-
(18). Pale yellow oil; IR (CHCl3) 2945, 1737, 1644, 1105 cmꢁ1
a
-
D
-erythro-hexopyr-
-glucopyranose
1H
128.21, 127.90, 127.80, 127.79, 127.74, 80.86, 79.18, 73.59, 73.51,
72.60, 68.64, 46.30, 31.77, 30.55, 29.28, 29.12, 29.09, 28.87; LRMS
(EI) m/z (rel intens) 470 (Mþ, 1), 139 (11), 91 (100); HRMS (FAB) m/z
a-D
;

Z.-P. Lin et al. / Tetrahedron 69 (2013) 2494e2500
2499
calcd for C28H38O4S (Mþ) 470.2491, found 470.2481. Anal. Calcd for
C28H38O4S; C: 71.45; H: 8.14. Found: C: 71.49; H: 8.18.
J6b,5¼2.0 Hz, J6b,6a¼10.8 Hz, H6b), 2.95 (1H, ddd, J2a,4¼0.8 Hz,
J2a,1¼7.2 Hz, J2a,2b¼14.4 Hz, H2a), 2.42 (1H, d, J2b,2a¼14.4 Hz, H2b); 13
C
NMR (CDCl3, 100 MHz)
d 203.48, 159.39, 159.29, 137.49, 129.92,
3.4.3. 1-S-Benzyl-2-deoxy-4,6-di-O-benzyl-
anosid-3-ulose (21). Pale yellow oil; IR (CHCl3) 2923, 1730, 1631,
1115 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.25e7.16 (15H, m, ArH),
a
-
D
-erythro-hexopyr-
129.83,129.82,129.54,129.44,129.43,128.94,128.93,128.43,128.42,
127.03, 113.76, 113.75, 113.71, 113.70, 79.74, 78.77, 73.14, 73.10, 72.74,
68.02, 55.20, 55.19, 45.73, 34.34; LRMS (FAB) m/z (rel intens) 531
(Mþþ23, 3.0), 149 (100), 57 (90), 71 (76), 121 (83), 167 (52); HRMS
(FAB) m/z calcd for C29H32O6SNa (Mþþ23) 531.1817, found 531.1813.
Anal. Calcd for C29H32O6S; C: 68.48; H: 6.34. Found: C: 68.54; H: 6.38.
;
d
5.38 (1H, d, J1,2a¼7.2 Hz, H1), 4.81 (1H, d, J¼11.2 Hz, CH2Ph), 4.51
(1H, d, J¼12.0 Hz, CH2Ph), 4.42 (1H, d, J¼12.0 Hz, CH2Ph), 4.34 (1H, d,
J¼11.2 Hz, CH2Ph), 4.32 (1H, ddd, J5,6a¼2.0 Hz, J5,6b¼3.6 Hz,
J5,4¼9.6 Hz, H5), 4.06 (1H, d, J4,5¼9.6 Hz, H4), 3.67 (1H, dd,
J6a,5¼3.6 Hz, J6a,6b¼10.8 Hz, H6a), 3.64 (1H, d, J¼13.6 Hz, CH2Ph),
3.53 (1H, d, J¼13.6 Hz, CH2Ph), 3.48 (1H, dd, J6b,5¼2.0 Hz,
J6b,6a¼10.8 Hz, H6b), 2.96 (1H, dd, J2a,1¼7.2 Hz, J2a,2b¼14.8 Hz, H2a),
2.42 (1H, d, J2b,2a¼14.8 Hz, H2b); 13C NMR (CDCl3, 100 MHz)
3.4.7. Disulfide compound 25. Pale yellow oil; 1H NMR (CDCl3,
500 MHz)
d
7.27e7.15 (30H, m, ArH), 4.89 (2H, d, Ja,b¼11.0 Hz,
CH2Ph), 4.80 (2H, d, Ja,b¼11.0 Hz, CH2Ph), 4.71 (2H, d, Ja,b¼11.0 Hz,
CH2Ph), 4.67 (2H, d, Ja,b¼12.0 Hz, CH2Ph), 4.54 (2H, d, Ja,b¼12.0 Hz,
CH2Ph), 4.50 (2H, d, Ja,b¼11.0 Hz, CH2Ph), 4.47 (2H, d, J1,2¼3.5 Hz,
H1), 3.88 (2H, dd, J3,4¼9.0 Hz, J3,2¼9.5 Hz, H3), 3.79e3.75 (2H, m,
H5), 3.41 (2H, dd, J2,1¼3.5 Hz, J2,3¼9.5 Hz, H2), 3.29 (6H, s, OCH3),
3.22 (2H, dd, J4,3¼9.0 Hz, J4,5¼9.5 Hz, H4), 3.06 (2H, dd, J6a,5¼2.5 Hz,
J6a,6b¼13.5 Hz, H6a), 2.67 (2H, dd, J6b,5¼8.5 Hz, J6b,6a¼13.5 Hz, H6b);
d
203.35, 137.87, 137.50, 137.41, 128.96, 128.95, 128.46, 128.45,
128.38, 128.37, 128.33, 128.32, 128.20, 128.19, 127.89, 127.78, 127.77,
127.73, 127.06, 79.78, 79.13, 73.54, 72.75, 68.46, 45.76, 34.39; LRMS
(EI) m/z (rel intens) 448 (Mþ, 1), 97 (31), 91 (100); HRMS (FAB) m/z
calcd for C27H28O4S (Mþ) 448.1708, found 448.1713. Anal. Calcd for
C27H28O4S; C: 72.29; H: 6.29. Found: C: 72.34; H: 6.32.
