High diastereoselective vinylogous Mannich reaction induced by O-pivaloylated d-galactosylamine as the chiral auxiliary: Stereoselective synthesis of 8-arylazocan-2-one

Article abstract of DOI:10.1016/j.carres.2013.03.020

The diastereospecific formation of β-N-glycosidically linked α,β-unsaturated δ-amino aldehyde derivatives has been achieved with high yield via a vinylogous Mannich reaction. The reaction was performed by using a O-pivaloylated galactosyl amine as a chiral template and AlCl ₃ as a promoter in THF. (S)-8-(p-Nitrophenyl) azocan-2-one can be stereoselective synthesized from (S) ethyl 7-galactosylamino-7-(p-nitrophenyl) hepta-2,4-dienoate by sequential hydrogenation of the double bond, cyclic lactam formation, and removal of the N-glycosidic auxiliary under basic conditions.

Full text of DOI:10.1016/j.carres.2013.03.020

Carbohydrate Research 374 (2013) 1–7
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
High diastereoselective vinylogous Mannich reaction induced
by O-pivaloylated D-galactosylamine as the chiral auxiliary:
stereoselective synthesis of 8-arylazocan-2-one
⇑
Bing Cui, Gang Hou, Yan Cai, Zhiwei Miao
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The diastereospecific formation of b-N-glycosidically linked
a,b-unsaturated d-amino aldehyde deriva-
Received 27 December 2012
Received in revised form 13 March 2013
Accepted 22 March 2013
tives has been achieved with high yield via a vinylogous Mannich reaction. The reaction was performed
by using a O-pivaloylated galactosyl amine as a chiral template and AlCl3 as a promoter in THF. (S)-8-(p-
Nitrophenyl) azocan-2-one can be stereoselective synthesized from (S) ethyl 7-galactosylamino-7-(p-
nitrophenyl)hepta-2,4-dienoate by sequential hydrogenation of the double bond, cyclic lactam formation,
and removal of the N-glycosidic auxiliary under basic conditions.
Available online 30 March 2013
Keywords:
Vinylogous Mannich reaction
Carbohydrate
Ó 2013 Elsevier Ltd. All rights reserved.
Chiral auxiliary
Stereoselective synthesis
8-Arylazocan-2-one
1. Introduction
dines.6 The groups of Kawe˛cki7 and Waldmann8 independently
developed the chiral auxiliaries to achieve good enantioselectivi-
Vinylogous carbon–carbon bond-forming reactions of dieno-
lates to imines are very important transformations in organic syn-
thesis and deliver highly functionalized products of great utility.1
Asymmetric vinylogous Mannich reactions furnishing d-amino-
ties of this reaction.
Carbohydrates have emerged as versatile auxiliaries and
reagents in regio- and stereoselective syntheses of many chiral
natural products and drugs.9 Among all the carbohydrates,
a
,b-unsaturated carbonyl compounds have been widely studied
O-acylglycosylamines, in particular the 2,3,4,6-tetra-O-pivaloyl-D-
in the context of the total synthesis of natural products.2 Consider-
ing the synthetic potential, the development of chiral nonracemic
galactopyranosylamine, proved to be effective chiral templates in
Strecker,10 Mannich,11 and Ugi reactions.12 Recently, our group re-
ported the diastereospecific formation of b-N-glycosidically linked
d-amino-a,b-unsaturated carbonyl building blocks is still challeng-
ing. However, in contrast to the much more developed methodol-
ogies for the addition of imines with cyclic silyl dienol ethers,3 the
asymmetric vinylogous Mannich reaction of acyclic silyl dienolates
has been little explored. In 2008, Schneider described the first
asymmetric vinylogous Mannich reaction of an acyclic silyl dieno-
late with imines that was catalyzed by a binol-based phosphoric
acid catalyst with high asymmetric induction.4 Subsequently, Car-
retero and co-workers successfully developed a copper(I) complex
of Fesulphos ligand as catalyst that could be applied both to silyl-
oxy furans as well as acyclic silyl dienolates as nucleophiles in
vinylogous Mannich reactions.5 Several chiral auxiliaries have also
been used to achieve good enantioselectivity of this reaction. Yang
described the use of bulky chiral benzylamines in the vinylogous
Mannich reaction with silylketene acetal mediated by Sn(OTf)2
leading to enantiomerically enriched piperidinones and 2-piperi-
a,b-unsaturated d-amino carbonyl derivatives via vinylogous Man-
nich reaction, utilizing O-pivaloyl-D-galactopyranosylamine as the
chiral auxiliary.13 Herein we report the chiral auxiliary asymmetric
vinylogous Mannich reaction of aldimines with silyl dienalate un-
der mild-conditions to afford the corresponding adducts in moder-
ate to good diastereomeric excesses and high yields and their
subsequent transformation.
2. Results and discussion
The synthesis of b-N-glycosidically linked d-amino-
rated aldehyde derivatives 5 started with the reaction of O-piva-
loyl- -galactosyl aldimines 3 and silyl dienolate 4. In order to
prepare the corresponding O-pivaloyl-
-galactosyl aldimines 3,14
2,3,4,6-tetra-O-pivaloyl-b- -galactopyranosylamine 1 was reacted
a,b-unsatu-
D
D
D
with aldehydes in the presence of acetic acid in 2-propanol. The
reactions proceeded smoothly in a short time at room temperature
under extremely mild conditions to afford desired products 3.15
⇑
Corresponding author.
E-mail address: miaozhiwei@nankai.edu.cn (Z. Miao).
0008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.03.020

2
B. Cui et al. / Carbohydrate Research 374 (2013) 1–7
Table 1
Survey of the conditions for the formation of 5ba
CHO
OPiv
O
PivO
PivO
H
N
4'
2'
2b
OPiv
PivO
OPiv
NO2
PivO
OTMS
5'
OPiv
1'
3'
4
O
O
O
NO2
NH2
N
PivO
PivO
Lewis acid
solvent
OPiv
OPiv
i-PrOH
1
5b
3b
NO2
Entry
Lewis acid (equiv)
Solvent
Time (h)
T (°C)
Yieldsb (%)
drc
1
2
3
4
5
6
7
8
—
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Toluene
ClCH2CH2Cl
48
48
48
48
48
5
10
10
35
39
40
40
40
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ78
ꢀ50
ꢀ78
ꢀ78
n.r.d
Trace
Trace
Trace
Trace
99
91
93
88
93
—
—
—
—
CuI (0.5)
CuBr (0.5)
CuCl (0.5)
ZnCl2ꢁEt2O (0.5)
FeCl3 (0.2)
BF3ꢁEt2O (0.5)
SnCl4 (0.5)
AlCl3 (0.5)
AlCl3 (0.5)
AlCl3 (0.3)
AlCl3 (0.5)
AlCl3 (0.5)
—
83:17:0:0
60:40:0:0
83:17:0:0
99:1:0:0
90:10:0:0
83:17:0:0
90:10:0:0
83:17:0:0
9
10
11
12
13
70
90
99
a
b
c
Unless otherwise noted all the reactions were performed with 0.3 mmol of 3b, 0.6 mmol silyl dienolate in 3 mL solvent.
