Total synthesis of caminoside B, a novel antimicrobial glycolipid isolated from the marine sponge Caminus sphaeroconia

Article abstract of DOI:10.1016/j.carres.2010.01.015

The first total synthesis of caminoside B, a novel marine antimicrobial glycolipid isolated from the marine sponge Caminus sphaeroconia, was developed. This marine small molecule inhibitor (IC₅₀ = 20 μM) targeting type III secretory pathway of

Full text of DOI:10.1016/j.carres.2010.01.015

Carbohydrate Research 345 (2010) 750–760
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Carbohydrate Research
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Total synthesis of caminoside B, a novel antimicrobial glycolipid isolated
from the marine sponge Caminus sphaeroconia
Zaihong Zhang a, Chengli Zong a, Gaopeng Song a, Guokai Lv a, Yuexing Chun a, Peng Wang a,
Ning Ding b, Yingxia Li b,
*
a School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
b School of Pharmacy, Fudan University, Shanghai 201203, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The first total synthesis of caminoside B, a novel marine antimicrobial glycolipid isolated from the marine
Received 14 October 2009
Received in revised form 21 January 2010
Accepted 25 January 2010
Available online 29 January 2010
sponge Caminus sphaeroconia, was developed. This marine small molecule inhibitor (IC50 = 20 lM) target-
ing type III secretory pathway of bacterial pathogenesis was assembled in good yield via a ‘2+2+1’ strat-
egy based on stereocontrolled construction of the four glycosidic linkages.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Caminoside B
Regioselective glycosylation
Antimicrobial glycolipid
Type III secretory pathway
1. Introduction
lose residue (sugar C), and L-quinovose (sugar D), which are rare in
nature, and an unprecedented aglycon in sponge glycolipids which
bears a C19 linear chain and a methyl ketone terminus. Thus, a total
synthesis of the first known caminoside A4a was initially achieved
by the Yu group,5 but there are still some aspects to improve in the
synthesis, for example, to stereoselectively construct the R-config-
ured secondary alcohol of the aglycon, to improve the synthetic
procedure, and to get the natural glycolipid instead of the perace-
tate derivative. In an effort to carry SAR studies and identify com-
pounds with improved activity, we now report a facile synthesis of
the fascinating compound caminoside B with an improved biolog-
ical activity as compared to A.
Knowledge of type III secretory pathway in various gram-nega-
tive organisms was accumulated in the late 1980s and early
1990s.1 This secretory system is found in disease-causing bacteria,
but not in their non-pathogenic counterparts. Notably, pathogens
use the type III secretory system to deliver different effectors that
influence host cells in a variety of ways.2 The virulence mechanism
of pathogens such as enteropathogenic Escherichia coli (EPEC) and
enterohemorragic E. coli 0157:H7 (EHEC) that are deadly toward
children and the elderly is mainly dependent on E. coli type III
secretion system, while benign commensal strains do not bear
such organization.3 So, components of this system might be good
targets for novel antimicrobial agents and selective type III secre-
tory system inhibitors are potential antimicrobials.
2. Results and discussion
Recently, a screening program aimed at discovering inhibitors
of the bacterial type III secretory system was developed. A bioas-
say-guided isolation of the methanol extract of the Caribbean
sponge Caminus sphaeroconia led to the discovery of caminosides
A to D, a new family of antimicrobial glycolipids, which are the first
As could be expected from the structural similarity between
caminosides A and B, the total synthesis of caminoside B presents
similar difficulties in that it requires considerable forethought in
the orchestration of the orthogonal protections of the carbohydrate.
Therefore, in our synthesis of caminoside B, besides utilizing the
advantages in total synthesis of caminoside A,5 we further optimized
thesyntheticroute. As outlinedin Scheme1, synthesisof caminoside
B was planned to be accomplished via a ‘2+2+1’ strategy. Building
block 2 as a glycosyl acceptor could result from the glycosylation
of (10R)-10-hydroxy-1-octadecane (6), in which the absolute
configuration at C-10 could be introduced via 2,3-O-isopropyli-
marine small molecule inhibitors (IC50 = 20 lM) targeting the type
III secretory pathway of bacterial pathogenesis and which show
reasonably potent in vitro inhibition of certain gram-positive
pathogens.4 Caminosides display a number of unique structural
features: a fully substituted glucose residue (sugar B), a 6-deoxyta-
dene-
D-glyceraldehyde and glucosyl donor 7. Building block 3,
* Corresponding author. Tel./fax: +86 21 51980127.
E-mail address: liyx417@fudan.edu.cn (Y. Li).
as a disaccharide donor, could be obtained by regioselective
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.01.015

Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
751
HO
6
O
OBn
OBn
O
O
BnO
BnO
O
BnO
BnO
CCl3
NH
O
OH
OH
OAc
2
7
O
O
O
HO
HO
A
OBn
OH
OH
O
O
STol
OLev
O
BnO
CCl3
NH
OBn
O
O
OH
O
C
9
O
HO
B
O
O
O
RO
BnO
OAzmb
HO
O
O
O
O
O
O
O
O
HO
OMP
OAzmb
3
O
O
O
D
HO
OH
8
HO
Caminoside A
R=Ac
CF3
NPh
Caminoside B (1) R=CH3(CH2)2CO
STol
OBn
O
O
BnO
BnO
OBn
or
BnO
BnO
4
5
Scheme 1. Retrosynthetic analysis of caminoside B.
glycosylation of 1-thiofucopyranoside 9 with a monosaccharide
acceptor 8 bearing two free hydroxyl groups at C-4 and C-6. The ste-
rically less hindered primary hydroxyl group at C-6 would be the
main glycosylation site. Then condensation of 2 and 3 could afford
the trisaccharide backbone. Lastly, coupling of the trisaccharide
acceptor with donors 4 and 5 could provide the tetrasaccharide
which could produce target compound 1 by hydrogenolysis of the
O-benzyl groups.
in 11 smoothly gave diol 12 (82%). Then selective tosylation of the
primary hydroxyl group in 12 was accomplished in a good yield
(97%) by using the method of Martinelli et al.7 involving Bu2SnO/
TsCl, and the tosylate was in turn converted into the epoxide 13
in an excellent yield (99%).8 The epoxide was opened to form the
(R)-alcohol 6 (81%) by reaction with the Grignard reagent prepared
from 8-bromo-1-octene.9 Reaction of 2-O-acetyl-3,4,6-tri-O-ben-
zyl-D
-glucose10 with CCl3CN and 1,8-diazabicyclo[5.4.0]undec-7-
in 99% yield. Then
Our study began with the preparation of the building block 2
which could be obtained by coupling of acceptor 6 with donor 7.
As outlined in Scheme 2, Wittig reaction of (S)-2,3-O-isopropyli-
ene (DBU) gave trichloroacetimidate
7
glycosylation of 7 with the acceptor 6 using TMSOTf as promoter
was carried out smoothly to give pure b-isomer 14 (JH-1,H-2
7.7 Hz) in 87% yield. To our delight, removal of the 2-O-acetyl
group (99%), followed by Wacker oxidation of the terminal C@C
double bond provided the methyl ketone 2 in 82% yield.4,11
The next effort was to construct disaccharide 3 (Scheme 5). For
this purpose, acceptor 8 was prepared from the known methoxy-
dene-D-glyceraldehyde with 1-octyltriphenylphosphonium bro-
mide gave the cis-alkene 10 in 86% yield.6 Reduction of the
unsaturated carbon–carbon bond was realized by a simple hetero-
geneous (Pd/C)-catalyzed hydrogenolysis to provide (R)-alcohol 11
in 91% yield. Acidic deprotection of the 1,2-O-isopropylidene group
Me
O
Me
O
Me
O
Me
Me
Me
a
HO
O
O
b
c
HO
O
CHO
R
S
R
12
R
10
11
O
d
e
f
6
7
R
OBn
g
h
13
O
O
OBn
O
BnO
BnO
BnO
BnO
OAc
OH
14
OAc
16
OBn
i
O
O
2
BnO
BnO
OH
15
Scheme 2. Reagents and conditions: (a) BuLi, Ph3P+(CH2)7CH3Brꢀ, THF, 86%; (b) H2, Pd–C, EtOH, 91%; (c) PPTs, MeOH, 82%; (d) (i) Bu2SnO, TEA, p-TsCl, CH2Cl2, 97%; (ii) KOH,
PhCH3, 99%; (e) 8-bromo-1-octylene, magnesium, I2, Cu2Br2, THF, 81%; (f) CCl3CN, DBU, CH2Cl2, 99%; (g) TMSOTf, 4 Å MS, CH2Cl2, 87%; (h) MeONa, MeOH, 99%; (i) PdCl2,
Cu(OAc)2, O2 (1 atm), DMA–H2O, 82%.

752
Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
O
O
Ph
O
O
Ph
O
O
O
OMP
O
OMP
OAzmb
O
O
OH
18
20
8
O
Ph
O
O
a
OMP
c
b
HO
OH
17
HO
HO
AzmbO
O
Ph
O
Ph
O
O
O
O
O
OMP
O
OMP
O
O
O
OMP
O
HO
AzmbO
O
19
22
21
Scheme 3. Reagents and conditions: (a) n-Butyryl chloride, CuCl2, NaH, THF, 79%; (b) AzmbOH, DMAP, EDCꢁHCl, CH2Cl2, 96%; (c) 80% HOAc, 47% for 8, 38% for 22.
phenyl glucoside 1712 in three steps (Scheme 3). Regioselective pro-
tection of the C-3 hydroxyl group of 4,6-O-benzylidene-b- -glyco-
pletely supported by its subsequent reaction product, the C-4 bu-
tyryl derivative 27. Peaks at d 5.02 ppm (t, 1H, J 9.9 Hz, H-4) and
3.85 ppm (d, 1H, J 9.9 Hz, H-6a), 3.66 ppm (dd, 1H, J 11.0, 8.3 Hz,
H-6b) in the 1H NMR spectrum of 27, in comparison to those for
26 at 3.51–3.47 ppm (m, 1H, H-4), 3.98 ppm (d, 1H, J 11.0 Hz, H-
6a), and 3.86 ppm (d, 1H, J 2.2 Hz, H-6b), confirmed the (1?6)-
linkage in its precursor 26. Then, selective removal of the levuli-
noyl group with hydrazine acetate without destroying the Azmb
and butanoyl groups proceeded smoothly to give compound 28
in 85% yield. Net inversion at C-2 from the equatorial 2-OH to
the axial one can be accomplished successfully by oxidation to a
2-keto-b-galactoside followed by stereoselective reduction to the
2b-alcohol 29 in 96% yield in two steps (no equatorial isomer
was detected in the reduction step).5,16 The stereoselectivity of
the reduction was further evidenced by the signal for H-10 in the
1H NMR spectrum which appeared as a singlet at d 4.26 ppm. Final-
ly, oxidative removal of the anomeric methoxyphenyl group with
ammonium cerium(IV) nitrate in wet methyl cyanide (5:1
MeCN–water), followed by treatment with CCl3CN and DBU gave
the disaccharide trichloroacetimidate 3 in 87% yield in two steps.
With the required building blocks 2 and 3 in hand, a TMSOTf-
promoted selective coupling of these entities was carried out to af-
D
pyranosides with a butyryl group could be proved to be a
challenging task because the butanoyl substituent must be kept in
the target compound 1 and the C-2 hydroxyl must also be protected
by a participating group in order to control formation of the b-glyco-
sidic linkage in the subsequent glycosylation step. Using the same
procedure as reported by Osborn’s group13, however, a mixture of
C-2- and C-3-protected products (79%) was obtained after scaling
up the reaction to one gram. Furthermore, chromatography was
found useless as 18 and 19 have the same Rf-values. The mixture of
compounds were then coupled with 2-(azidomethyl)benzoic acid
(AzmbOH) in the presence of EDCꢁHCl and 4-N,N-dimethylamino-
pyridine (DMAP) to afford a mixture of 20 and 21 in 96% yield, which
have also the same Rf-values.14 Removal of the 4,6-O-benzylidene
group in 20/21 (80% AcOH, 80 °C) produced diols 8 (47%) and 22
(38%) in a pure form after chromatographic purification. Donor 9
(Scheme 4) was prepared from acetobromofucose 23, which was
readily obtained by C-6 deoxygenation of D
-galactose in five steps.15
Conversion of 23 into 25 was achieved through a one-pot sequence
of anomeric bromination, halide-promoted orthoesterification,
deacetylation, benzylation, acid-catalyzed ring opening, and then
acylationto affordan anomericmixture of 24and 24a. This anomeric
mixture was directly converted into the corresponding thioglyco-
side 25 in a satisfactory yield (74% overall yield for six steps).10 Sub-
sequently, the C-2 acetyl group of 25 was removed by Zemplén
deacetylation, followed by protection of the corresponding C-2 posi-
tion with a levulinoyl group providing the donor 9 in an excellent
yield in two steps (99%).
ford b-D-Tal-(1?6)-b-D-Glc-(1?2)-b-D-Glc-trisaccharide 30 in 76%
0
0
yield (JH-1 ,H-2 7.4 Hz). No glycosylation took place on the free axial
2-OH of the talose moiety. This selectivity can be explained by the
fact that the equatorial 2-OH of a glucoside is less hindered than
the axial 2-OH of a taloside and that the presence of the hydrogen
bond between the axial 2-OH and the axial 4-OBn of the taloside
residue could reduce the reactivity at O-2. Thus, the glucoside
2-OH of block 2 and disaccharide trichloroacetimidate may be
more in line with the ‘matching’ acceptor and donor reactivities.
