Total synthesis of cleistetroside-2, partially acetylated dodecanyl tetrarhamnoside derivative isolated from Cleistopholis patens and Cleistopholis glauca

Article abstract of DOI:10.1016/j.carres.2007.03.014

The total synthesis of a partially acetylated dodecanyl tetrarhamnoside derivative, cleistetroside-2, which was isolated from Cleistopholis patens and Cleistopholis glauca and showed significant in vitro antibacterial activity against the Gram-positive ba

Full text of DOI:10.1016/j.carres.2007.03.014

Carbohydrate Research 342 (2007) 1159–1168
Total synthesis of cleistetroside-2, partially acetylated
dodecanyl tetrarhamnoside derivative isolated from
Cleistopholis patens and Cleistopholis glauca
Zaihong Zhang, Peng Wang, Ning Ding, Gaopeng Song and Yingxia Li*
Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Pharmacy, Ocean University of China,
Qingdao 266003, China
Received 10 January 2007; received in revised form 8 March 2007; accepted 9 March 2007
Available online 16 March 2007
Abstract—The total synthesis of a partially acetylated dodecanyl tetrarhamnoside derivative, cleistetroside-2, which was isolated
from Cleistopholis patens and Cleistopholis glauca and showed significant in vitro antibacterial activity against the Gram-positive
bacteria, was achieved for the first time.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Cleistetroside; Oligorhamnoside; Antibacterial; Gram-positive bacteria; Synthesis
1. Introduction
their associated biosynthetic pathways could be targets
for the development of novel inhibitors of mycobacterial
cell wall elaboration.
The rising incidence of infections caused by antibiotic-
resistant bacteria has become a major concern for clini-
cians and the public health system. In the past several
years, these types of infections have increased in sever-
ity, and their treatment has become far more complex
and costly.1,2 Therefore, searching for novel classes of
antibiotics is critically important in order to effectively
combat these and other complex antibiotic-resistant
pathogens.3 Carbohydrates are the most abundant
species among the biopolymers and have recently been
actively studied as important biological molecules.4 It
has been shown that the oligosaccharides have the abil-
ity to control the microbial infection.5,6 The identifica-
tion of the mycobacterial cell wall polysaccharides and
the monosaccharides contained therein (particularly
arabinofuranose, galactofuranose, and rhamnopyranose
residue)7 has focused interest on the putative glycos-
yltransferases required for biosynthesis.8 These particu-
lar sugar units are not found in mammalian cells and
As part of high-throughput natural products program
directed toward the discovery of novel antibacterial
agents from plants,9 eight partially acetylated oligo-
rhamnosides with significant in vitro antibacterial
activity have been obtained recently from Cleistopholis
patens by the Hu group.10 One of the oligorhamnoside
derivatives, cleistetroside-2 (1, Scheme 1), initially iso-
´
lated from the species Cleistopholis glauca by Tane
et al.11 in 1988 and subsequently found in C. patens by
Waterman group12 in 1999, showed the best in vitro
antibacterial activity against the Gram-positive bacteria
methicillin resistant Staphylococcus aureus ATCC 33591
and S. aureus 78-13607A with MICs of 61 lg/mL.10
Furthermore, it showed significant in vitro antibacterial
activity against an expanded panel of Gram-positive
pathogens including either ATCC strains or well-charac-
terized clinical isolates from the global SENTRY
Antimicrobial Surveillance Program.10 Therefore a
synthesis-driven mapping of their structure/activity pro-
file is called for to probe these promising and diverse
biological effects of partially acetylated oligorhamno-
sides in more detail. In this paper, we would like to
*
Corresponding author. Tel.: +86 532 82032150; fax: +86 532
82033054; e-mail: liyx417@ouc.edu.cn
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.03.014