After purification by chromatography.
Diastereomeric ratio (dr) values were determined from the crude product by 1H NMR.
No reaction.
d
We initially investigated the reaction of O-pivaloylated N-galacto-
sylimine 3b (R = p-NO2C6H4) with 1-trimethylsilyloxy-1,3-butadi-
ene 4 in THF without the aid of Lewis acid and no product 5b
was detected (Table 1, entry 1). Since the nucleophilicity of silyl
dienolate 4 is low and the electrophilicity of imines 3 is only mod-
erate, several kinds of Lewis acid are examined for the reaction of
the O-pivaloylated N-galactosylimine 3b with silyloxy-1,3-butadi-
ene 4 in THF at ꢀ50 °C.
bearing both electron-rich and electron-poor aromatic groups,
gave the corresponding asymmetric vinylogous Mannich products
5b–m in good to high yields and diastereoselectivities (Table 2,
5b–m). As for the aldimine in which R was a phenyl group, rela-
tively lower yield and high diastereoselectivity was realized under
identical conditions (Table 2, 5a). Particularly, this process was
efficient for cinnamaldehyde and afforded the desired product
with high diastereoselectivity (94:6:0:0) in 85% yield (Table 2,
5n). Notably, the aldimine derived from heteroaromatic aldehyde
gave the adducts in good yield but with poor diastereoselectivity
(Table 2, 5o). Furthermore, the reaction of Schiff base 3 of aliphatic
aldehyde with silyl dienolate 4 led to the product in very poor
yield, only anomerization and decomposition occurred. The prod-
ucts 5 contained exclusively E double bonds, and accordingly no
cyclization to the corresponding 5,6-dihydro-2-pyridones was
observed.
The results revealed that CuI, CuBr, CuCl and ZnCl2ꢁEt2O only
caused anomerization of the Schiff base 3b, and no product of 5b
was observed (Table 1, entries 2–5). Other Lewis acids tested
(e.g., FeCl3, BF3ꢁEt2O, SnCl4 and AlCl3)16 were able to promote the
addition and gave good yields and moderate to high diastereose-
lectivities (Table 1, entries 6–9).
Since AlCl3 gave the higher diastereoselectivity (dr = 99:1:0:0)
and higher yield (88%) compared with other Lewis acids, it was
used in further investigations. Particularly, when decreasing the
reaction temperature to ꢀ78 °C and decreasing the loading amount
of catalyst, AlCl3 (30 mol %) was able to catalyze the reaction to
give the desired product in good yields with lower diastereoselec-
tivities (Table 1, entries 10 and 11).
The ratio of the obtained diastereomers 5b was determined by
HPLC from the crude mixture of the reaction. It should be noted
that because of the anomeric carbon and one stereogenic center
created at the vinylogous Mannich products 5, the four anomeric
A synthetically relevant advantage of using O-pivaloylated D-
galactosylamine as the chiral auxiliary is the facile deprotection
of the vinylogous Mannich products 5 by simple treatment with
MeONa in MeOH. We submitted 5b to Wittig reaction with (triphe-
nylphosphoranylidene)acetate 6 in ethanol and obtained ethyl-
(2E,4E)-7-galactosylamino-7-(p-nitrophenyl)hepta-2,4-dienoate
7b in 90% yield. Subsequently, adduct 7b was converted to the
eight-membered lactam 9b by hydrogenation of the double bond
catalyzed by Pd/C and subsequently cyclized to (S)-8-(p-nitro-
phenyl)azocan-2-one 9b in 60% yield (Scheme 1). The preparation
of the known eight-membered lactam 9b allowed us to establish
the chiral center absolute configuration of the starting adduct 7b
as S, by analogy, that of the rest of VMR products 5.17
We proposed possible pathways for this vinylogous Mannich
reaction based on the previous related work in Figure 1.13 The pre-
ferred formation of the configured diastereomer of 5 can be ratio-
nalized by an attack of silyl dienolate from Si side of N-
galactosylaldimines 3. In the transition state, the aluminium atom
has hexa-coordination of which the sites are occupied by the imine
nitrogen and carbonyloxygen (C-2 and C-6) of the pivaloyloxy
groups respectively, and one of the three chlorines may be re-
moved when silyl dienolate was introduced. According to this
diastereomers have the bS, bR,
aS and aR configurations. The
experiment results showed that the corresponding
a-anomer
could be restricted in this reaction.
With the best Lewis acid AlCl3 being identified, a solvent screen
was undertaken. The results showed that toluene and 1,2-dichloro-
ethane provided 5b in high yields and lower diastereomeric ratios
(Table 1, entries 12 and 13). Among the solvents tested, THF was
found to be the best with respect to catalytic activity and asym-
metric induction.
With the optimized conditions in hand, we then investigated
the scope and limitations of this reaction with various aldimines
3 and silyloxy-1,3-butadiene 4, and the results were summarized
in Table 2. It was found that O-pivaloylated N-galactosylimine 3,

B. Cui et al. / Carbohydrate Research 374 (2013) 1–7
3
Table 2
The vinylogous Mannich reaction of N-(2,3,4,6-tetra-O-pivaloyl-D-galactosyl)aldimines 3a–o
OPiv
PivO
OPiv
PivO
2.0 equiv
H
N
OPiv
OTMS
4
O
O
S
N
R
PivO
PivO
AlCl3 0.5 equiv
-50 ¡ãC, THF
OPiv
R
H
O
5
3
Product
R
Time (h)
Yielda (%)
drb
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
Ph
55
35
35
36
53
34
58
50
46
30
48
54
35
58
46
71
88
94
90
78
90
89
97
92
99
94
98
99
85
74
99:1:0:0
99:1:0:0
95:5:0:0
94:6:0:0
95:5:0:0
99:1:0:0
98:2:0:0
99:1:0:0
96:4:0:0
95:5:0:0
99:1:0:0
99:1:0:0
88:12:0:0
94:6:0:0
56:27:6:11
p-NO2 phenyl
p-F phenyl
p-Br phenyl
p-CF3 phenyl
p-CH3 phenyl
o-NO2 phenyl
o-Cl phenyl
o-Br phenyl
o-CH3 phenyl
m-F phenyl
m-Cl phenyl
m-CH3 phenyl
trans-2-Phenyl-vinyl
Furane-2-yl
a
After purification by chromatography.