Then, exhaustive benzylation of 30 (10 equiv of BnOC(@NH)CCl3,
catalytic TfOH, 1:1 CH2Cl2–cyclohexane, 1 h, 79%)17 followed by
Regioselective glycosylation of acceptor 8 and donor 9 in the
presence of NIS and AgOTf as promoter was carried out smoothly
to afford the b-
D-Fuc-(1?6)-b-D-Glc-disaccharide 26 (86%) with
complete C-6 selectivity (Scheme 5). The regioselectivity was com-
OBn
O
OBn
OAc
OAc
OAc
BnO
O
OAc
a
O
O
24
OBn
b
BnO
AcO
AcO
O
AcO
23
O
O
Br
O
O
Me
Me
OEt
OEt
BnO
AcO
24-a
OAc
OBn
O
c
STol
BnO
9
OAc
25
Scheme 4. Reagents and conditions: (a) (i) TBAI, CH3CN, CH3C(OEt)3; (ii) MeONa, MeOH, rt; (iii) BnBr, NaH, DMF; (iv) 1 M HCl; (v) Ac2O, pyridine; (b) p-TolSH, BF3ꢁEt2O, 74%
for six steps; (c) (i) MeOH, MeONa; (ii) levulinic acid, EDCꢁHCl, DMAP, CH2Cl2, 99% for two steps.

Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
753
deprotection of the C-2 azidomethylbenzoyl group of 31 provided
the trisaccharide acceptor 32 (85%).5,14
O-benzyl-protecting groups over Pd/C did not meet any difficulty
providing the target caminoside B (1) in 88% yield. The physical
data obtained were in full agreement with those reported for the
natural product.4b
In conclusion, a facile synthesis of the marine antimicrobial gly-
colipidcaminosideB wasachievedsuccessfullyviaa ‘2+2+1’strategy
based on the stereocontrolled construction of the four glycosidic
linkages. With donors equipped with appropriate neighboring par-
ticipating groups, the 1,2-trans b-glucopyranoside linkage was
formed conveniently. Under the influence of the anomeric effect
and with a donor bearing a non-participating 2-O-Bn group, the
1,2-cis a-quinovopyranoside was obtained easily, while the 1,2-cis
b-mannopyranoside-type linkage of the 6-deoxy-talose moiety,
the most challenging work of the total synthesis, was installed by
stereoselective elaboration at position 2 of 6-deoxy-b-D-galactopy-
ranoside. The major novelty of our work, with respect to the previ-
ously reported caminoside A, is that the R-configured secondary
alcohol of the aglycon has been stereoselectively constructed. Fur-
thermore, we got the pure targeted natural isomer caminoside B, in-
stead of the peracetate derivative, which could not allow access to
the natural glycolipid since the acetyl group cannot be selectively
Two monosaccharide donors 4 and 5 were designed for the
investigation of the later coupling of trisaccharide 32 and quino-
vose donor. The preparation of 4 (Scheme 6) started with the
6-deoxy-1-thio-b-L
-glucoside perbenzoate 33,18 treatment with
BF3ꢁEt2O and p-TolSH to afford thioglycoside 34 (63%), and MeO-
Na-induced elimination of Bz and benzylation which smoothly
gave the desired donor 4 in a satisfactory overall yield (59% in
two steps). Hydrolysis of 4 with N-bromosuccinimide (NBS) in
wet acetone (9:1 acetone–water) gave compound 35 in 94% yield,
which can be transformed into trifluoroacetimidate 5 by treatment
with CF3C(Cl)@NPh and K2CO3.5 When 2.0 equiv of thioglycoside
donors 4 was employed in the presence of NIS-AgOTf in CH2Cl2,
tetrasaccharide 36 was obtained in a poor yield as outlined in
Scheme 7 (23%). However, coupling of the newly prepared perben-
zyl L-quinovosyl trifluoroacetimidate 5 and 32 in the presence of
TMSOTf as reported by Yu and co-workers5 gave 36 in a moderate
yield (39%). The stereochemistry of the newly formed glycosidic
linkage was determined to be the desired a
-form by 1H NMR spec-
000, H-2000
troscopy (JH-1
3.3 Hz). Finally, catalytic hydrogenation of the
OBn
O
OBn
O
O
BnO
O
BnO
LevO
b
a
LevO
8
9
O
+
HO
O
O
O
OMP
OAzmb
O
OMP
OAzmb
O
O
O
26
27
c
OH
O
OBn
BnO
OBn
BnO
OBn
OH
O
O
O
O
O
BnO
O
HO
O
O
O
O
O
d
OMP
OAzmb
O
e
O
O
NH
CCl3
O
OMP
OAzmb
O
O
O
O
AzmbO
O
O
29
28
3
O
O
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
f
O
O
g
2
O
O
O
O
BnO
HO
O
O
BnO
BnO
BnO
OR
OAzmb
O
O
O
O
BnO
O
O
O
O
30
31 R=Azmb
32 R=H
h
Scheme 5. Reagents and conditions: (a) NIS, AgOTf, 4 Å MS, CH3CN–CH2Cl2, 0 °C to rt, 86%; (b) n-Butyryl chloride, pyridine, 88%; (c)H2NNH2ꢁHOAc, MeOH–CH2Cl2, 85%; (d) (i)
Dess–Martin periodinane, CH2Cl2, rt; (ii) NaBH4, CH2Cl2–CH3OH, 96% for two steps; (e) (i) CAN, CH3CN–H2O; (ii) CCl3CN, DBU, CH2Cl2, 87% for two steps; (f) TMSOTf, 4 Å MS,
CH2Cl2, 76%; (g) BnOC(@NH)CCl3, TfOH, 4 Å MS, CH2Cl2–cyclohexane, 79%; (h) Bu3P, THF–H2O, 85%.
OH
OBz
OBz
O
STol
OBz
a
O
BzO
O
c
BzO
b
d
BnO
5
4
OBn
BzO
BzO
BnO
35
34
33
Scheme 6. Reagents and conditions: (a) BF3ꢁEt2O, TolSH, CH2Cl2, 63%; (b) (i) MeONa, MeOH; (ii) BnBr, NaH, TBAI, DMF, 59% for two steps; (c) NBS, acetone–H2O, 94%; (d)
CF3C(Cl)@NPh, K2CO3, acetone, rt, 90%.

754
Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
O
O
OBn
OBn
O
O
O
BnO
BnO
O
BnO
BnO
O
O
O
O
O
BnO
O
BnO
O
a
BnO
O
b
BnO
OH
1
4 or 5
O
O
O
BnO
O
O
BnO
O
O
O
O
O
BnO
32
OBn
BnO
36
Scheme 7. Reagents and conditions: (a) NIS, AgOTf, 4 Å MS, CH2Cl2–Et2O, 0 °C to rt, 23% for 4 as donor; TMSOTf, 4 Å MS, Et2O, 0 °C to rt, 39% for 5 as donor; (b) Pd/C, EtOH–
EtOAc, 50 °C, 88%.
removed in the presence of a butanoyl group. This result should pro-
vide a practical approach to other analogues of caminoside B, which
are useful substrates for biological examinations in the type III secre-
tory inhibitor domain.
for 24 h at room temperature under H2 atmosphere, the mixture
was filtered through a Celite pad and the filtrate was concen-
trated. The resulting residue was subjected to column chroma-
tography (25:1 petroleum ether–EtOAc) to yield 11 (777.5 mg,
91%) as a colorless oil: Rf 0.65 (25:1 petroleum ether–EtOAc);
½
a 2D2
ꢂ
ꢀ36.9 (c 0.07, CHCl3); 1H NMR (600 MHz, CDCl3): d 4.10–
3. Experimental section
3.1. General methods
4.02 (m, 2H, OCHH), 3.50 (t, 1H, J 7.3 Hz, OCH), 1.67–1.62 (m,
1H, OCH2CHH), 1.51–1.46 (m, 1H, OCH2CHH), 1.41 (s, 3H, Me),
1.36 (s, 3H, Me), 1.33–1.27 (m, 2H, OCH2CH2CHH), 1.26 (br s,
12H, 6 ꢃ CH2), 0.88 (t, 3H, J 6.9 Hz, CH3); 13C NMR (150 MHz,
CDCl3): d 108.5, 76.2, 69.5. 33.6, 31.9, 29.7–29.4. 22.7, 14.1.
Solvents were purified in a conventional manner. Thin layer
chromatography (TLC) was performed on precoated E. Merck Silica
Gel 60 F254 plates. Flash column chromatography was performed
on silica gel (200–300 mesh, Qingdao, China). Optical rotations
were determined with a Perkin–Elmer Model 241 MC polarimeter.
1H and 13C NMR spectra were taken on a JEOL JNM-ECP 500 or 600
spectrometer with tetramethylsilane as the internal standard, and
chemical shifts are recorded in d values. Mass spectra were re-
corded on a Q-TOF Ultima Global mass spectrometer in a positive
ion mode.
3.4. (R)-Undecane-1,2-diol (12)
To a solution of 11 (134.0 mg, 0.6 mmol) in MeOH (10 mL) was
added pyridinium p-toluenesulfonate (45.2 mg, 10% w/w) at ambi-
ent temperature under N2. The reaction mixture was stirred for
12 h until completion as judged by TLC. Then the mixture was con-
centrated and purified by silica gel column chromatography (1:1
petroleum ether–EtOAc) to give diol 12 (90.3 mg, 82%) as a white
solid: Rf 0.45 (1:1 petroleum ether–EtOAc); ½a D22
ꢂ
+5.8 (c 0.06,
CHCl3); 1H NMR (600 MHz, CDCl3): d 3.71 (br s, 1H, OCHH), 3.66
(d, 1H, J 11.0 Hz, OCHH), 3.44(t, 1H, J 9.2, 8.7 Hz, OCH), 2.32 (br s,
2H, 2 ꢃ OH), 1.45–1.41 (m, 2H, OCH2CHH), 1.31–1.28 (m, 2H,
OCH2CH2CHH), 1.26 (br s, 12H, 6 ꢃ CH2), 0.88 (t, 3H, J 7.1 Hz,
CH3); 13C NMR (150 MHz, CDCl3): d 72.3, 66.8, 33.2, 31.9, 29.6–
29.3, 25.5, 22.6, 14.1.
3.2. (R, E)-2,2-Dimethyl-4-(non-1-enyl)-1,3-dioxolane (10)
Octyl triphenylphosphonium bromide (20.0 g, 44.0 mmol) was
suspended in dry THF (300 mL). The mixture was cooled to 0 °C
and n-BuLi (14.4 mL, 23.0 mmol) (1.6 M in hexane) was added drop-
wise. The red solution was stirred for 30 min, and then (S)-2,3-O-iso-
propylidene-D-glyceraldehyde (1.5 g, 11.5 mmol) in THF (6 mL) was
added slowly. The reaction mixture was allowed to warm to room
temperature while stirred overnight and was monitored by TLC.
For workup, the reaction mixture was quenched with 10 mL MeOH.