13C NMR (CDCl3, 125 MHz)
d 138.60, 138.04, 138.03, 128.44, 128.43,
128.41, 128.40, 128.38, 128.37, 128.06, 128.05, 127.96, 127.95, 127.91,
127.77, 127.76, 127.75, 127.62, 97.79, 81.89, 80.65, 80.05, 75.73,
74.99, 73.30, 69.05, 55.27, 42.12.
3.4.4. 1-S-Butyl-2-deoxy-4,6-di-O-p-methoxybenzyl-
hexopyranosid-3-ulose (22). Pale yellow oil; IR (CHCl3) 2927, 1730,
1635, 1092 cmꢁ1 1H NMR (CDCl3, 400 MHz)
7.18e7.11 (4H, m,
a-D-erythro-
;
d
ArH), 6.79e6.74 (4H, m, ArH), 5.54 (1H, d, J1,2a¼5.6 Hz, H1), 4.72
(1H, d, J¼8.4 Hz, CH2Ph), 4.48 (1H, d, J¼9.6 Hz, CH2Ph), 4.34 (1H, d,
J¼9.6 Hz, CH2Ph), 4.32 (1H, br s, H5), 4.26 (1H, d, J¼8.4 Hz, CH2Ph),
4.05 (1H, d, J4,5¼8.0 Hz, H4), 3.74e3.68 (7H, m, H6a, OCH3), 3.56
(1H, dd, J6b,5¼1.2 Hz, J6b,6a¼8.4 Hz, H6b), 3.01 (1H, dd, J2a,1¼5.6 Hz,
J2a,2b¼11.6 Hz, H2a), 2.53e2.48 (2H, m, H2b, H10a), 2.42e2.36 (1H,
m, H10b), 1.51e1.43 (2H, m, H20), 1.32e1.24 (2H, m, H30), 0.80 (3H, t,
Acknowledgements
We thank National Science Council of Taiwan (NSC100-2113-M-
039-001-MY2) and China Medical University, Taiwan (CMU98-S-
15) for financial support.
J¼6.0 Hz, CH3); 13C NMR (CDCl3, 100 MHz)
d 203.64, 159.39, 159.29,
References and notes
129.86, 129.85, 129.58, 129.57, 129.50, 129.49, 113.76, 113.75, 113.72,
113.71, 80.80, 78.76, 73.16, 73.11, 72.55, 68.09, 55.22, 55.21, 46.26,
31.29, 30.15, 21.92, 13.55; LRMS (FAB) m/z (rel intens) 497 (Mþþ23,
4), 121 (100), 91 (29), 77 (25); HRMS (FAB) m/z calcd for
C26H34O6SNa (Mþþ23) 497.1974, found 497.1976. Anal. Calcd for
C26H34O6S; C: 65.80; H: 7.22. Found: C: 65.83; H: 7.25.
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7.18e7.11
a-D-erythro-
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d
(4H, m, ArH), 6.79e6.73 (4H, m, ArH), 5.53 (1H, d, J1,2a¼7.2 Hz, H1),
4.71 (1H, d, J¼10.8 Hz, CH2Ph), 4.48 (1H, d, J¼12.0 Hz, CH2Ph),
4.34e4.31 (2H, m, H5, CH2Ph), 4.26 (1H, d, J¼10.8 Hz, CH2Ph), 4.04
(1H, d, J4,5¼9.6 Hz, H4), 3.70e3.67 (7H, m, H6a, OCH3), 3.56 (1H, dd,
J6b,5¼1.6 Hz, J6b,6a¼10.8 Hz, H6b), 3.01 (1H, dd, J2a,1¼7.6 Hz,
J2a,2b¼14.8 Hz, H2a), 2.53e2.46 (2H, m, H2b, H10a), 2.41e2.34 (1H,
m, H10b), 1.53e1.44 (2H, m, H20), 1.26e1.17 (10H, m, H30eH70), 0.79
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(3H, t, J¼6.8 Hz, H80); 13C NMR (CDCl3, 100 MHz)
d 203.53, 159.34,
159.23, 129.85, 129.78, 129.77, 129.54, 129.40, 129.39, 113.69, 113.68,
113.66, 113.65, 80.77, 78.72, 73.09, 73.03, 72.52, 68.07, 55.13, 55.12,
46.20, 31.69, 30.45, 29.20, 29.05, 29.02, 28.78, 22.53, 13.98; LRMS
(FAB) m/z (rel intens) 553 (Mþþ23, 3.5), 121 (100), 57 (69), 122 (49),
149 (70), 154 (25); HRMS (FAB) m/z calcd for C30H42O6SNa (Mþþ23)
553.2600, found 553.2598. Anal. Calcd for C30H42O6S; C: 67.89; H:
7.98. Found: C: 67.94; H: 8.05.
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3.4.6. 1-S-
ythro-hexopyranosid-3-ulose (24). Pale yellow oil; IR (CHCl3) 2918,
1736,1631,1108 cmꢁ1; 1H NMR (CDCl3, 400 MHz)
7.20e7.11 (9H, m,
a-Toluenyl-2-deoxy-4,6-di-O-p-methoxybenzyl-a-D-er-
d
ArH), 6.80e6.74 (4H, m, ArH), 5.37 (1H, d, J1,2a¼7.2 Hz, H1), 4.71 (1H,
d, J¼10.8 Hz, CH2Ph), 4.47 (1H, d, J¼11.6 Hz, CH2Ph), 4.36 (1H, d,
J¼11.6 Hz, CH2Ph), 4.31e4.25 (2H, m, H5, CH2Ph), 4.03 (1H, d,
J4,5¼10.0 Hz, H4), 3.71 (3H, s, OMe), 3.70 (3H, s, OMe), 3.66e3.62 (2H,
m, H6a, CH2Ph), 3.53 (1H, d, J¼13.6 Hz, CH2Ph), 3.45 (1H, dd,

2500
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