Diastereomeric ratio determined from the crude product by HPLC.
b
OPiv
O
OPiv
O
PivO
PivO
PivO
PivO
H
N
H
N
O
OPiv
O
OEt
PivO
PivO
CO2Et
1. Pd/C, H2
OPiv
OPiv
Ph3P
HN
+
6
OH
OPiv
O
O
2. MeONa
MeOH
EtOH
O2N
NO2
7b
NO2
5b
9b
8
Scheme 1. Synthesis of (S)-8-(p-nitrophenyl)azocan-2-one 9b.
deprotection allows the resulting products to be readily trans-
formed into optically active eight-membered lactam derivatives.
Si
O
Cl
tBu
Cl
O
Cl
3. Experimental
O
PivO
PivO
Al
O
O
N
Ph
3.1. General experimental methods
O
H
All reactions were carried out under an inert atmosphere and in
heat-dried glassware. Anhydrous THF was obtained by distillation
from sodium silk. Flash column chromatography was performed
tBu
Figure 1. Plausible reaction mechanism.
on silica gel (particle size 10–40 lm, Ocean Chemical Factory of
rationalization, the SN20-type attack of silyl dienolate from the back
side of the plane of C@N is initiated. Based on these results, this
hypothesis would explain the course of the main isomer synthesis.
The mechanism indicates that the pivaloyl group in the aldimines 3
plays a significant role in controlling the diastereoselective addi-
tion of silyl dienolate to N-galactosylaldimines 3.
In conclusion, we have developed a new efficient synthetic pro-
tocol for preparation of chiral eight-membered lactam derivative in
high yield and high enantiostereoselectivity, utilizing AlCl3 as the
Qingdao, China). Nitrogen gas (99.999%) was purchased from Boc
Gas Inc. 1H, and 13C spectra were recorded on Bruker-400
(400 MHz for 1H, 101 MHz for 13C) spectrometers. Chemical shifts
were reported in ppm downfield from internal Si(CH3)4. Mass spec-
tra were recorded on a LCQ advantage spectrometer with ESI re-
source. HR-MS were recorded on APEXII and ZAB-HS spectrometer.
Melting points were determined on a T-4 melting point apparatus
(uncorrected). Optical rotations were recorded on a Perkin Elemer
241 Polarimeter. HPLC (Chiralcel AD-H, hexane/iPrOH, 92:8 v/v,
1.0 mL/min, UV 220 nm) analyses were recorded on Agilent 1100
series.
promoter and O-pivaloylated D-galactosylamine 1 as chiral auxil-
iary via vinylogous Mannich reactions. The O-pivaloylated galacto-
sylamine 1 is an effective chiral template in the synthesis of chiral
N-galactosyl a,b-unsaturated d-amino aldehyde derivatives 5. AlCl3
3.2. General procedure for the preparation of O-pivaloylated N-
can form the hexa-coordination intermediate inducing the S con-
figuration at the chiral center of the corresponding asymmetric
vinylogous Mannich products 5 by attack at the Si-side of the
C@N plane of the imine carbon atom. The mild carbohydrate
galactosylimines 3
To a solution of 2,3,4,6-tetra-O-pivaloyl-b-
amine 1 (0.515 g, 1 mmol) and aldehyde 2 (1.3 mmol) in 2-propanol
D-galactopyranosyl

4
B. Cui et al. / Carbohydrate Research 374 (2013) 1–7
3
0
0
(2.5 mL), 2–3 drops of acetic acid were added and the mixture was
stirred at room temperature for about 0.5 h. The appearance of a pre-
cipitate from the solution indicated the formation of 3, after the pre-
cipitate was filtered off, then washed with ice cold 2-propanol and
dried in vacuum, N-galactosylaldimines 3 was isolated as a white
solid.
CDCl3): d = 9.42 (d, 1H, J4 ,5 = 7.7 Hz, CHO), 7.24 (t, 2H,
3J = 8.5 Hz, Ph), 7.03 (t, 2H, 3J = 8.5 Hz, Ph), 6.59 (dt, 1H,
3
3
3
0
0
0
0
J3 ,4 = 15.8 Hz,
J2 ,3 = 7.2 Hz,
CH@CH),
6.08
(dd,
1H,
3
3
0
0
0
0
J3 ,4 = 15.8 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.36 (d, 1H, J3,4 = 2.7 Hz,
4-H), 5.01–5.09 (m, 2H, 2-H, 3-H), 4.33 (t, 1H, J1 ,2 = 6.8 Hz,
CHNH), 4.09–4.14 (m, 1H, 6b-H), 3.96–4.01 (m, 1H, 6a-H), 3.81
3
0
0
3
3
(d, 1H, J1,2 = 6.6 Hz, 1-H), 3.71 (t, 1H, J5,6 = 6.8 Hz, 5-H), 2.66 (t,
3
0
0
3.3. General procedure for the synthesis of b-N-glycosidic
linkages 5-amino-5-substituted pent-2-enal 5
J1 ,2 = 6.8 Hz, 2H, CH2CH@CH), 2.20 (s, 1H, NH), 1.27 (s, 9H,
C(CH3)3), 1.20 (s, 18H, 2C(CH3)3), 1.10 (s, 9H, C(CH3)3). 13C NMR
(101 MHz, CDCl3): d = 193.29, 177.83, 177.64, 177.06, 176.81
(C@O), 161.08 (1JC–F = 246.4 Hz), 152.81, 136.17 (1JC–F = 3.1 Hz),
135.20, 129.04 (1JC–F = 7.9 Hz), 115.44 (1JC–F = 21.4 Hz) (Ph,
CH@CH), 86.07, 71.72, 71.15, 68.86, 67.26, 61.64, 55.67 (C–O, C–
N), 41.37, 39.03, 38.80, 38.69, 27.22, 27.18, 27.09, 27.06, 19.14.
ESIMS: [M+H]+ m/z 692.4. HRESIMS: [M+Na]+ calcd for
A solution of N-galactosylaldimine 3 (0.3 mmol), and AlCl3
(20 mg, 0.15 mmol) in THF (3 mL) was cooled to ꢀ50 °C under nitro-
gen protection, and trimethylsilaneoxy-1,3-butadiene 4 (85.2 mg,
0.6 mmol) was added. The mixture was stirred at this temperature
until no starting material was present by TLC (about 34–58 h). The
mixture was hydrolyzedwith aqueous saturated solution of NaHCO3
(5 mL). Then the mixture was stirred at room temperature for
15 min. The aqueous phase was extracted with AcOEt (3 ꢂ 5 mL),
and the organic layers were combined, dried with anhydrous MgSO4,
filtered, and concentrated in vacuo. After purification by flash col-
umn chromatography on silica gel [petroleum ether/ethyl acetate,
15:1 (V/V)], pure products 5 were abtained.