Afterward 80% MeOH in water was added and the reaction mixture
was extracted with hexane. The combined hexane layers were dried
over Na2SO4 and evaporated. The resulting residue was subjected to
column chromatography (50:1, petroleum ether–EtOAc) to yield
compound 10 as a colorless oil (2.23 g, 86%): Rf 0.65 (20:1 petroleum
3.5. (R)-1,2-Nonyloxirane(13)
To a solution of diol 12 (1.0 g, 5.4 mmol), dibutyltin oxide
(134.9 mg, 0.5 mmol), and triethylamine (1.5 mL, 10.8 mmol) in
CH2Cl2 (50 mL) was added p-toluenesulfonyl chloride (1.5 g,
8.1 mmol) in one portion. The reaction mixture was stirred at ambi-
enttemperature for16 handthen thereactionwasquenchedwithaq
saturated NaHCO3 (50 mL) and the reaction mixture was extracted
with EtOAc (2 ꢃ 100 mL). The EtOAc layer was washed with brine
(2 ꢃ 100 mL), dried over MgSO4, filtered, and concentrated under
diminished pressure. The residue was purified by silica gel column
chromatography (10:1 petroleum ether–EtOAc) to give the tosylate
(1.8 g, 97%) as a white solid; Rf 0.50 (4:1 petroleum ether–EtOAc);
ether–EtOAc); ½a D22
ꢂ
ꢀ6.9 (c 0.17, CHCl3); 1H NMR (600 MHz, CDCl3):d
5.63 (dt, 1H, J 13.0, 7.8 Hz, @CH), 5.40 (dd, 1H, J 11.0, 8.7 Hz, @CH),
4.87–4.83 (m, 1H, CHO), 4.06 (dd, 1H, J 7.8, 6.0 Hz, OCHH), 3.51 (t,
1H, J 8.3 Hz, OCHH), 2.15–2.02 (m, 2H, @CHCHH), 1.43, 1.40 (2s,
6H, 2 ꢃ Me), 1.31–1.27 (m, 2H, @CHCH2CHH), 1.25 (br s, 8H,
4 ꢃ CH2), 0.88 (t, 3H, J 6.9 Hz, CH3). 13C NMR (125 MHz, CDCl3): d
133.6, 130.0, 114.0, 76.2, 69.5, 33.8, 31.9, 29.7–29.3, 22.7, 14.1.
½
a 2D2
ꢂ
ꢀ6.2 (c 0.06, CHCl3); 1H NMR (600 MHz, DMSO-d6): d 7.79 (d,
2H, J 8.3 Hz, Ph), 7.48 (d, 2H, J 6.7 Hz, Ph), 4.97 (br s, 1H, OH), 2.91–
2.89 (m, 1 H, OCH), 3.85 (dd, 1H, J 9.7, 4.1 Hz, OCHH), 3.80 (dd, 1H, J
10.1, 5.9 Hz, OCHH), 3.57–3.54 (m, 1H, OCH), 2.42 (s, 3H, PhCH3),
1.31–1.23 (m, 2H, OCHCHH), 1.20 (br s, 14H, 7 ꢃ CH2), 0.85 (t, 3H, J
7.1 Hz, CH3); 13C NMR (150 MHz, CDCl3): d 145.0, 132.6, 129.9,
127.9, 74.0, 69.5, 32.6, 31.8, 29.5–29.2, 25.2, 22.6, 21.6, 14.1.
3.3. (R)-2,2-Dimethyl-4-nonyl-1,3-dioxolane (11)
Compound 10 (845.5 mg, 3.7 mol) was dissolved in MeOH
(50 mL) and then 10%-Pd/C (500 mg) was added. After stirring

Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
755
To a solution of the monotosyl compound (0.3 g, 0.9 mmol) in
PhCH3 (10 ml), powdered KOH (59 mg, 1.0 mmol) was added and
the suspension was stirred under N2 for 45 min till the starting
material was not detectable on TLC (20:1 petroleum ether–EtOAc).
The reaction mixture was then filtered and concentrated. The res-
idue was purified by silica gel column chromatography (50:1
petroleum ether–EtOAc) to give compound 13 (148.9 mg, 99%) as
mixture was stirred under these conditions for 30 min and then
neutralized with Et3N. The solid was filtered off, and the filtrate
was concentrated under diminished pressure. The resulting resi-
due was purified by silica gel column chromatography (50:1 petro-
leum ether–EtOAc) to give 14 (138.8 mg, 87%) as a syrup: Rf 0.39
(15:1 petroleum ether–EtOAc); ½a D22
ꢂ
ꢀ11.4 (c 0.06, CHCl3); 1H
NMR (600 MHz, CDCl3): d 7.33–7.19 (m, 15H, Ph), 5.83–5.76 (m,
1H, @CH), 4.99–4.91 (m, 3H, @CHH and H-2), 4.79 (d, 2H, J
11.4 Hz, PhCHH), 4.66 (d, 1H, J 11.4 Hz, PhCHH), 4.64 (d, 1H, J
12.0 Hz, PhCHH), 4.59 (d, 1H, J 10.8 Hz, PhCHH), 4.56 (d, 1H, J
12.0 Hz, PhCHH), 4.36 (d, 1H, J 7.8 Hz, H-1), 3.72–3.64 (m, 4H, H-
3, H-4, H-5 and H-6a), 3.51 (dd, 1H, J 12.0, 6.0 Hz, H-6b), 3.47–
3.44 (m, 1H, CHO), 2.03–1.99 (m, 2H, @CHCHH), 1.99 (s, 3H,
COCH3), 1.56 (br s, 10H, (CH2)5), 1.42–1.40 (m, 2H, CHHCHO),
1.34–1.29 (m, 2H, CHOCHH), 1.25(br s, 14H, (CH2)7), 0.88 (t, 3H,
J = 6.9 Hz, CH3); 13C NMR (150 MHz, CDCl3): d 169.4, 139.2, 138.3,
138.2, 137.9, 128.4, 128.3, 128.1, 127.8, 127.7, 127.6, 127.5,
114.15, 114.0, 100.8, 83.1, 80.8, 78.1, 75.2, 75.0, 74.9, 73.6, 73.5,
69.0, 34.9, 34.1, 33.8, 31.9, 29.9–28.9, 25.3, 25.0, 22.7, 20.9, 14.1;
ESIMS: calcd for [M+Na]+ m/z 779.5; found: 779.5.
a colorless oil: Rf 0.70 (30:1 petroleum ether–EtOAc); ½a D22
ꢂ
+8.6 (c
0.09, CHCl3); 1H NMR (600 MHz, CDCl3): d 2.91–2.89 (m, 1 H,
OCH), 2.75 (dd, 1H, J 4.7, 4.0 Hz, OCHH), 2.46 (dd, 1H, J 4.8,
2.6 Hz, OCHH), 1.54–1.51 (m, 2H, OCHCHH), 1.48–1.39 (m, 2H,
OCHCH2CHH), 1.27 (br s, 12H, 6 ꢃ CH2), 0.85 (t, 3H, J 6.9 Hz,
CH3); 13C NMR (150 MHz, CDCl3): d 52.4, 47.1, 32.5, 31.9, 29.5–
29.3, 25.9, 22.7, 14.1.
3.6. (R)-Nonadec-1-en-10-ol (6)
A
solution of 8-bromo-1-octylene (250 lL, 1.5 mmol) was
added dropwise to a suspension of magnesium turnings (50 mg,
2.0 mmol) and a catalytic amount of I2 in Et2O (10 mL) under N2.
The mixture was refluxed for 2 h, then cooled to room tempera-
ture, and added dropwise to a stirred solution of purified copper io-
dide (33.6 mg, 0.2 mmol) in dry THF (5 mL) at ꢀ20 °C. After 10 min,
a solution of 13 (60 mg, 0.35 mmol) in THF (2 mL) was added drop-
wise. Then the mixture was stirred at 0 °C for an additional 30 min
while warming to room temperature. The product was extracted
with EtOAc (3 ꢃ 50 mL). The combined organic layers were washed
with brine (50 mL), dried, and evaporated. The residue was purified
by silica gel column chromatography (80:1 petroleum ether–
EtOAc) to give compound 6 (80.3 mg, 81%) as a white solid: Rf
3.9. (10R)-Nonadec-1-en-10-yl 3,4,6-tri-O-benzyl-b-D-
glucopyranoside (15)
To a solution of compound 14 (337.0 mg, 0.4 mmol) in dry
MeOH (5 mL) and CH2Cl2 (5 mL) was added NaOMe until pH 8.5.
The reaction mixture was stirred at 35 °C for 30 h, after which
the reaction mixture was neutralized with Dowex 50 ꢃ 8(H+) resin
until pH 7.0, filtered, and concentrated. The residue was purified by
silica gel column chromatography (50:1 petroleum ether–EtOAc)
to give 15 (318.0 mg, 99%) as a white solid: Rf 0.39 (20:1 petroleum
0.40 (15:1 petroleum ether–EtOAc); ½a D22
ꢂ
ꢀ1.5 (c 0.11, CHCl3); 1H
NMR (600 MHz, DMSO-d6): d 5.82–5.75 (m, 1H, @CH), 5.01–4.97
(m, 1H, @CHH), 4.94–4.92 (m, 1H, @CHH), 4.19 (d, 1H, J 5.4 Hz,
OH), 3.32 (br s, 1H, CH), 2.01–1.98 (m, 2H, @CHCH2), 2.01–1.98
(m, 2H, @CHCH2), 1.24 (br s, 28H, 14 ꢃ CH2), 0.85 (t, 3 H, J 7.2 Hz,
CH3); 13C NMR (150 MHz, CDCl3): d 139.2, 114.1, 72.0, 37.5, 33.8,
31.9, 29.7–28.9, 25.6, 22.7, 14.1.
ether–EtOAc); ½a D22
ꢂ
ꢀ9.3 (c 0.3, CHCl3); 1H NMR (600 MHz, CDCl3):
d 7.39–7.20 (m, 15H, Ph), 5.83–5.77 (m, 1H, @CH), 5.00–4.97 (m,
1H, @CHH), 4.96 (d, 1H, J 11.0 Hz, PhCHH), 4.94–4.91 (m, 1H,
@CHH), 4.84 (d, 1H, J 11.0 Hz, PhCHH), 4.83 (d, 1H, J 11.6 Hz,
PhCHH), 4.62 (d, 1H, J 12.7 Hz, PhCHH), 4.58 (d, 1H, J 9.4 Hz,
PhCHH), 4.56 (d, 1H, J 12.1 Hz, PhCHH), 4.28 (d, 1H, J 7.7 Hz, H-
1), 3.73 (dd, 1H, J 11.0, 2.2 Hz, H-6a), 3.70 (dd, 1H, J 11.0, 4.4 Hz,
H-6b), 3.66–3.62 (m, 1H, OCH), 3.61–3.52 (m, 3H, H-3, H-4 and
H-2), 3.48–3.45 (m, 1H, H-5), 2.34–2.18 (m, 2H, @CHCHH), 2.06–
2.00 (m, 2H, OCHCHH), 1.68–1.21 (m, 26H, 13 ꢃ CH2), 0.88 (t, 3H,
J 6.9 Hz, CH3); 13C NMR (150 MHz, CDCl3): d 139.2, 138.7, 138.3,
138.1, 129.7–127.6, 114.1, 114.0, 102.0, 84.7, 80.1, 75.2, 75.0,
73.6, 69.1, 34.8, 34.1, 33.8, 31.9, 29.7–28.9, 25.2, 22.7, 14.1.
3.7. 2-O-Acetyl-3,4,6-tri-O-benzyl-a-D-glucopyranosyl
trichloroacetimidate (7)
To a stirred solution of 2-O-acetyl-3,4,6-tri-O-benzyl-
16 (5.0 g, 10.0 mmol) and CCl3CN (6.2 mL, 60.9 mmol) in CH2Cl2
(100 mL) at 0 °C was added DBU (780 L, 5.0 mmol). After 2 h,
D-glucose
l
the solution was concentrated and the residue was purified by sil-
ica gel column chromatography (10:1 petroleum ether–EtOAc) to
afford 7 (6.4 g, 99%) as a syrup: Rf 0.52 (6:1 petroleum ether–
3.10. (10R)-2-Nonadecanone-10-yl 3,4,6-tri-O-benzyl-b-D-
glucopyranoside (2)
EtOAc); ½a 2D0
ꢂ
+120.8 (c 0.13, CHCl3); 1H NMR (600 MHz, CDCl3): d
8.56 (s, 1H, NH), 7.33–7.16 (m, 15 H, Ph), 6.52 (d, 1H, J 3.7 Hz, H-
1), 5.07 (dd, 1H, J 9.9, 3.7 Hz, H-2), 4.86 (d, 1H, J 11.8 Hz, PhCHH),
4.83 (d, 1H, J 10.6 Hz, PhCHH), 4.77 (d, 1H, J 11.3 Hz, PhCHH),
4.63 (d, 1H, J 12.1 Hz, PhCHH), 4.57 (d, 1H, J 10.6 Hz, PhCHH),
4.50 (d, 1H, J 12.1 Hz, PhCHH), 4.09 (t, 1H, J 9.7 Hz, H-3), 4.02–
3.99 (m, 1H, H-5), 3.88 (t, 1H, J 9.5 Hz, H-4), 3.81 (dd, 1H, J 11.0,
3.3 Hz, H-6a), 3.69 (dd, 1H, J 11.0, 1.9 Hz, H-6b), 1.93 (s, 3H,
COCH3); 13C NMR (150 MHz, CDCl3): d 170.0, 163.4, 160.9, 138.2,
137.7, 128.4–127.6, 93.9, 79.4, 75.4, 75.3, 73.4, 73.3, 72.3, 67.8,
60.3, 20.5, 14.1. ESIMS: calcd for [MꢀCCl3CN+Na]+ m/z 515.2;
found: 515.2.
To a mixture of 15 (277.8 mg, 0.4 mmol) in N,N-dimethylacet-
amide (3 mL) and water (0.3 mL), PdCl2 (18.6 mg, 0.1 mmol) and
Cu(OAc)2ꢁH2O (155.7 mg, 0.8 mmol) were added. The mixture
was stirred at 50 °C under oxygen for 7 h until the reaction was
complete as judged by TLC. Then it was diluted with CH2Cl2
(100 mL), washed with saturated aq NaHCO3 (2 ꢃ 50 mL), water
(50 mL), and brine (2 ꢃ 50 mL), dried over Na2SO4, and concen-
trated. The residue was purified by silica gel column chromatogra-
phy (10:1 petroleum ether–EtOAc) to give 2 (233.3 mg, 82%) as a
syrup: Rf 0.31 (6:1 petroleum ether–EtOAc); ½a D22
ꢀ11.8 (c 0.1,
ꢂ
CHCl3); 1H NMR (600 MHz, CDCl3): d 7.38–7.19 (m, 15H, Ph),
4.95 (d, 1H, J 11.5 Hz, PhCHH), 4.84 (d, 1H, J 11.0 Hz, PhCHH),
4.83 (d, 1H, J 11.0 Hz, PhCHH), 4.62 (d, 1H, J 12.4 Hz, PhCHH),
4.57 (d, 1H, J 10.5 Hz, PhCHH), 4.55 (d, 1H, J 11.9 Hz, PhCHH),
4.28 (d, 1H, J 7.8 Hz, H-1), 3.72 (dd, 1H, J 11.0, 2.3 Hz, H-6a), 3.70
(dd, 1H, J 11.0, 4.1 Hz, H-6b), 3.65–3.61 (m, 1H, OCH), 3.60–3.57
(m, 2H, H-3 and H-4), 3.53 (t, 1H, J 9.1 Hz, H-2), 3.48–3.45 (m,
1H, H-5), 2.37 (t, 2H, J 7.32 Hz, COCHH), 2.11 (s, 3H, COCH3),
3.8. (10R)-Nonadec-1-en-10-yl 2-O-acetyl–3,4,6-tri-O-benzyl-b-
D
-glucopyranoside (14)
To
0.21 mmol), and 4 Å molecular sieves in dry CH2Cl2 (5 mL), TMSOTf
(5
L, 0.03 mmol) was added at ꢀ20 °C under argon. The reaction
a mixture of 7 (236.9 mg, 0.37 mmol), 6 (60.0 mg,
l

756
Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
1.58–1.26 (m, 28 H, 14 ꢃ CH2), 0.88 (t, 3H, J 6.9 Hz, CH3); 13C NMR
(150 MHz, CDCl3): d 138.8, 138.4, 138.3, 128.4–127.5, 102.0, 84.7,
79.9, 77.7, 75.3–75.0, 73.6, 69.3, 43.8, 34.8, 34.1, 31.9, 29.8–29.2,
25.3, 25.2, 23.9, 22.7, 14.1; ESIMS: calcd for [M+Na]+ m/z 753.5;
found: 753.6.
H-3), 5.32 (d, 1H, J 8.2 Hz, H-1), 5.07 (dd, 1H, J 9.3, 8.8 Hz, H-2),
4.80 (d, 1H, J 13.7 Hz, PhCH2), 4.80 (t, 1H, J 5.5 Hz, 6-OH), 4.69 (d,
1H, J 13.7 Hz, PhCH2), 3.76–3.73 (m, 1H, H-4), 3.71 (s, 3H, OMe),
3.70–3.64 (m, 2H, H-6), 3.59–3.55 (m, 1H, H-5), 2.25–2.14 (m,
2H, COCH2), 1.45–1.40 (m, 2H, CH2CH3), 0.71 (t, 3H, J = 7.7 Hz,
CH3); 13C NMR (150 MHz, DMSO-d6): d 171.7, 163.4, 154.7, 150.7,
136.3, 132.8, 130.6, 130.4, 128.9, 128.4, 117.7, 114.5, 98.5, 76.5,
76.0, 71.2, 67.5, 60.0, 55.3, 51.7, 35.2, 17.8, 13.0; ESIMS: calcd for
[M+Na]+ m/z 538.2; found: 538.2.
3.11. 4-Methoxyphenyl 2-O-[2-(azidomethyl)benzoyl]-3-O-
butyryl-b-
D-glucopyranoside (8)
4-Methoxyphenyl 4,6-O-benzylidene-b-
D
-glucopyranoside (250
mg, 0.67 mmol) was dissolved in anhyd THF (25 mL THF) and NaH
(83.2 mg, 1.9 mmol) was added. The formation of the disodium alco-
holate was complete in 1 h at room temperature to give a thick white
slurry. Anhydrous copper(II) chloride (88.4 mg, 0.67 mmol) was
added to the alcoholate slurry which went to dissolution as a dark
greensolution. Tothegreenchelatesolutionwasaddedbutyrylchlo-
3.13. p-Tolyl 3,4-di-O-benzyl-2-O-acetyl-1-thio-b-D-
fucopyranoside (25)
To a suspension of acetobromofucose 23 (3 g, 8.8 mmol) in dry
MeCN (50 mL), triethylorthoacetate (3.0 mL, 17.6 mmol) was
added, followed by the addition of tetrabutylammonium iodide
(1.6 g, 4.4 mmol). The mixture was allowed to stir for 12 h. When
the reaction was complete (TLC 3:1 petroleum ether–EtOAc),
Et3N was added to neutralize the solution and the mixture was
evaporated to dryness.
To a dry methanolic solution (25 mL) of the residue was added
NaOMe at 0 °C until pH 8.5. The reaction mixture was stirred at
room temperature for 30 min, after which the reaction mixture
was concentrated. The residue was dried under diminished pres-
sure to give a crude product.
ride (83.0 lL, 0.8 mmol) and the reaction mixture was left to stir un-
der N2 for 5 h. To the solution were added water (3 mL) and 3% aq
NH3 (3 mL) to give a dark blue solution. The organic layer was sepa-
rated and the water layer was extracted with EtOAc (5 ꢃ 50 mL). The
organic fractions were combined, dried with MgSO4, and the excess
solvent was removed under diminished pressure to yield a pale yel-
low oil which when subjected to column chromatography (8:1
petroleum ether–EtOAc) yielded the mixture of 18 and 19
(233.4 mg, 79%) as a white solid: Rf 0.51 (3:1 petroleum ether–
EtOAc);ESIMS:calcdfor[M+Na]+ m/z467.2; found:467.3; HRESIMS:
m/z calcd for C24H28O8Na+ 467.1682; found 467.1687.
To a solution of the mixture 18 and 19 (233.4 mg, 0.53 mmol) in
dry CH2Cl2 (30 mL), AzmbOH (139.5 mg, 0.79 mmol), EDCꢁHCl
(201.3 mg, 1.1 mmol), and DMAP (128.1 mg, 1.1 mmol) were
added under argon. The mixture was stirred for 12 h, diluted with
CH2Cl2 (100 mL), washed with water (50 mL), 1 M HCl (2 ꢃ 50 mL),
saturated aqueous NaHCO3 (2 ꢃ 50 mL), and brine (2 ꢃ 50 mL),
dried over Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (6:1 petroleum ether–EtOAc)
to give a mixture of 20 and 21 (305.4 mg, 96%) as a white solid:
Rf 0.40 (4:1, petroleum ether–EtOAc); ESIMS: calcd for [M+Na]+
m/z 626.2; found: 626.3; HRESIMS: m/z calcd for C32H33N3O9Na+
626.2114; found 626.2094.
To a solution of the crude product in dry DMF (20 mL) was
added NaH (985.6 mg, 24.6 mmol) at 0 °C. The mixture was stirred
under these conditions for 30 min and then BnBr (4.2 mL,
35.2 mmol) was added dropwise. The mixture was allowed to stir
for 2 h at room temperature. When TLC (3:1 petroleum ether–
EtOAc) showed complete conversion, MeOH (2 mL) was carefully
added to destroy excess NaH, and the mixture was diluted with
CH2Cl2 (50 mL). The organic layer was shaken with 1 M HCl
(3 ꢃ 50 mL) followed by washing with saturated aq NaHCO3 solu-
tion (3 ꢃ 50 mL) and water (3 ꢃ 50 mL). Finally, the organic layer
was separated, dried over Na2SO4, and evaporated to give a syrup.
The residue was dissolved in dry CH2Cl2 (50 mL) at 0 °C. To this
cold suspension was added Ac2O (1.7 mL, 17.6 mmol), and then tri-
ethylamine (1.7 mL, 12.3 mmol) was added dropwise over a period
of 30 min, and the mixture was stirred for 30 min. Then, DMAP
(59.8 mg, 0.5 mmol) was added in one portion. The reaction mix-
ture was stirred for 4 h while warming to room temperature. The
reaction was quenched with MeOH (5 mL) and concentrated. The
residue was diluted with CH2Cl2 (50 mL), washed with 1 M HCl
(2 ꢃ 50 mL), saturated aq NaHCO3 (2 ꢃ 50 mL), and brine (50 mL),
dried over Na2SO4, filtered, and concentrated under diminished
pressure.
The crude product was dissolved in CH2Cl2 (50 mL) and p-TolSH
(1.7 g, 13.6 mmol) was added at 0 °C. To the cold solution, BF3ꢁEt2O
(1.7 mL, 13.6 mmol) was added dropwise over a period of 30 min.
The reaction mixture was allowed to stir for another 2 h while
warming to room temperature. After the reaction was complete
as judged by TLC, it was quenched by the addition of aq NaHCO3
(25 mL). The mixture was extracted with CH2Cl2 (100 mL). The or-
ganic layer was washed with saturated aq NaHCO3 (2 ꢃ 50 mL),
water (2 ꢃ 50 mL), brine (2 ꢃ 50 mL), dried over Na2SO4, filtered,
and concentrated under diminished pressure. Purification of the
crude reaction product by column chromatography on silica gel
(10:1?2:1 petroleum ether–EtOAc) furnished pure p-tolyl 3,4-di-
The mixture of 20 and 21 (305.4 mg, 0.50 mmol) was dissolved
in 80% AcOH (30 mL) and stirred for 2 h at 80 °C, then the reaction
mixture was concentrated. The residue was purified by silica gel
column chromatography (2:3 petroleum ether–EtOAc) to give
compound 8 as a colorless oil (123.6 mg, 47%): Rf 0.46 (2:3 petro-
leum ether–EtOAc); ½a D22
ꢂ
+14.7 (c 0.2, CHCl3); 1H NMR (600 MHz,
DMSO-d6): d 7.81 (d, 1H, J 7.1 Hz, Ph), 7.65 (t, 1H, J 7.7 Hz, Ph),
7.56 (d, 1H, J 7.1 Hz, Ph), 7.50 (t, 1H, J 7.7 Hz, Ph), 6.92 (d, 2H, J
8.8 Hz, Ph), 6.82 (d, 2H, J 8.8 Hz, Ph), 5.61 (d, 1H, J 5.5 Hz, 4-OH),
5.40 (d, 1H, J 8.3 Hz, H-1), 5.31 (t, 1H, J 9.3 Hz, H-3), 5.14 (dd, 1H,
J 9.9, 8.2 Hz, H-2), 4.79 (t, 1H, J 6.1 Hz, 6-OH), 4.74 (s, 2H, PhCH2),
3.75 (dd, 1H, J 11.0, 5.5 Hz, H-4), 3.67 (s, 3H, OMe), 3.65–3.55 (m,
3H, H-6 and H-5), 2.28–2.18 (m, 2H, COCH2), 1.44–1.40 (m, 2H,
CH2CH3), 0.72 (t, 3H, J 7.1 Hz, CH3); 13C NMR (150 MHz, DMSO-
d6): d 172.2, 164.9, 154.7, 150.6, 136.4, 133.1, 130.6, 130.3, 128.5,
128.4, 117.5, 114.5, 98.4, 76.7, 74.6, 72.2, 67.5, 60.1, 55.3, 51.7,
35.4, 17.8, 13.1; ESIMS: calcd for [M+Na]+ m/z 538.2; found: 538.2.