C
37H54FNO10Na+: 714.3624; found, 714.3629.
3.3.4. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
D
-
galactopyranosyl)amino]-5-(p-bromo phenyl)-pent-2-enal (5d)
Yield: 202 mg, 90%, white oil, Rf = 0.5 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ28.8° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0
CDCl3): d = 9.34 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.39 (d, 2H,
3J = 8.3 Hz, Ph), 7.07 (d, 2H, 3J = 8.3 Hz, Ph), 6.50 (dt, 1H,
3
3
3
0
0
0
0
3.3.1. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
D
-
J3 ,4 = 15.7 Hz,
J2 ,3 = 7.1 Hz,
CH@CH),
5.98
(dd,
1H,
3
3
0
0
0
0
galactopyranosyl)amino]-5-phenyl pent-2-enal (5a)
J3 ,4 = 15.7 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.28 (d, 1H, J3,4 = 2.4 Hz,
4-H), 4.94–5.02 (m, 2H, 2-H, 3-H), 4.23 (t, 1H, J1 ,2 = 6.6 Hz,
CHNH), 4.01–4.06 (m, 1H, 6b-H), 3.88–3.93 (m, 1H, 6a-H), 3.73
3
0
0
Yield: 143 mg, 71%, white oil, Rf = 0.3 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ31.7° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
3
3
0
0
CDCl3): d = 9.33 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.18–7.26 (m, 5H,
(d, 1H, J1,2 = 3.9 Hz, 1-H), 3.63 (t, 1H, J5,6 = 6.8 Hz, 5-H), 2.57 (t,
3
3
3
0
0
0
0
0
0
Ph), 6.54 (dt, 1H, J3 ,4 = 15.6 Hz, J2 ,3 = 7.1 Hz, CH@CH), 5.98 (dd,
J1 ,2 = 6.6 Hz, 2H, CH2CH@CH), 2.11 (s, 1H, NH), 1.19 (s, 9H,
C(CH3)3), 1.12 (s, 9H, C(CH3)3), 1.11 (s, 9H, C(CH3)3), 1.02 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.18, 177.79, 177.63,
177.02, 176.79 (C@O), 152.45, 139.64, 135.31, 131.80, 129.24,
121.79 (Ph, CH@CH), 86.09, 71.77, 71.13, 68.69, 67.26, 61.63,
55.79 (C–O, C–N), 41.18, 39.04, 38.82, 38.69, 27.25, 27.20, 27.12,
27.07, 21.31. ESIMS: [M+Na]+ m/z 774.3. HRESIMS: [M+Na]+ calcd
for C37H54BrNO10Na+: 774.2823; found, 774.2829.
3
3
0
0
0
0
1H,
J3 ,4 = 15.6 Hz,
J4 ,5 = 7.8 Hz, CH@CH), 5.27 (d, 1H,
3J3,4 = 2.9 Hz, 4-H), 4.92–5.05 (m, 2H, 2-H, 3-H), 4.25 (t, 1H,
J1 ,2 = 6.8 Hz, CHNH), 4.00–4.07 (m, 1H, 6b-H), 3.88–3.96 (m, 1H,
6a-H), 3.75 (d, 1H, J1,2 = 8.4 Hz, 1-H), 3.62 (t, 1H, J5,6 = 6.7 Hz, 5-
H), 2.60 (t, J1 ,2 = 6.8 Hz, 2H, CH2CH@CH), 2.14 (s, 1H, NH), 1.20
(s, 9H, C(CH3)3), 1.13 (s, 18H, 2C(CH3)3), 1.02 (s, 9H, C(CH3)3). 13C
NMR (101 MHz, CDCl3): d = 193.40, 177.85, 177.70, 177.08,
176.84 (C@O), 153.27, 140.49, 135.08, 128.60, 127.99, 127.59 (Ph,
CH@CH), 86.25, 71.73, 71.22, 68.73, 67.37, 61.73, 56.42 (C–O, C–
N), 41.38, 39.05, 38.82, 38.70, 27.25, 27.21, 27.12, 27.08, 14.19.
ESIMS: [M+Na]+ m/z 696.33. HRESIMS: [M+Na]+ calcd for
C37H55NO10Na+: 696.3718; found, 696.3721.
3
0
0
3
3
3
0
0
3.3.5. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(p-trifluoromethylphenyl)-pent-2-
enal (5e)
Yield: 173 mg, 78%, white oil, Rf = 0.4 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ27.6° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0
3.3.2. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
D
-
CDCl3): d = 9.35 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.53 (d, 2H,
galactopyranosyl)amino]-5-(p-nitrophenyl)-pent-2-enal (5b)
Yield: 189 mg, 88%, white oil, Rf = 0.3 (petroleum ether/ethyl
3J = 8.2 Hz, Ph), 7.33 (d, 2H, 3J = 8.2 Hz, Ph), 6.52 (dt, 1H,
3
3
3
0
0
0
0
J3 ,4 = 15.7 Hz,
J2 ,3 = 7.2 Hz,
CH@CH),
6.01
(dd,
1H,
acetate = 15:1). ½a D25
ꢃ
ꢀ26.6° (c 1.0, CHCl3). 1H NMR (400 MHz,
J3 ,4 = 15.7 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.28 (d, 1H, J3,4 = 2.6 Hz,
4-H), 4.95–5.04 (m, 2H, 2-H, 3-H), 4.34 (t, 1H, J1 ,2 = 6.6 Hz,
CHNH), 4.02–4.07 (m, 1H, 6b-H), 3.89–3.93 (m, 1H, 6a-H), 3.74 (t,
3
3
0
0
0
0
3
3
0
0
0
0
CDCl3): d = 9.44 (d, 1H, J4 ,5 = 7.7 Hz, CHO), 8.21 (d, 2H,
3J = 8.5 Hz, Ph), 7.46 (d, 2H, 3J = 8.5 Hz, Ph), 6.59 (dt, 1H,
3
3
3
3
3
0
0
0
0
J3 ,4 = 15.7 Hz,
J2 ,3 = 7.1 Hz,
0
CH@CH),
6.08
(dd,
1H,
1H, J1,2 = 8.5 Hz, 1-H), 3.64 (t, 1H, J5,6 = 6.7 Hz, 5-H), 2.61 (t,
3
3
3
0
0
0
0
0
J3 ,4 = 15.7 Hz, J4 ,5 = 7.7 Hz, CH@CH), 5.36 (d, 1H, J3,4 = 2.8 Hz,
J1 ,2 = 6.6 Hz, 2H, CH2CH@CH), 2.16 (s, 1H, NH), 1.20 (s, 9H,
C(CH3)3), 1.13 (s, 9H, C(CH3)3), 1.12 (s, 9H, C(CH3)3), 1.02 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.11, 177.80, 177.67,
177.04, 176.79 (C@O), 152.06, 144.95, 135.43, 130.12, 127.84,
125.63 (Ph, CH@CH), 125.60, 86.18, 71.80, 71.09, 68.70, 67.20,
61.57, 55.94 (C–O, C–N), 41.17, 39.04, 38.82, 38.69, 27.22, 27.17,
27.08, 27.05, 22.63. ESIMS: [M+Na]+ m/z 764.2. HRESIMS:
[M+Na]+ calcd for C38H54F3NO10Na+: 764.3592; found, 764.3595.
3
0
0
4-H), 5.02–5.11 (m, 2H, 2-H, 3-H), 4.48 (t, 1H, J1 ,2 = 6.7 Hz,
CHNH), 4.10–4.15 (m, 1H, 6b-H), 3.95–3.99 (m, 1H, 6a-H), 3.81
3
3
(d, 1H, J1,2 = 6.6 Hz, 1-H), 3.71 (t, 1H, J5,6 = 6.7 Hz, 5-H), 2.70 (t,
3
0
0
J1 ,2 = 6.7 Hz, 2H, CH2CH@CH), 2.27 (s, 1H, NH), 1.27 (s, 9H,
C(CH3)3), 1.21 (s, 9H, C(CH3)3), 1.19 (s, 9H, C(CH3)3), 1.10 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 192.94, 177.75, 177.62,
177.00, 176.74 (C@O), 151.43, 148.59, 147.63, 135.61, 128.29,
123.87 (Ph, CH@CH), 86.24, 71.83, 71.05, 68.70, 67.12, 61.49,
55.81 (C–O, C–N), 41.36, 41.01, 39.02, 38.83, 38.67, 27.23, 27.16,
27.07, 27.04. ESIMS: [M+Na]+ m/z 741.2. HRESIMS: [M+Na]+ calcd
for C37H54N2O12Na+: 741.3569; found, 741.3574.
3.3.6. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(p-methylphenyl)-pent-2-enal (5f)
Yield 185 mg, 90%, white oil, Rf = 0.3 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ32.3° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0
3.3.3. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
D
-
CDCl3): d = 9.30 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.03 (s, 4H, Ph), 6.50
3
3
0
0
0
0
galactopyranosyl)amino]-5-(p-fluorophenyl)-pent-2-enal (5c)
Yield: 195 mg, 94%, white oil, Rf = 0.3 (petroleum ether/ethyl
(dt, 1H, J3 ,4 = 15.7 Hz, J2 ,3 = 7.2 Hz, CH@CH), 5.95 (dd, 1H,
J3 ,4 = 15.7 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.23 (d, 1H, J3,4 = 2.1 Hz,
4-H), 4.89–4.99 (m, 2H, 2-H, 3-H), 4.18 (t, 1H, J1 ,2 = 6.6 Hz,
3
3
3
0
0
0
0
acetate = 15:1). ½a D25
ꢃ
ꢀ33.5° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0

B. Cui et al. / Carbohydrate Research 374 (2013) 1–7
5
CHNH), 3.98–4.02 (m, 1H, 6b-H), 3.86–3.91 (m, 1H, 6a-H), 3.71 (d,
1H, J1,2 = 8.4 Hz, 1-H), 3.58 (t, 1H, J5,6 = 6.7 Hz, 5-H), 2.55 (t,
(C@O), 152.84, 140.04, 135.24, 133.09, 129.18, 128.66, 127.58,
124.05 (Ph, CH@CH), 86.67, 71.69, 71.25, 68.86, 67.15, 61.35,
54.55 (C–O, C–N), 40.12, 39.06, 38.84, 38.72, 38.69, 27.26, 27.21,
27.13, 27.09. ESIMS: [M+Na]+ m/z 774.1. HRESIMS: [M+Na]+ calcd
for C37H54BrNO10Na+: 774.2823; found, 774.2830.
3
3
3
0
0
J1 ,2 = 6.6 Hz, 2H, CH2CH@CH), 2.25(s, 3H, CH3), 2.06 (s, 1H, NH),
1.16 (s, 9H, C(CH3)3), 1.10 (s, 18H, 2C(CH3)3), 0.99 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.53, 177.88, 177.71,
177.10, 176.87 (C@O), 153.59, 137.69, 137.23, 135.00, 129.30,
127.55 (Ph, CH@CH), 86.13, 71.69, 71.21, 68.68, 67.39, 61.76,
56.09 (C–O, C–N), 41.39, 39.05, 38.82, 38.70, 27.26, 27.21, 27.13,
27.08, 21.31, 19.16. ESIMS: [M+Na]+ m/z 710.2. HRESIMS:
[M+Na]+ calcd for C38H57NO10Na+: 710.3875; found, 710.3880.