3.12. 4-Methoxyphenyl 3-O-[2-(azidomethyl)benzoyl]-2-O-
butyryl-b-D-glucopyranoside (22)
O-benzyl-2-O-acetyl-1-thio-b-
oil (2.4 g, 74% for six steps): Rf 0.51 (4:1 petroleum ether–EtOAc);
+17.2 (c 0.2, CHCl3); 1H NMR (600 MHz, CDCl3): d 7.41–7.26
(m, 12H, Ph), 7.06 (d, 2H, J 7.8 Hz, Ph), 5.39 (t, 1H, J 9.6 Hz, H-2),
4.98 (d, 1H, J 11.5 Hz, PhCHH), 4.68 (d, 1H, J 12.4 Hz, PhCHH),
4.64 (d, 1H, J 11.5 Hz, PhCHH), 4.56 (d, 1H, J 12.0 Hz, PhCHH),
4.53 (d, 1H, J 9.6 Hz, H-1), 3.65 (d, 1H, J 2.7 Hz, H-4), 3.56 (dd,
D-fucopyranoside (25) as a colorless
Compound 22 as a filiation of compound 8 was obtained as a
white solid (99.8 mg, 38%): Rf 0.51 (2:3 petroleum ether–EtOAc);
½ ꢂ
a 2D2
½
a 2D2
ꢂ
+51.8 (c 0.05, CHCl3); 1H NMR (600 MHz, DMSO-d6): d 7.92
(d, 1H, J 7.7 Hz, Ph), 7.67 (t, 1H, J 7.7 Hz, Ph), 7.57 (d, 1H, J 7.7 Hz,
Ph), 7.53 (t, 1H, J 7.7 Hz, Ph), 6.96 (d, 2H, J 9.4 Hz, Ph), 6.87 (d,
2H, J 9.3 Hz, Ph), 5.70 (d, 1H, J 6.1 Hz, 4-OH), 5.39 (t, 1H, J 9.3 Hz,

Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
757
1H, J 9.6, 2.7 Hz, H-3), 3.53 (q, 1H, J 6.6 Hz, H-5), 2.31 (s, 3H,
PhCH3), 2.06 (s, 3H, COCH3), 1.26 (d, 3H, J 6.6 Hz, 6-Me). 13C NMR
(150 MHz, CDCl3): d 169.5, 138.4, 137.9, 137.5, 132.4, 129.9,
129.4, 128.4–127.4, 86.8, 81.9, 75.5, 74.8, 74.3, 72.0, 69.7, 21.1,
17.2. ESIMS: calcd for [M+Na]+ m/z 515.2; found: 515.2.
80.9, 75.4, 74.5, 74.2, 72.6, 72.2, 72.0, 71.5, 70.7, 68.8, 67.3, 55.6,
52.8, 37.8, 35.9, 29.6, 28.0, 18.2, 16.7, 13.6, 13.4. ESIMS: calcd for
[M+Na]+ m/z 962.4; found: 962.5.
3.16. 4-Methoxyphenyl 3,4-di-O-benzyl-2-O-levulinoyl-b-
fucopyranosyl-(1?6)-2-O-[2-(azidomethyl)benzoyl]-3,4-di-O-
butyl-b- -glucopyranoside (27)
D-
3.14. p-Tolyl 3,4-di-O-benzyl-2-O-levulinyl-1-thio-b-
D-
D
fucopyranoside (9)
Compound 26 (54.7 mg, 0.06 mmol) was dissolved in pyridine
(5 mL) and butyryl chloride (12.4 L, 0.12 mmol) was added drop-
To a solution of 25 (0.96 g, 3.6 mmol) in dry MeOH (25 mL) and
CH2Cl2 (25 mL) was added NaOMe until pH 8.5–9.0. The reaction
mixture was stirred at room temperature for 30 h, after which
the reaction mixture was neutralized with Dowex 50 ꢃ 8(H+) resin
until pH 7.0, filtered, and concentrated. To a solution of the residue
in dry CH2Cl2 (50 mL), levulinic acid (0.5 g, 2.9 mmol), EDCꢁHCl
(0.3 g, 2.9 mmol) and DMAP (61.0 mg, 0.5 mmol) were added un-
der argon. The mixture was stirred for 12 h, diluted with CH2Cl2
(50 mL), washed with water (50 mL), 1 M HCl (2 ꢃ 50 mL), satu-
rated aq NaHCO3 (2 ꢃ 50 mL), and brine (2 ꢃ 50 mL), dried over
Na2SO4, and concentrated. The residue was purified by silica gel
column chromatography (10:1 petroleum ether–EtOAc) to give 9
(0.9 g, 99% for two steps) as a white solid: Rf 0.42 (3:1 petroleum
l
wise at 0 °C. The solution was stirred for 2 h while warming to
room temperature. After the reaction was complete as judged by
TLC, the mixture was diluted with CHCl3 (20 mL) and washed con-
secutively with water (20 mL), HCl (3 ꢃ 20 mL), saturated aq NaH-
CO3 (2 ꢃ 10 mL), and brine (20 mL). The organic layer was dried
(Na2SO4) and filtered. Purification of the residue on a silica gel col-
umn (10:1?3:1 petroleum ether–EtOAc) gave 27 (52.0 mg, 88%) as
a syrup: Rf 0.52 (2:1 petroleum ether–EtOAc); ½a D22
ꢀ7.7 (c 0.3,
ꢂ
CHCl3); 1H NMR (600 MHz, CDCl3): d 7.89 (d, 1H, J 7.1 Hz, Ph),
7.55 (t, 1H, J 7.7 Hz, Ph), 7.49 (d, 1H, J 7.7 Hz, Ph), 7.38–7.26 (m,
11H, Ph), 6.93 (d, 2H, J 8.8 Hz, Ph), 6.82 (d, 2H, J 8.8 Hz, Ph), 5.48
(t, 1H, J 9.9 Hz, H-3), 5.44 (t, 1H, J 9.4 Hz, H-2), 5.37 (dd, 1H, J
9.4, 8.2 Hz, H-20), 5.14 (d, 1H, J 7.7 Hz, H-1), 5.02 (t, 1H, J 9.9 Hz,
H-4), 4.97 (d, 1H, J 11.6 Hz, PhCH2), 4.79 (d, 1H, J 14.9 Hz, PhCH2),
4.75 (d, 1H, J 14.3 Hz, PhCH2), 4.66 (d, 2H, J 13.2 Hz, PhCH2), 4.60
(d, 1H, J 12.1 Hz, PhCH2), 4.42 (d, 1H, J 8.3 Hz, H-10), 3.99 (t, 1H, J
8.8 Hz, H-5), 3.85 (d, 1H, J 9.9 Hz, H-6a), 3.74 (s, 3H, OMe), 3.66
(dd, 1H, J 11.0, 8.3 Hz, H-6b), 3.57 (br s, 1H, H-40), 3.48 (dd, 1H, J
9.9, 2.7 Hz, H-30), 3.43 (q, 1H, J 6.1 Hz, H-50), 3.63–3.59 (m, 3H,
H-30, H-50, and H-5), 2.52–2.17 (m, 8H, 4 ꢃ COCH2), 2.06 (s, 3H,
COCH3), 1.61–1.57 (m, 2H, CH2CH3), 1.50–1.47 (m, 2H, CH2CH3),
1.17 (d, 3H, J 6.1 Hz, 6-Me), 0.91 (t, 3H, J 7.7 Hz, CH3), 0.78 (t 3H,
J 7.7 Hz, CH3); 13C NMR (150 MHz, CDCl3): d 207.0, 173.7, 171.7,
165.2, 155.6, 151.2, 138.2, 137.5, 132.9, 131.1, 129.6, 128.5–
127.6, 118.5, 114.7, 100.9, 100.4, 80.6, 75.5, 75.2, 74.8, 74.6, 72.5,
72.0, 71.3, 71.1, 69.8, 67.4, 55.6, 52.9, 37.9, 36.1, 30.8, 29.8, 29.7,
28.0, 18.3, 16.8, 14.1, 13.4; ESIMS: calcd for [M+Na]+ m/z 1032.4;
found: 1032.7.
ether–EtOAc); ½a D22
ꢂ
+23.2 (c 0.1, CHCl3); 1H NMR (600 MHz, CDCl3):
d 7.40–7.25 (m, 12H, Ph), 7.05 (d, 2H, J 8.2 Hz, Ph), 5.37 (t, 1H, J
9.9 Hz, H-2), 4.97 (d, 1H, J 11.5 Hz, PhCHH), 4.67 (d, 1H, J 12.1 Hz,
PhCHH), 4.62 (d, 1H, J 11.6 Hz, PhCHH), 4.59 (d, 1H, J 12.7 Hz,
PhCHH), 4.52 (d, 1H, J 9.9 Hz, H-1), 3.62 (d, 1H, J 2.2 Hz, H-4),
3.55 (dd, 1H, J 9.4, 2.8 Hz, H-3), 3.51 (q, 1H, J 6.6 Hz, H-5), 2.81–
2.56 (m, 4H, COCH2CH2CO), 2.30 (s, 3H, PhCH3), 2.17 (s, 3H, COCH3),
1.24 (d, 3H, J 6.6 Hz, 6-CH3); 13C NMR (150 MHz, CDCl3): d 206.4,
171.4, 138.4, 138.0, 137.5, 129.4, 128.4, 128.1, 127.7, 127.6,
127.4, 86.9, 81.8, 75.6, 74.8, 74.3, 72.2, 70.1, 37.9, 29.9, 28.1,
21.1, 17.2; ESIMS: calcd for [M+Na]+ m/z 571.2; found: 571.2.
3.15. 4-Methoxyphenyl 3,4-di-O-benzyl-2-O-levulinoyl-b-
fucopyranosyl-(1?6)-2-O-[2-(azidomethyl)benzoyl]-3-O-
D-
butyryl-b-
D-glucopyranoside (26)
To mixture of
a
8
(281.5 mg, 0.55 mmol), 9 (359.5 mg,
0.66 mmol), and 4 Å molecular sieves in dry CH2Cl2 (15 mL) and
MeCN (15 mL), NIS (198.9 mg, 0.88 mmol) and AgOTf (28.3 mg,
0.11 mmol) were added at 0 °C under argon. The mixture was stir-
red for an additional 12 h while warming to room temperature.
After the reaction was complete as judged by TLC, the mixture
was filtered and concentrated. Then the resulting residue was di-
luted with CH2Cl2 (50 mL) and washed with 10% aq Na2S2O3
(25 mL) and brine (2 ꢃ 25 mL). The organic layer was dried over
Na2SO4, filtered, and concentrated. The resulting residue was puri-
fied by silica gel column chromatography (3:1 petroleum ether–
EtOAc) to give 26 (440.8 mg, 86%) as a syrup: Rf 0.34 (1:1 petro-
3.17. 4-Methoxyphenyl 3,4-di-O-benzyl-b-D-fucopyranosyl-
(1?6)-2-O-[2-(azidomethyl)benzoyl]-3,4- di-O-butyryl-b-D-
glucopyranoside (28)
To a stirred solution of 27 (340.1 mg, 0.34 mmol) in CH2Cl2
(10 mL) and MeOH (10 mL) was added NH2NH2ꢁAcOH (309.8 mg,
3.4 mmol). After 2 h, the solution was concentrated and the residue
was purified by silica gel column chromatography (3:1 petroleum
ether–EtOAc) to afford 28 (260.8 mg, 85%) as a syrup: Rf 0.42 (3:1
petroleum ether–EtOAc);
½
a 2D2 +5.4 (c 0.5, CHCl3); 1H NMR
ꢂ
(600 MHz, DMSO-d6): d 7.82 (d, 1H, J 7.1 Hz, Ph), 7.66 (t, 1H, J
7.7 Hz, Ph), 7.56 (d, 1H, J 7.7 Hz, Ph), 7.50 (t, 1H, J 7.7 Hz, Ph),
7.43–7.26 (m, 10H, Ph), 6.97 (d, 2H, J 8.8 Hz, Ph), 6.82 (d, 2H, J
9.4 Hz, Ph), 5.64 (t, 1H, J 9.8 Hz, H-3), 5.48 (d, 1H, J 8.2 Hz, H-1),
5.30 (dd, 1H, J 9.3, 8.3 Hz, H-2), 5.09 (d, 1H, J 4.9 Hz, 20-OH), 5.04
(t, 1H, J 9.9 Hz, H-4), 4.83 (d, 1H, J 11.0 Hz, PhCH2), 4.77–4.71 (m,
4H, PhCH2), 4.59 (d, 1H, J 11.5 Hz, PhCH2), 4.22 (d, 1H, J 7.7 Hz,
H-10), 4.20–4.18 (m, 1H, H-5), 3.75–3.73 (m, 2H, H-6a and H-40),
3.62 (s, 3H, OMe), 3.62–3.53 (m, 3H, H-6b, H-20 and H-50), 3.39
(dd, 1H, J 9.9, 2.8 Hz, H-30), 2.32–2.14 (m, 4H, 2 ꢃ COCH2), 1.53–
1.47 (m, 2H, CH2CH3), 1.42–1.36 (m, 2H, CH2CH3), 1.15 (d, 3H, J
6.5 Hz, 6-Me), 0.85 (t, 3H, J 7.7 Hz, CH3), 0.70 (t, 3H, J 7.7 Hz,
CH3); 13C NMR (150 MHz, CDCl3): d 172.7, 172.4, 165.0, 155.7,
150.9, 138.4, 137.6, 133.0, 131.0, 129.7, 128.4–127.6, 118.5,
114.7, 103.6, 100.0, 82.2, 76.2, 74.7, 74.0, 72.9, 72.3, 72.0, 71.5,
70.9, 68.8, 68.1, 55.6, 52.8, 35.9, 35.8, 30.8, 18.2, 16.8, 13.6, 13.4;
ESIMS: calcd for [M+Na]+ m/z 934.4; found: 934.5.