3.3.10. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(o-methylphenyl)-pent-2-enal (5j)
Yield: 204 mg, 99%, white oil, Rf = 0.5 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ26.5° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0
CDCl3): d = 9.41 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.37–7.39 (m, 1H,
3
0
0
3.3.7. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
D-
Ph), 7.15–7.19 (m, 3H, Ph), 6.62 (dt, 1H, J3 ,4 = 15.6 Hz,
3
3
3
0
0
0
0
0
0
galactopyranosyl)amino]-5-(o-nitrophenyl)-pent-2-enal (5g)
Yield: 191 mg, 89%, white oil, Rf = 0.3 (petroleum ether/ethyl
J2 ,3 = 7.2 Hz, CH@CH), 6.08 (dd, 1H, J3 ,4 = 15.6 Hz, J4 ,5 = 7.8 Hz,
3
CH@CH), 5.34 (d, 1H, J3,4 = 2.1 Hz, 4-H), 5.00–5.08 (m, 2H, 2-H, 3-
acetate = 15:1). ½a D25
ꢃ
ꢀ41.2° (c 1.0, CHCl3). 1H NMR (400 MHz,
H), 4.65 (t, 1H, J1 ,2 = 6.6 Hz, CHNH), 4.06–4.11 (m, 1H, 6b-H),
3
0
0
3
3
CDCl3): d = 9.39 (d, 1H, J4 ,5 = 6.6 Hz, CHO), 7.75 (d, 1H, 3J = 7.9,
3.96–4.00 (m, 1H, 6a-H), 3.80 (d, 1H, J1,2 = 8.1 Hz, 1-H), 3.72 (t,
0
0
Ph), 7.63 (d, 1H, 3J = 7.8, Ph), 7.51 (t, 1H, 3J = 7.9, Ph), 7.37 (t, 1H,
1H, J5,6 = 6.9 Hz, 5-H), 2.65 (t, J1 ,2 = 6.6 Hz, 2H, CH2CH@CH),
2.32 (s, 3H, CH3), 2.17 (s, 1H, NH), 1.26 (s, 9H, C(CH3)3), 1.19 (s,
9H, C(CH3)3), 1.16 (s, 9H, C(CH3)3), 1.09 (s, 9H, C(CH3)3). 13C NMR
(101 MHz, CDCl3): d = 193.44, 177.90, 177.71, 177.10, 176.79
(C@O), 153.43, 138.47, 136.00, 135.06, 130.56, 127.43, 126.77,
126.30 (Ph, CH@CH), 86.38, 71.47, 71.19, 68.75, 67.17, 61.43,
51.18 (C–O, C–N), 40.64, 39.05, 38.83, 38.67, 27.26, 27.20, 27.15,
27.08, 19.38, 19.15. ESIMS: [M+Na]+ m/z 710.2. HRESIMS:
[M+Na]+ calcd for C38H57NO10Na+: 710.3875; found, 710.3879.
3
3
0
0
3J = 7.8, Ph), 6.67 (dt, 1H, J3 ,4 = 15.6 Hz, J2 ,3 = 7.0 Hz, CH@CH),
3
3
0
0
0
0
3
3
0
0
0
0
6.02 (dd, 1H, J3 ,4 = 15.6 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.28 (s, 1H,
3
0
0
4-H), 4.94–5.00 (m, 2H, 2-H, 3-H), 4.83 (t, 1H, J1 ,2 = 6.4 Hz,
CHNH), 3.99–4.03 (m, 1H, 6b-H), 3.90–3.94 (m, 1H, 6a-H), 3.76
(s, 1H, 1-H), 3.72 (t, 1H, J5,6 = 7.0 Hz, 5-H), 2.64–2.76 (m, 2H,
3
CH2CH@CH), 2.18 (s, 1H, NH), 1.19 (s, 9H, C(CH3)3), 1.10 (s, 18H,
2C(CH3)3), 1.02 (s, 9H, C(CH3)3). 13C NMR (101 MHz, CDCl3):
d = 193.25, 177.84, 177.58, 177.08, 176.76 (C@O), 152.28, 149.90,
136.43, 135.42, 132.73, 129.10, 128.57, 124.14 (Ph, CH@CH),
86.77, 71.78, 71.17, 68.77, 67.03, 61.21, 50.88 (C–O, C–N), 40.86,
39.03, 38.80, 38.70, 38.66, 27.22, 27.16, 27.13, 27.05. ESIMS:
[M+Na]+ m/z 741.2. HRESIMS: [M+Na]+ calcd for C37H54N2O12Na+:
741.3569; found, 741.3572.
3.3.11. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(m-fluorophenyl)-pent-2-enal (5k)
Yield: 194 mg, 94%, white oil, Rf = 0.3 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ27.1° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
0
0
CDCl3): d = 9.44 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.31 (s, 1H, Ph),
3.3.8. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(o-chlorinephenyl)-pent-2-enal
(5h)
3
3
0
0
0
0
6.98–7.03 (m, 3H, Ph), 6.59 (dt, 1H, J3 ,4 = 15.6 Hz, J2 ,3 = 7.1 Hz,
CH@CH), 6.07 (dd, 1H, J3 ,4 = 15.6 Hz, J4 ,5 = 7.8 Hz, CH@CH),
3
3
0
0
0
0
5.35 (s, 1H, 4-H), 5.01–5.09 (m, 2H, 2-H, 3-H), 4.33 (t, 1H,
Yield: 205 mg, 97%, white oil, Rf = 0.2 (petroleum ether/ethyl
3
0
0
J1 ,2 = 6.4 Hz, CHNH), 4.08–4.14 (m, 1H, 6b-H), 3.96–4.02 (m, 1H,
acetate = 15:1). ½a D25
ꢃ
ꢀ35.5° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
6a-H), 3.80–3.87 (m, 1H, 1-H), 3.71 (t, 1H, J5,6 = 7.0 Hz, 5-H),
3
0
0
CDCl3): d = 9.43 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.45–7.47 (m, 1H,
3
0
0
2.66 (t, 2H, J2 ,3 = 7.1 Hz, CH2CH@CH), 2.16 (s, 1H, NH), 1.27 (s,
9H, C(CH3)3), 1.20 (s, 9H, C(CH3)3), 1.19 (s, 9H, C(CH3)3), 1.10 (s,
9H, C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.27, 177.85,
177.74, 177.09, 176.83 (C@O), 161.88 (1JC–F = 246.9 Hz), 152.52,
143.48 (1JC–F = 6.6 Hz), 135.28, 130.10 (1JC–F = 8.0 Hz), 123.25,
114.87 (1JC–F = 21.2 Hz), 114.07 (1JC–F = 21.6 Hz) (Ph, CH@CH),
86.19, 71.81, 71.17, 68.68, 67.28, 61.67, 55.91 (C–O, C–N), 41.25,
39.05, 38.94, 38.83, 38.70, 27.23, 27.19, 27.10, 27.07. ESIMS:
[MꢀF]ꢀ m/z 671.9. HRESIMS: [M+Na]+ calcd for C37H54FNO10Na+:
714.3624; found, 714.3628.
Ph), 7.35–7.37 (m, 1H, Ph), 7.22–7.25 (m, 2H, Ph), 6.68 (dt, 1H,
3
3
3
0
0
0
0
J3 ,4 = 15.7 Hz,
J2 ,3 = 7.2 Hz,
0
CH@CH),
6.08
(dd,
1H,
3
0
0
0
J3 ,4 = 15.7 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.37 (s, 1H, 4-H), 5.04–
3
0
0
5.08 (m, 2H, 2-H, 3-H), 4.90 (t, 1H, J1 ,2 = 6.5 Hz, CHNH), 4.09–
4.13 (m, 1H, 6b-H), 3.98–4.02 (m, 1H, 6a-H), 3.88 (s, 1H, 1-H),
3
3
0
0
3.78 (t, 1H, J5,6 = 6.9 Hz, 5-H), 2.61 (t, 2H, J1 ,2 = 6.5 Hz,
3
0
JN,1 = 13.0 Hz, CH2CH@CH), 2.13 (s, 1H, NH), 1.27 (s, 9H,
C(CH3)3), 1.18 (s, 9H, C(CH3)3), 1.17 (s, 9H, C(CH3)3), 1.10 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.37, 177.93, 177.68,
177.15, 176.84 (C@O), 152.87, 138.52, 135.25, 133.62, 129.82,
128.78, 128.38, 126.95 (Ph, CH@CH), 86.79, 71.81, 71.28, 68.88,
67.26, 61.53, 52.09 (C–O, C–N), 39.98, 39.08, 38.85, 38.74, 38.71,
27.27, 27.22, 27.19, 27.11. ESIMS: [M+Na]+ m/z 730.3. HRESIMS:
[M+Na]+ calcd for C37H54ClNO10Na+: 730.3328; found, 730.3333.
3.3.12. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-5-(m-chlorinephenyl)-pent-2-enal
(5l)
Yield: 207 mg, 98%, white oil, Rf = 0.2 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ30.5° (c 1.0, CHCl3). 1H NMR (400 MHz,
3.3.9. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-
3
0
0
CDCl3): d = 9.46 (d, 1H, J4 ,5 = 7.8 Hz, CHO), 7.31–7.32 (m, 3H,
galactopyranosyl)amino]-5-(o-bromophenyl)-pent-2-enal (5i)
Yield: 207 mg, 92%, white oil, Rf = 0.3 (petroleum ether/ethyl
3
0
0
Ph), 7.13–7.15 (m, 1H, Ph), 6.62 (dt, 1H, J3 ,4 = 15.7 Hz,
3
3
3
acetate = 15:1). ½a D25
ꢃ
ꢀ31.7° (c 1.0, CHCl3). 1H NMR (400 MHz,
0
0
0
0
0
0
J2 ,3 = 7.0 Hz, CH@CH), 6.11 (dd, 1H, J3 ,4 = 15.7 Hz, J4 ,5 = 7.8 Hz,
3
3
CDCl3): d = 9.44 (d, 1H, J4 ,5 = 6.6 Hz, CHO), 7.55 (d, 1H, 3J = 7.9,
0
0
CH@CH), 5.39 (d, 1H, J3,4 = 1.9 Hz, 4-H), 5.08–5.12 (m, 2H, 2-H, 3-
3
Ph), 7.45 (d, 1H, 3J = 7.7, Ph), 7.29 (t, 1H, 3J = 7.9, Ph), 7.15 (t, 1H,
0
0
H), 4.34 (t, 1H, J1 ,2 = 6.5 Hz, CHNH), 4.11–4.16 (m, 1H, 6b-H),
3J = 7.7, Ph), 6.70 (dt, 1H, J3 ,4 = 15.6 Hz, J2 ,3 = 7.1 Hz, CH@CH),
3
3
0
0
0
0
3.00–4.04 (m, 1H, 6a-H), 3.84–3.89 (m, 1H, 1-H), 3.75 (t, 1H,
3
3
3
3
0
0
0
0
0
0
J5,6 = 6.8 Hz, 5-H), 2.68 (t, J1 ,2 = 6.5 Hz, 2H, CH2CH@CH), 2.20 (s,
6.08 (dd, 1H, J3 ,4 = 15.6 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.37(s, 1H,
3
0
0
1H, NH), 1.30 (s, 9H, C(CH3)3), 1.24 (s, 9H, C(CH3)3), 1.23 (s, 9H,
C(CH3)3), 1.13 (s, 9H, C(CH3)3). 13C NMR (101 MHz, CDCl3):
d = 193.29, 177.88, 177.77, 177.11, 176.85 (C@O), 152.45, 142.95,
135.34, 134.79, 129.88, 128.25, 127.34, 125.88 (Ph, CH@CH),
86.13, 71.83, 71.17, 68.65, 67.29, 61.69, 55.87 (C–O, C–N), 41.27,
39.06, 38.86, 38.76, 38.72, 27.29, 27.20, 27.13, 27.08. ESIMS:
4-H), 5.04–5.10 (m, 2H, 2-H, 3-H), 4.87 (t, 1H, J1 ,2 = 6.3 Hz,
CHNH), 4.11–4.15 (m, 1H, 6b-H), 3.99–4.03 (m, 1H, 6a-H), 3.87
3
(s, 1H, 1-H), 3.80 (t, 1H, J5,6 = 7.9 Hz, 5-H), 2.67–2.72 (m, 2H,
CH2CH@CH), 2.18 (s, 1H, NH), 1.27 (s, 9H, C(CH3)3), 1.19 (s, 9H,
C(CH3)3), 1.18 (s, 9H, C(CH3)3), 1.10 (s, 9H, C(CH3)3). 13C NMR
(101 MHz, CDCl3): d = 193.37, 177.89, 177.66, 177.12, 176.80

6
B. Cui et al. / Carbohydrate Research 374 (2013) 1–7
[M+Na]+ m/z 730.4. HRESIMS: [M+Na]+ calcd for C37H54ClNO10Na+:
3.4. General procedure for the synthesis of (S)-8-(p-
730.3328; found, 730.3330.
nitrophenyl)azocan-2-one 9b
3.3.13. (2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-
galactopyranosyl)amino]-5-(m-methylphenyl)-pent-2-enal
(5m)
D
-
A solution of compound 7b (316 mg, 0.4 mmol) in dry methanol
(5 mL) was reduced with H2 on Pd/C (10%). The reaction was stirred
for 10 h (TLC control) at room temperature. Then filtered, and con-
centrated in vacuo to yield the crude product. Then a solution of
the crude product in dry ethanol (5 mL) was treated with freshly
prepared (0.5 M) solution of sodium ethoxide (5 mL). The mixture
was stirred at room temperature for 4 h (TLC control). Then a few
drops of water were added to the mixture, and the mixture was
neutralized with acetic acid. The mixture was stirred at room tem-
perature for another 4 h. The mixture was extracted with EtOAc
(3 ꢂ 5 mL) and the organic phase was washed with saturated aque-
ous NaHCO3 (3 ꢂ 5 mL), dried over MgSO4, filtered, and concen-
trated in vacuo to yield the crude product 9b. The residue was
purified by column chromatography on silica gel [ethyl acetate/
MeOH = 30/1], yielding the corresponding compound 9b (60 mg,
60% yield) as a white solid.