leum ether–EtOAc); ½a D22
ꢂ
ꢀ5.7 (c 0.25, CHCl3); 1H NMR (600 MHz,
DMSO-d6): d 7.81 (d, 1H, J 7.7 Hz, Ph), 7.65 (t, 1H, J 7.7 Hz, Ph),
7.55 (d, 1H, J 7.7 Hz, Ph), 7.50 (t, 1H, J 7.7 Hz, Ph), 7.37–7.30 (m,
10H, Ph), 6.91 (d, 2H, J 9.3 Hz, Ph), 6.81 (d, 2H, J 9.3 Hz, Ph), 5.65
(d, 1H, J 6.1 Hz, 4-OH), 5.38 (d, 1H, J 8.3 Hz, H-1), 5.32 (t, 1H, J
9.4 Hz, H-3), 5.12 (dd, 1H, J 9.9, 8.3 Hz, H-2), 4.99 (dd, 1H, J 9.9,
8.2 Hz, H-20), 4.83 (d, 1H, J 11.6 Hz, PhCH2), 4.74 (s, 2H, PhCH2),
4.71 (d, 1H, J 12.1 Hz, PhCH2), 4.59 (d, 1H, J 11.5 Hz, PhCH2), 4.56
(d, 1H, J 12.1 Hz, PhCH2), 4.46 (d, 1H, J 7.7 Hz, H-10), 3.98 (d, 1H, J
11.0 Hz, H-6a), 3.86 (d, 1H, J 2.2 Hz, H-6b), 3.82 (t, 1H, J 8.8 Hz,
H-40), 3.64 (s, 3H, OMe), 3.63–3.59 (m, 3H, H-30, H-50, and H-5),
3.51–3.47 (m, 1H, H-4), 2.62–2.18 (m, 6H, 3 ꢃ COCH2), 2.07 (s,
3H, COCH3), 1.45–1.38 (m, 2H, CH2CH3), 1.17 (d, 3H, J = 6.6 Hz, 6-
Me), 0.71 (t, 3H, J = 7.7 Hz, CH3); 13C NMR (150 MHz, CDCl3): d
206.4, 172.6, 172.3, 171.5, 165.0, 155.5, 151.2, 138.3, 138.0,
137.5, 133.0, 131.0, 129.7, 128.5–127.5, 118.0, 114.9, 100.9, 99.9,

758
Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
3.18. 4-Methoxyphenyl 3,4-di-O-benzyl-6-deoxy-b-
talopyranosyl-(1?6)-2-O-[(2-azidomethyl)benzoyl]-3,4-di-O-
butyryl-b- -glucopyranoside (29)
D
-
and H-10), 4.07–4.05 (m, 1H, H-40), 3.96 (dd, 1H, J 11.9, 1.3 Hz, H-
6a), 3.86–3.85 (m, 1H, H-30), 3.69 (dd, 1H, J 11.9, 6.9 Hz, H-6b),
3.59 (br s, 1H, OH), 3.43–3.40 (m, 2H, H-50 and H-20), 2.27–2.25
(m, 2H, COCH2), 2.18 (t, 2H, J 7.5 Hz, COCH2), 1.61–1.56 (m, 2H,
COCH2CH2), 1.52–1.46 (m, 2H, COCH2CH2), 1.25 (d, 1H, J 6.9 Hz,
6-Me), 0.90 (t, 3H, J 7.3 Hz, CH3), 0.77 (t, 3H, J 7.3 Hz, CH3); 13CNMR
(150 MHz, CDCl3): d 172.5, 172.4, 171.2, 160.8, 138.2, 137.9, 137.5,
133.5, 131.6, 129.5, 128.7–127.6, 126.7, 101.5, 92.8, 75.6, 72.6,
71.1, 70.6, 69.5, 69.2, 68.2, 68.0, 67.5, 60.4, 52.9, 35.8, 29.7, 21.0,
18.3, 18.2, 16.6, 14.2, 13.6, 13.4; ESIMS: calcd for [M-CCl3CN+Na]+
m/z 828.3; found: 828.5.
D
A solution of 28 (324.9 mg, 0.36 mmol) in CH2Cl2 (5 mL) was
added to stirred solution of Dess–Martin periodinane
a
(755.7 mg, 1.8 mmol) in CH2Cl2 (20 mL) at room temperature. Then
the solution was stirred for 4 h. After the reaction was complete as
judged by TLC, the mixture was diluted with CH2Cl2 (50 mL) and
washed with 10% aq Na2S2O3 (30 mL), saturated aq NaHCO3
(30 mL), and brine (30 mL). The organic layer was dried over
Na2SO4, filtered, and concentrated under diminished pressure.
The crude compound was dissolved in CH2Cl2 (10 mL) and
MeOH (10 mL). Then NaBH4 (136.0 mg, 3.6 mmol) was added at
0 °C. After 0.5 h, the reaction was complete as judged by TLC. The
mixture was diluted with CH2Cl2 (50 mL), and washed with water
(30 mL), 1 M HCl (30 mL), saturated aq NaHCO3 (30 mL), and brine
(30 mL). The organic layer was dried over Na2SO4, filtered, concen-
trated, and the residue was purified by silica gel column chroma-
tography (4:1 petroleum ether–EtOAc) to afford 29 (309.3 mg,
3.20. p-Tolyl 2,3,4-tri-O-benzoyl-6-deoxy-1-thio-b-L-
glucopyranoside (34)
6-Deoxy-b-L
-glucoside perbenzoate18 33 (4.6 g, 7.9 mmol) was
dissolved in CH2Cl2 (100 mL) and p-TolSH (2.0 g, 15.8 mmol) was
added at 0 °C. To the cold solution, BF3ꢁEt2O (2.0 mL, 15.9 mmol)
was added dropwise over a period of 30 min and the reaction mix-
ture was allowed to stir for another 2 h while warming to room
temperature. The reaction was quenched by the addition of satu-
rated aq NaHCO3 (100 mL) and the mixture was extracted with
CH2Cl2 (150 mL). The organic layer was washed with water
(100 mL), saturated aq NaHCO3 (100 mL), and brine (100 mL), dried
over Na2SO4, and concentrated under diminished pressure. Purifi-
cation of the crude reaction product by column chromatography
on silica gel (50:1 ether–EtOAc) furnished pure 34, which could
be crystallized from petroleum ether–EtOAc; (2.9 g, 63%): Rf
96%) as a syrup: Rf 0.38 (2:1 petroleum ether–EtOAc); ½a D18
ꢀ10.8
ꢂ
(c 0.35, CHCl3); 1H NMR (600 MHz, DMSO-d6): d 7.82 (d, 1H, J
7.8 Hz, Ph), 7.66 (m, 1H, Ph), 7.56 (d, 1H, J 6.8 Hz, Ph), 7.50 (t,
1H, J 7.8 Hz, Ph), 7.43–7.26 (m, 10H, Ph), 6.94 (dd, 2H, J 6.9,
2.3 Hz, Ph), 6.83 (dd, 2H, J 6.9, 2.3 Hz, Ph), 5.65 (t, 1H, J 9.6 Hz, H-
3), 5.56 (d, 1H, J 7.7 Hz, H-1), 5.29 (dd, 1H, J 10.1, 8.3 Hz, H-2),
5.04 (t, 1H, J 10.1 Hz, H-4), 4.89 (d, 1H, J 11.5 Hz, PhCH2), 4.77–
4.71 (m, 2H, PhCH2), 4.64 (d, 1H, J 11.9 Hz, PhCH2), 4.59 (d, 1H, J
11.0 Hz, PhCH2), 4.54 (d, 1H, J 11.9 Hz, PhCH2), 4.26 (s, 1H, H-10),
4.19–4.16 (m, 1H, H-5), 3.87 (br d, 1H, J 8.7 Hz H-20), 3.82 (dd,
1H, J 11.5, 1.9 Hz, H-6a), 3.77 (br s, 1H, H-40), 3.63 (s, 3H, OMe),
3.58–3.55 (m, 2H, H-6b and OH), 3.52–3.49 (m, 1H, H-5), 3.48 (t,
1H, J 2.8 Hz, H-30), 2.34–2.15 (m, 4H, 2 ꢃ COCH2), 1.52–1.47 (m,
2H, CH2CH3), 1.41–1.36 (m, 2H, CH2CH3), 1.13 (d, 3H, J 6.0 Hz, 6-
Me), 0.84 (t, 3H, J 7.3 Hz, CH3), 0.70 (t, 3H, J 7.3 Hz, CH3); 13C
NMR (150 MHz, CDCl3): 206.6, 172.6, 172.3, 165.0, 155.5, 150.9,
137.8, 137.5, 133.0, 131.1, 129.7, 128.5–127.6, 117.7, 114.7,
102.3, 99.4, 77.7, 75.7, 74.4, 72.3, 71.9, 71.1, 69.8, 69.0, 68.9,
68.4, 55.6, 52.8, 35.9, 30.8, 29.6, 18.2, 16.7, 13.6, 13.4; [M+Na]+
m/z 934.4; found: 934.5.
+0.57 (3:1 petroleum ether–EtOAc); mp 149–150 °C; ½a D18
ꢀ6.0 (c
ꢂ
0.2, CHCl3); 1H NMR (600 MHz, CDCl3): d 7.97 (dd, 2H, J 9.6,
0.9 Hz, Ph), 7.92 (dd, 2H, J 8.2, 0.9 Hz, Ph), 7.78 (dd, 2H, J 8.3,
0.9 Hz, Ph), 7.54–7.49 (m, 2H, Ph), 7.42–7.35 (m, 7H, Ph), 7.23 (t,
2H, J 8.2 Hz, Ph), 7.13 (d, 1H, J 7.7 Hz, Ph), 5.81 (t, 1H, J 9.6 Hz, H-
3), 5.42 (t, 1H, J 9.6 Hz, H-2), 5.29 (t, 1H, J 9.6 Hz, H-4), 4.93 (d,
1H, J 10.1 Hz, H-1), 3.88 (qd, 1 H, J 9.6, 5.9 Hz, H-5), 1.39 (d, 3H, J
6.4 Hz, 6-Me); 13C NMR (150 MHz, DMSO-d6): d 165.8, 165.4,
165.0, 138.6, 133.8, 133.3, 133.2, 129.8–128.2, 86.1, 74.9, 74.2,
73.6, 70.9, 21.2, 17.8; HRESIMS: calcd for C34H30O7SNa+ [M+Na]+
m/z 605.1610; found: 605.1602.