Yield: 204 mg, 99%, white oil, Rf = 0.4 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ39.8° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
3
0
0
0
0
CDCl3): d = 9.41 (dd, 1H, J4 ,5 = 7.7 Hz, J3 ,5 = 3.7 Hz, CHO), 7.19–
7.23 (m, 1H, Ph), 7.12–7.13 (m, 2H, Ph), 7.00–7.07 (m, 1H, Ph),
3
3
0
0
0
0
6.60 (dt, 1H, J3 ,4 = 15.6 Hz, J2 ,3 = 6.6 Hz, CH@CH), 6.06 (dd, 1H,
3
3
3
0
0
0
0
J3 ,4 = 15.6 Hz, J4 ,5 = 7.8 Hz, CH@CH), 5.34 (d, 1H, J3,4 = 2.3 Hz,
3
0
0
4-H), 5.01–5.09 (m, 2H, 2-H, 3-H), 4.28 (t, 1H, J1 ,2 = 6.5 Hz,
CHNH), 4.08–4.11 (m, 1H, 6b-H), 3.96–4.01 (m, 1H, 6a-H), 3.78–
3
3.86 (m, 1H, 1-H), 3.67 (t, 1H, J5,6 = 6.9 Hz, 5-H), 2.65 (t,
3
0
0
J1 ,2 = 6.5 Hz, 2H, CH2CH@CH), 2.36 (s, 3H, CH3), 2.12 (s, 1H, NH),
1.27 (s, 9H, C(CH3)3), 1.20 (s, 18H, 2C(CH3)3), 1.09 (s, 9H,
C(CH3)3). 13C NMR (101 MHz, CDCl3): d = 193.45, 177.86, 177.68,
177.09, 176.86 (C@O), 153.52, 140.46, 138.24, 135.01, 129.30,
128.42, 127.54, 124.85 (Ph, CH@CH), 86.22, 71.73, 71.24, 68.71,
67.42, 61.78, 56.35 (C–O, C–N), 41.43, 39.06, 38.82, 38.71, 27.26,
27.21, 27.13, 27.08, 21.41, 21.10. ESIMS: [M+H]+ m/z 688.2. HRE-
SIMS: [M+Na]+ calcd for C38H57NO10Na+: 710.3875; found,
710.3878.
Compound 9b. white solid, mp 108–110 °C; ½a D25
ꢀ36.5° (c 1.0,
ꢃ
3
CHCl3). 1H NMR (400 MHz, DMSO): d = 6.87 (d, JH,H = 7.9 Hz, 2H,
3
Ph), 6.46 (d, 2H, JH,H = 7.9 Hz, Ph), 5.22 (s, 1H, NH), 4.22 (t,
3JH,H = 6.5 Hz, 1H, CHNH), 2.97–2.99 (m, 1H, COCH2), 2.36–2.42
(m, 1H, COCH2), 1.24–2.07 (m, 8H, 4CH2). 13C NMR (101 MHz,
CDCl3): d = 171.38, 138.56, 136.66, 128.45, 124.98, 56.49, 31.18,
30.25, 25.87, 20.04, 18.67. ESIMS: [M+Na]+ m/z 271.4. HRESIMS:
[M+Na]+ calcd for C13H16N2O3Na+: 271.1053; found, 271.1057.
3.3.14. (2E,6E)-Ethyl-5-[(2,3,4,6-tetra-O-pivaloyl-b-D-
galactopyranosyl)amino]-7-phenyl-hepta-2,6-dienal (5n)
Yield: 178 mg, 85%, white oil, Rf = 0.4 (petroleum ether/ethyl
acetate = 15:1). ½a D25
ꢃ
ꢀ21.6° (c 1.0, CHCl3). 1H NMR (400 MHz,
Acknowledgements
3
0
0
CDCl3): d = 9.38 (d, 1H, J4 ,5 = 7.5 Hz, CHO), 7.16–7.24 (m, 4H,
3
3
We thank the National Natural Science Foundation of China
(21072102), the Committee of Science and Technology of Tianjin
(11JCYBJC04200) and State Key Laboratory of Elemento-Organic
Chemistry in Nankai University for financial support.
0
0
0
0
Ph), 6.69 (dt, 1H, J3 ,4 = 16.2 Hz, J2 ,3 = 7.5 Hz, CH@CH), 6.42 (d,
3
3
0
0
0
0
1H, J6 ,7 = 15.9 Hz, CH@CH), 6.07 (dd, 1H, J3 ,4 = 16.2 Hz,
J4 ,5 = 7.5 Hz, CH@CH), 5.76 (dd, 1H, J6 ,7 = 15.9 Hz, J5 ,6 = 8.2 Hz,
3
3
3
0
0
0
0
0
0
CH@CH), 5.30 (s, 1H, 4-H), 4.98–5.05 (m, 2H, 2-H, 3-H), 4.95 (t, 1H,
3
0
0
J1 ,2 = 6.6 Hz, CHNH), 4.02–4.05 (m, 1H, 6b-H), 3.88–3.92 (m, 1H,
3
Supplementary data
0
0
6a-H), 3.75–3.80 (m, 2H, 1-H), 2.48 (t, J1 ,2 = 6.6 Hz, 2H,
CH2CH@CH), 1.84 (s, 1H, NH), 1.16 (s, 9H, C(CH3)3), 1.10 (s, 9H,
C(CH3)3), 1.09 (s, 9H, C(CH3)3), 1.00 (s, 9H, C(CH3)3). 13C NMR
(101 MHz, CDCl3): d = 193.81, 178.24, 178.03, 177.46, 177.26
(C@O), 153.70, 136.52, 135.62, 134.40, 129.97, 129.14, 128.45,
126.77 (Ph, CH@CH), 87.16, 72.17, 71.59, 69.04, 67.73, 62.07,
55.64 (C–O, C–N), 40.01, 39.46, 39.17, 39.12, 39.11, 27.60, 27.56,
27.55, 27.47. ESIMS: [M+H]+ m/z: 700.2. HRESIMS: [M+Na]+ calcd
for C39H57NO10Na+: 722.3875; found, 722.3876.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2013.03.
020.
References
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ꢃ
ꢀ22.7° (c 1.0, CHCl3). 1H NMR (400 MHz,
3
3
0
0
0
0
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(dt,
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3
5.41 (d, J3,4 = 2.9 Hz, 1H, 4-H), 5.15–5.19 (m, 1H, 2-H), 5.05–
5.09 (m, 1H, 3-H), 4.55–4.59 (m, 1H, CHNH), 4.00–4.06 (m, 2H,
6-H), 3.83–3.90 (m, 1H, 5-H, 1-H), 2.79–2.84 (m, 2H,
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