3.21. p-Tolyl 2,3,4-tri-O-benzyl-6-deoxy-1-thio-b-L-
3.19. 3,4-Di-O-benzyl-6-deoxy-b-
D-talopyranosyl-(1?6)-2-O-
glucopyranoside (4)
[(2-azidomethyl)benzoyl]-3,4-di-O-butyryl-b-D-glucopyranosyl
trichloroacetimidate (3)
Compound 34 (1.00 g, 1.7 mmol) was dissolved in MeOH
(25 mL) and NaOMe was added to the solution until pH 8.5. The
mixture was stirred at room temperature for about 1 h, and then
it was neutralized with Dowex 50 ꢃ 8(H+) resin until pH 7.0, fil-
tered, and concentrated. The dried residue was dissolved in DMF
(20 mL) and cooled to 0 °C. Sodium hydride (60%, 247.3 mg,
6.0 mmol) was added, followed by benzyl bromide (1.8 mL,
10.2 mmol). As shown by TLC, the reaction was complete after
4 h at 0 °C. The mixture was diluted with water (100 mL) and ex-
tracted with CH2Cl2 (3 ꢃ 100 mL). The combined organic extracts
were combined, dried over MgSO4, and concentrated. Silica gel col-
umn chromatography of the crude product (100:1 petroleum
ether–EtOAc) furnished 4 (549.0 mg, 59%) as a colorless oil: Rf
To a solution of 29 (309.3 mg, 0.34 mmol) in MeCN (15 mL) and
water (3 mL) was added ammonium cerium(IV) nitrate (930.3 mg,
1.69 mmol) and the mixture was stirred for 2 h at room tempera-
ture. The reaction mixture was diluted with EtOAc (40 mL), succes-
sively washed with saturated aq NaHCO3 (20 mL) and brine
(20 mL), dried over Na2SO4, and concentrated. The resulting resi-
due was purified by flash column chromatography (1:1 petroleum
ether–EtOAc) to give a syrup (263.0 mg, 96%) which was used di-
rectly for the preparation of donor 3. To a stirred solution of it
(263.0 mg, 0.32 mmol) and CCl3CN (197.4
(20 mL) at 0 °C was added DBU (24.7 L, 0.16 mmol). After 1 h, the
solution was concentrated. The residue was purified by silica gel
column chromatography (10:1 petroleum ether–EtOAc) to afford
3 (280.8 mg, 91%) as a syrup: Rf 0.44 (2:1 petroleum ether–EtOAc);
lL, 2.0 mmol) in CH2Cl2
l
0.53 (10:1, petroleum ether–EtOAc); ½a D22
ꢂ
ꢀ13.8 (c 0.2, CHCl3); 1H
NMR (600 MHz, CDCl3): d 7.45 (d, 2H, J 7.8 Hz, Ph), 7.40 (dd, 2H, J
8.2, 1.4 Hz, Ph), 7.35–7.28 (m, 13H, Ph), 7.11 (d, 1H, J 7.8 Hz, Ph),
4.91 (d, 1H, J 9.6 Hz, PhCHH), 4.90 (d, 1H, J 10.1 Hz, PhCHH), 4.86
(d, 1H, J 10.5 Hz, PhCHH), 4.84 (d, 1H, J 10.5 Hz, PhCHH), 4.90 (d,
1H, J = 10.1 Hz, PhCHH), 4.74 (d, 1H, J 10.1 Hz, PhCHH), 4.65 (d,
1H, J 10.9 Hz, PhCHH), 4.59 (d, 1H, J 9.6 Hz, H-1), 3.66 (t, 1H, J
9.1 Hz, H-3), 3.46 (t, 1H, J 9.6 Hz, H-2), 3.39 (qd, 1 H, J 9.6, 6.0 Hz,
H-5), 3.20 (t, 1H, J 9.2 Hz, H-4), 2.34 (s, 3H, PhCH3), 1.34 (d, 3 H, J
6.4 Hz, 6-Me); 13C NMR (150 MHz, DMSO-d6): d 138.4, 138.1,
½
a 2D0 +19.1 (c 0.22, CHCl3); 1HNMR (600 MHz, CDCl3): d 8.49 (s, 1H,
ꢂ
NH), 7.95 (dd, 1H, J 7.7, 1.3 Hz, Ph), 7.57–7.31 (m, 13H, Ph), 6.61 (d,
1H, J 3.7 Hz, H-1), 5.79 (t, 1H, J 9.9 Hz, H-3), 5.29 (dd, 1H, J 10.1,
3.7 Hz, H-2), 5.14 (t, 1H, J 10.1 Hz, H-4), 5.01 (d, 1H, J 11.0 Hz,
PhCHH), 4.84 (d, 1H, J 11.9 Hz, PhCHH), 4.83 (d, 1H, J 14.6 Hz,
PhCHH), 4.77 (d, 1H, J 14.6 Hz, PhCHH), 4.63 (d, 1H, J 11.0 Hz,
PhCHH), 4.56 (d, 1H, J 11.9 Hz, PhCHH), 4.35–4.32 (m, 2H, H-5

Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
759
138.0, 137.7, 132.6, 129.6, 128.4–127.7, 87.8, 86.6, 83.3, 81.2, 75.5,
71.7, 70.5, 69.1, 69.0, 52.7, 43.7, 35.8, 35.0, 34.2, 31.9, 30.9, 30.0–
29.2, 25.3, 24.9, 23.8, 22.7, 18.3, 18.1, 16.8, 14.1, 13.6, 13.4. ESI-
MS: calcd for [M+Na]+ m/z 1631.9; found:1632.0.
18.1. ESI-MS: calcd for [M+Na]+ m/z 563.2; found: 563.2.
3.22. (10R)-2-Nonadecanone-10-yl 3,4-di-O-benzyl-6-deoxy-b-
D
-talopyranosyl-(1?6)- 2-O-[(2-azidomethyl)-benzoyl]-3,4-di-O-
butyryl-b- -glucopyranosyl(1?2)-3,4,6-tri-O-benzyl-b-
glucopyranoside (30)
3.24. (10R)-2-Nonadecanone-10-yl 2,3,4-tri-O-benzyl-6-deoxy-
D
D-
b-D
-talopyranosyl-(1?6)-3,4-di-O-butyryl-b-
D-glucopyranosyl-
(1?2)-3,4,6-tri-O-benzyl-b-
D
-glucopyranoside (32)
To
0.30 mmol), and 4 Å molecular sieves in dry CH2Cl2 (15 mL),
TMSOTf (8 L, 0.04 mmol) was added at 0 °C under argon. The
a
solution of
2
(162.0 mg, 0.22 mmol),
3
(285.4 mg,
To a solution of 31 (10 mg, 0.006 mmol) in THF (5 mL), Bu3P
(10 mg) and water (0.1 mL) were added at 50 °C under argon.
The reaction mixture was stirred under these conditions for 1 h,
until TLC indicated that the reaction was complete. The reaction
mixture was diluted with EtOAc, washed with saturated aq NaH-
CO3 (5 mL) and brine (5 mL), dried over Na2SO4, and concentrated
under diminished pressure. The residue was purified by silica gel
column chromatography (6:1 petroleum ether–EtOAc) to give 32
(7.6 mg, 85%) as a syrup: Rf 0.50 (3:1 petroleum ether–EtOAc);
l
reaction mixture was stirred for 1 h until TLC indicated that the
reaction was complete. The reaction was quenched by the addition
of Et3N (two drops) and concentrated. The residue was purified by
silica gel column chromatography (4:1 petroleum ether–EtOAc) to
give 30 (254.1 mg, 76%) as a syrup: Rf 0.39 (4:1 petroleum ether–
EtOAc); ½a 2D2
ꢂ
ꢀ16.0 (c 0.2, CHCl3); 1HNMR (600 MHz, CDCl3): d
7.72 (d, 1H, J 6.8 Hz, Ph), 7.49–7.15 (m, 31H, Ph), 7.72 (dd, 1H, J
7.8, 1.9 Hz, Ph), 5.32 (t, 1H J 9.6 Hz, H-30), 5.21–5.16 (m, 2H, H-10
and H-20), 4.97 (d, 1H, J 11.0 Hz, PhCH2), 4.91 (t, 1H J 9.6 Hz, H-
40), 4.87 (d, 1H, J 14.2 Hz, PhCH2), 4.84 (d, 1H, J 11.4 Hz, PhCH2),
4.62–4.55 (m, 7H, PhCH2), 4.43 (d, 1H, J 11.0 Hz, PhCH2), 4.37 (d,
1H, J 11.0 Hz, PhCH2), 4.30 (d, 1H, J = 7.3 Hz, H-1), 4.27 (d, 1H,
J = 11.9 Hz, H-6a0), 4.22 (s, 1H, H-100), 4.21 (d, 1H, J 12.4 Hz, H-
6b0), 3.90 (d, 1H, J 11.0 Hz, H-6a), 3.79–3.72 (m, 2H, H-50 and H-
6b), 3.66–3.34 (m, 9H, H-2, H-3, H-4, H-5, H-200, H-300, H-400, H-500
and OCH), 2.37 (t, 2H, J 7.40 Hz, COCH2), 2.24–2.21 (m, 2H, COCH2),
2.14–2.11 (m, 2H, COCH2), 2.10 (s, 3H, COCH3), 1.62–1.23 (m, 35H,
2 ꢃ CH2CH2CO, 14 ꢃ CH2 and 600- Me); 0.91–0.86 (m, 6H, 2 ꢃ CH3),
0.73 (t, 3H, J = 7.6 Hz, CH3). 13C NMR (150 MHz, CDCl3): 209.1,
172.6, 172.3, 164.7, 138.6, 138.0, 137.7, 137.6, 137.4, 132.7,
130.8, 129.8, 128.4–126.9, 102.1, 101.8, 99.6, 85.8, 82.2, 78.6,
78.1, 77.9, 77.6, 75.5, 75.0, 74.7, 74.6, 74.3, 73.0, 72.3, 70.8, 70.0,
69.2, 69.1, 68.5, 68.4, 52.7, 43.7, 35.8, 31.9, 30.9, 30.0–29.2, 25.5,
24.8, 23.8, 22.7, 18.3, 18.2, 16.7, 14.1, 13.6, 13.4; ESIMS: calcd for
[M+Na]+ m/z 1540.8; found: 1541.2.
½
a 2D2
ꢂ
ꢀ12.6 (c 0.07, CHCl3); 1H NMR (600 MHz, CDCl3): d 7.76 (d,
1H, J 7.7 Hz, Ph), 7.49–6.97 (m, 33H, Ph), 5.07 (t, 1H J 9.4 Hz, H-
30), 5.04 (d, 1H, J 12.6 Hz, PhCH2), 4.96 (d, 1H, J 12.1 Hz, PhCH2),
4.93 (t, 1H J 9.8 Hz, H-40), 4.87 (d, 1H, J 11.7 Hz, PhCH2), 4.85 (d,
1H, J 11.2 Hz, PhCH2), 4.78 (d, 1H, J 11.5 Hz, PhCH2), 4.72–4.69
(m, 3H, H-10 and PhCH2), 4.55 (d, 1H, J 12.1 Hz, PhCH2), 4.53 (d,
1H, J 10.4 Hz, PhCH2), 4.49 (d, 1H, J 12.1 Hz, PhCH2), 4.44 (d, 1H, J
10.6 Hz, PhCH2), 4.42 (d, 1H, J 6.6 Hz, H-1), 4.34 (d, 1H, J 12.1 Hz,
PhCH2), 3.99–3.97 (m, 1H, H-50), 3.84 (s, 1H, H-100), 3.73–3.49 (m,
9H, H-20, H-4, H-6, H-500, H-60, H-3, H-200, H-300, H-400), 3.45–3.31
(m, 3H, H-2, H-5 and OCH), 2.36 (t, 2H, J 7.70 Hz, COCH2), 2.24–
2.20 (m, 4H, 2 ꢃ COCH2), 2.04 (s, 3H, COCH3), 1.67–1.22 (m, 35H,
2 ꢃ CH2CH2CO, 14 ꢃ CH2 and 600-Me); 0.92–0.87 (m, 9H, 3 ꢃ CH3);
13C NMR (150 MHz, CDCl3): d 209.2, 173.2, 172.7, 166.1, 139.6,
139.2, 138.4, 138.3, 138.0, 137.9, 128.6–127.2, 102.8, 102.3,
101.0, 84.8, 80.0, 79.9, 79.0, 78.8, 76.2, 74.9, 74.2, 74.0, 73.7, 73.6,
73.3, 71.9, 70.5, 69.0, 68.6, 66.2, 60.5, 43.9, 36.3, 36.1, 34.7, 33.9,
30.0–29.3, 25.3, 23.9, 22.8, 18.5, 18.4, 14.3, 14.2, 13.7. ESIMS: calcd
for [M+Na]+ m/z 1471.8; found:1471.8.
3.23. (10R)-2-Nonadecanone-10-yl 2,3,4-tri-O-benzyl-6-deoxy-
3.25. (10R)-2-Nonadecanone-10-yl 2,3,4-tri-O-benzyl-6-deoxy-
b-
di-O-butyryl-b-
glucopyranoside (31)
D
-talopyranosyl-(1?6)-2-O-[(2-O-azidomethyl)benzoyl]-3,4-
a
-
L
-glucopyranosyl-(1?2)- [2,3,4-tri-O-benzyl-6-deoxy-b-
talopyranosyl-(1?6)]-3,4-di-O-butyryl-b- -glucopyranosyl-
(1?2)-3,4,6-tri-O-benzyl-b- -glucopyranoside (36)
D-
D
-glucopyranosyl-(1?2)-3,4,6-tri-O-benzyl-b-
D-
D
D
To a solution of 30 (99.0 mg, 0.06 mmol), BnO(CCl3)C@NH
To a mixture of 32 (20.0 mg, 0.01 mmol), 4 (15.0 mg,
(100 mg, 0.30 mmol), 4 Å molecular sieves in dry CH2Cl2 (3 mL),
and cyclohexane (3 mL), TfOH (5 lL) was added at room tempera-
0.02 mmol), and 4 Å molecular sieves in dry CH2Cl2 (3 mL), NIS
(4.0 mg, 0.016 mmol) and AgOTf (1.0 mg, 0.002 mmol) were added
at 0 °C under argon. The reaction mixture was stirred for an addi-
tional 12 h while allowed to warm to room temperature. After the
reaction was complete as judged by TLC, the reaction mixture was
filtered and concentrated. Then the residue was diluted with
CH2Cl2 (20 mL), and washed with 10% aq Na2S2O3 (15 mL), aq NaH-
CO3 (15 mL), and brine (2 ꢃ 15 mL). The organic layer was dried
over Na2SO4, filtered, and concentrated. The residue was purified
by silica gel column chromatography (6:1 petroleum ether–EtOAc)
to give 36 (6.0 mg, 23%) as a syrup: Rf 0.55 (3:1 petroleum ether–
ture under argon. The reaction mixture was stirred under these
conditions for 1 h, then neutralized with Et3N (two drops). The so-
lid was filtered off, and the filtrate was concentrated under dimin-
ished pressure. The resulting residue was purified by silica gel
column chromatography (4:1, petroleum ether–EtOAc) to give 31
(108.9 mg, 79%) as a syrup: Rf 0.40 (4:1 petroleum ether–EtOAc);
½
a 2D0
ꢂ
ꢀ7.0 (c 0.1, CHCl3); 1H NMR (600 MHz, CDCl3): d 7.76 (d, 1H,
J 7.7 Hz, Ph), 7.49–6.97 (m, 33H, Ph), 5.33 (t, 1H J 9.4 Hz, H-30),
5.21–5.16 (m, 2H, H-10 and H-20), 5.07 (d, 1H, J 12.7 Hz, PhCH2),
4.99 (d, 1H, J 12.1 Hz, PhCH2), 4.94 (t, 1H J 9.9 Hz, H-40), 4.85 (d,
1H, J 14.3 Hz, PhCH2), 4.78 (d, 2H, J 12.1 Hz, PhCH2), 4.64 (d, 1H, J
14.3 Hz, PhCH2), 4.61–4.36 (m, 9H, PhCH2 and H-6a0), 4.30 (d, 1H,
J 7.13 Hz, H-1), 4.02 (s, 1H, H-100), 3.94–3.90 (m, 1H, H-6b0), 3.69–
3.31 (m, 12H, H-2, H-3, H-4, H-5, H-6a, H-6b, H-50, H-200, H-300, H-
400, H-500 and OCH), 2.35 (t, 2H, J 7.70 Hz, COCH2), 2.27–2.23 (m,
2H, COCH2), 2.15–2.12 (m, 2H, COCH2), 2.10 (s, 3H, COCH3), 1.67–
1.22 (m, 35H, 2 ꢃ CH2CH2CO, 14 ꢃ CH2 and 600- Me), 0.94–0.86
(m, 6H, 2 ꢃ CH3), 0.74 (t, 3H, J 7.4 Hz, CH3). 13C NMR (150 MHz,
CDCl3): 206.9, 172.7, 172.2, 164.7, 139.6, 138.5, 138.1, 138.0,
137.7, 137.4, 132.8, 130.8, 129.8, 128.5–126.9, 102.4, 101.5, 99.5,
85.8, 81.0, 78.7, 77.7, 75.0, 74.7, 74.6, 74.3, 73.7, 73.2, 72.5, 72.4,
EtOAc); mp 149.1–150.0 °C ½a D22
ꢂ
ꢀ15.7 (c 0.2, CHCl3); 1H NMR
(600 MHz, CDCl3): d 7.46–7.04 (m, 45 H), 5.29 (t, 1H, J 9.3, 7.7 Hz,
H-30), 5.23 (d, 1H, J 3.3 Hz, H-1000), 5.14 (d, 1H, J 11.5 Hz, PhCH2),
5.13 (t, 1H J 8.3 Hz, H-40), 5.03–4.63 (m, 17 H, H-10, H-20 and
7 ꢃ PhCH2), 4.60 (d, 1H, J 11.5 Hz, PhCH2), 4.55 (d, 1H, J 10.4 Hz,
PhCH2), 4.54 (d, 1H, J 11.0 Hz, PhCH2), 4.50 (d, 1H, J 11.0 Hz,
PhCH2), 4.44–4.42 (m, 1H, H-6a0), 4.37–4.32 (m, 1H, H-6b0), 4.25
(d, 1H, J 7.7 Hz, H-1), 4.07 (t, 1H, J 9.3 Hz, H-4), 3.98 (s, 1H, H-100),
3.81–3.77 (m, 2H, H-3 and H-50), 3.74 (t, 1H, J 8.8 Hz, H-2), 3.56–
3.37 (m, 10H, H-6, H-5, H-200, H-300, H-400, H-2000, H-3000, H-4000, H-500
and OCH), 3.29–3.26 (m, 1H, H-5000), 3.16 (dd, 1H, J = 9.4, 8.8 Hz,
H-4000), 2.36–2.32 (m, 2H, COCH2), 2.23–2.13 (m, 4H, 2 ꢃ COCH2),

760
Z. Zhang et al. / Carbohydrate Research 345 (2010) 750–760
2.09 (s, 3H, COCH3), 1.65–1.18 (m, 37H, 2 ꢃ CH2CH2CO, 14 ꢃ CH2,
600-Me and 6000-Me); 0.94–0.83 (m, 9H, 3 ꢃ CH3); 13C NMR
(150 MHz, CDCl3): 172.5 172.2, 139.7, 139.4, 138.7–137.8, 128.6–
126.9, 102.4, 102.1, 99.6, 96.2, 91.1, 86.5, 84.4, 83.7, 83.5, 82.2,
81.7, 81.5, 80.3, 78.9, 75.7–73.2, 72.6, 71.6, 70.5, 69.8, 69.2, 68.1,
67.0, 66.9, 43.7, 36.2, 35.8, 35.1, 34.3, 31.9, 30.1–29.2, 25.3, 25.0,
23.8, 22.7, 18.2, 18.0, 14.1, 13.7, 13.6; ESIMS: calcd for [M+H]+ m/
z 1867.0; found: 1867.6; HRESIMS: m/z calcd for C34H30O7SNa+
605.1610; found 605.1602.
Acknowledgments
This work was supported by a grant from the Ph.D. Programs
Foundation of Ministry of Education of China (No. 20070423001)
and the National Natural Science Youth Foundation (No.
30701046).
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.01.015.
3.26. (10R)-2-Nonadecanone-10-yl 6-deoxy-
(1?2)-[6-deoxy-b- -talopyranosyl-(1?6)]- 3,4-di-O-butyryl-b-
glucopyranosyl-(1?2)-b- -glucopyranoside (1)
a-L-glucopyranosyl-
D
D-
D
References
Compound 36 (6 mg) was dissolved in MeOH (5 mL) and then
10%-Pd/C (50 mg) was added. After stirring at 50 °C for 4 h under
H2, the mixture was filtered through a Celite pad and the filtrate
was concentrated. The resulting residue was subjected to Sephadex
LH-20 chromatography (1:1 MeOH–CH2Cl2) to yield 1 (3.0 mg,
88%) as a colorless glass: Rf 0.33 (2:1 CHCl3–CH3OH-1% AcOH);
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½
a 2D5
ꢂ
ꢀ24 (c 0.175, MeOH), (Lit.4b
½
a 2D5
ꢂ
ꢀ22 (c 0.17, MeOH); 1HNMR
(600 MHz, DMSO-d6): d 5.17 (t, 1H, J 10.2 Hz, H-30), 5.04 (d, 1H, J
7.7 Hz, H-10), 4.63 (s, 2H, H-100 and H-1000), 4.57 (t, 1H, J 9.9 Hz, H-
40),4.39–4.37 (m, 3H, 3 ꢃ OH), 4.22(t, 1H, J 6.8, 6.4 Hz, 6-OH),
4.13 (d, 1H, J 6.8 Hz, H-1), 4.01–3.95 (m, 1H, H-5000), 3.90–3.85
(m, 1H, OH), 3.68–3.57 (m, 4H, H-6a, H-6a0, H-50 and OCH), 3.50–
3.30 (m, 8H, H-6b, H-6b0, H-200, H-300, H-400, H-500, H-20, H-3000),
3.16–3.11 (m, 2H, H-2000 and H-4), 3.03–2.99 (m, 1H, H-5), 2.94 (t,
1H, J 9.6 Hz, H-3), 2.71 (t, 1H, J 9.3 Hz, H-4000), 2.39 (t, 2H, J 7.7 Hz,
COCH2), 2.34–2.12 (m, 4H, 2 ꢃ COCH2), 2.05 (s, 3H, COCH3), 1.68–
1.18 (m, 32H, 2 ꢃ CH2CH2CO and 14 ꢃ CH2); 1.14 (d, 3H, J 6.4 Hz,
600-Me), 1.09 (d, 3H, J 5.9 Hz, 6000-Me), 0.84 (t, 9H, J 7.8 Hz,
3 ꢃ CH3); 13C NMR (150 MHz, DMSO-d6): d 208.4, 171.8, 171.4,
101.4, 101.2, 100.0, 99.4, 80.8, 77.0, 76.9, 76.5, 75.6, 73.6, 73.3,
72.6, 72.3, 72.0, 71.8, 71.3, 70.7, 69.9, 69.5, 68.3, 67.2, 60.6, 42.6,
35.3, 35.0, 34.2, 33.7, 31.3, 29.7–28.5, 23.1, 22.1, 17.9, 17.6, 17.5,
16.4, 13.8, 13.3, 13.2. ESIMS: calcd for [M+Na]+ m/z 1077.6;
found:1077.7. HRESIMS: m/z calcd for C51H90O22Na+ 1077.5821;
found 1077.5853.
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2007, 63, 2571–2592.
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1
(Lit.4b HNMR (800 MHz, DMSO-d6): d 5.17 (H-30), 5.04 (H-10),
4.65 (H-1000) 4.64 (H-100), 4.57 (H-40), 4.13 (H-1), 3.92 (H-5000), 3.66
(H-50), 3.64 (H-200), 3.63 (H-6a0) 3.62 (H-6a) 3.44 (OCH), 3.48 (H-
6b), 3.42 (H-6b0), 3.40 (H-20), 3.39 (H-500), 3.34 (H-3000), 3.16 (H-4),
3.13 (H-2000), 3.03 (H-5), 2.75 (H-4000), 2.37 (COCH2), 2.27
(2 ꢃ COCH2), 2.04 (COCH3), 1.47 (2 ꢃ CH2CH2CO), 1.19 (CH2), 1.13
(d, 3H, J = 6.4 Hz, 600-Me), 1.08 (6000-Me), 0.84, (2 ꢃ CH3) 0.83
(CH3); 13C NMR (100 MHz, DMSO-d6): d 208.0, 171.5, 171.0,
101.2, 101.0, 99.7, 99.2, 80.8, 77.1, 77.0, 76.5, 75.6, 73.7, 73.4,
72.6, 72.1, 71.7, 71.3, 70.9, 69.9, 69.5, 68.4, 67.0, 60.7, 42.7, 35.4,
35.1, 34.3, 33.7, 29.7, 29.6, 29.5, 29.3, 29.1, 29.0, 28.8, 28.7, 28.5,
23.0, 17.9, 17.6, 17.5, 16.4, 13.9, 13.4, 13.3.)