1160
Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
STol
OC12H25
OC12H25
OC12H25
O
O
O
O
HO
AcO
O
O
O
O
O
O
RO
AcO
O
OLev
HO
OH
HO
O
OLev
AcO
4
5 R=TBS
6 R=PMB
2
O
OH
NH
O
STol
AcO
STol
O
O
O
CCl3
OAc
AcO
O
O
O
AcO
AcO
O
AcO
OAc
HO
O
HO
O
OAc
OH
AcO
O
O
7
1 Cleistetroside-2
8
O
3
Scheme 1. Retrosynthetic analysis of cleistetroside-2.
report a facile synthesis of this partially acetylated
dodecanyl tetrarhamnoside derivative cleistetroside-2,
which would provide a facile approach to other struc-
tural analogues.
5 or 6. While building block 3 as a glycosyl donor could
be easily obtained by condensation of 2,4-di-O-acetyl
acceptor 7 with trichloroacetimidate donor 8. Although
b-glycoside formation was observed occasionally, the
good a-stereoselectivity in the glycosylation of rhamno-
pyranosyl donors that were either glycosylated at C-2 or
blocked at this position with a non-participating group
has been reported on several occasions in the litera-
ture.13 Thus, we designed donor 8 with a non-participat-
ing isopropylidene group at C-2 and C-3.
2. Results and discussion
The four acetyl groups in cleistetroside-2 require atten-
tion in the convergent synthesis due to their O to O
migration in some acidic or basic conditions. To address
this issue, we chose isopropylidene and levulinoyl
groups as hydroxy protecting groups, which could be
selectively removed without affecting acetyl groups
under mild conditions. Therefore the target compound
1 was retrosynthesized into two disaccharide building
blocks 2 and 3 (Scheme 1). Building block 2 as a glycosyl
acceptor could be derived from the glycosylation of
monosaccharide acceptor 4 with monosaccharide donor
First of all, building block 2 was synthesized by cou-
pling of acceptor 4 with donor 5 or 6. As outlined in
Scheme 2, starting from readily available L-rhamnopyr-
anosyl tetraacetate 9,14 the glycosylation with n-dodecyl
15
alcohol using SnCl4 as a catalyst was carried out
smoothly to give pure a-isomer 10 in 70% yield. We
had tried the glycosidic coupling of p-tolyl 2,3,4-tri-O-
acetyl-1-thio-a-L-rhamnopyranoside or 2,3,4-tri-O-acet-
yl-a-L-rhamnopyranosyl trichloroacetimidate under the
OC12H25
O
O
OC12H25
O
OC H25
12
O
O
AcO
OAc
a
O
b
O
O
HO
AcO
STol
HO
15
AcO
OH
O
AcO
10
AcO
O
OAc
OAc
OC12H25
g
9
4
O
f
O
O
O
O
AcO
STol
STol
STol
TBSO
OLev
h
e
d
O
O
O
c
AcO
TBSO
O
14
AcO
AcO
AcO
HO
12
O
TBSO
13
OLev
OH
OH
OC12H25
O
5
O
11
O
HO
OH
O
AcO
TBSO
16
OLev
Scheme 2. Reagents and conditions: (a) C12H25OH, CH3CN, SnCl4, 69.8%; (b) (i) NaOMe, MeOH; (ii) 2,2-dimethoxylproprane, p-TsOH, DMF,
88.8% for two steps; (c) 80% HOAc, 93.1%; (d) TBSCl, imidazole, DMAP, pyridine, 99.0%; (e) levulinic acid, DCC, DMAP, CH2Cl2, 83.9%; (f) NIS,
AgOTf, CH2Cl2, 83.4%; (g) TBAF, THF, 45.0%; (h) HFÆpyridine, THF, 11.6%.

Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
1161
promotion of NIS/AgOTf, NIS/TfOH, trimethylsilyl
trifluoromethanesulfonate (TMSOTf), BF3ÆEt2O or
AgOTf, respectively, but compound 10 was not ob-
tained in an acceptable yield. Removal of the acetyl
groups in 10 with NaOMe in MeOH, followed by pro-
tecting the corresponding 2,3-positions with an isopro-
pylidene group provided acceptor 4 (1JC-1,H-1 = 167.5
Hz) in 89% good yield for two steps.
to afford p-tolyl 4-O-acetyl-3-O-PMB-1-thio-a-L-
rhamnopyranoside 17 in a favorable yield (74%). But
employing toluene–MeOH as solvent diol 12 was con-
verted to side product 18 due to removal of the acetyl
group27 in C-4–OH. Then treatment of compound 17
under the conditions for 5 gave levulinoyl ester 6 in an
acceptable yield (57%). Glycosylation of donor 6 with
acceptor 4 produced disaccharide 19 in an excellent yield
(97%). And the a-configuration of the new glycosidic
bond in 19 was confirmed by the HMBC spectrum
We first designed donor 5 with a tert-butyldimethylsi-
lyl (TBS) group at C-3–OH for the construction of build-
ing block 2. Thus, the known thioglycoside 1116 was
subjected to removal of the 2,3-O-isopropylidene group
(80% HOAc, 80 ꢁC) to produce diol 12 (93%), which sub-
sequently was silylated with tert-butyldimethylsilyl chlo-
ride in the presence of imidazole in pyridine (rt) to give
an excellent yield of monosilylated compound 13 regiose-
lectively (99%). It is worth noting that the high regiose-
lectivity of the monosilylation was achieved only when
pyridine was chosen as solvent in our experiment. Reac-
tion of 13 with levulinic acid (LevOH) in the presence of
N,N0-dicyclohexylcarbodiimide (DCC) and 4-N,N-dim-
ethylaminopyridine (DMAP)17 afforded the desired do-
nor 5 in a good yield (84%). Regioselective substitution
on C-3–OH of 13 was further confirmed from its levuli-
noyl ester 5, that is, the chemical shifts of H-2 in 5 moved
downfield to 5.32 ppm, from around 3.92 ppm in 13. Fi-
nally, coupling of donor 5 with acceptor 4 was carried
out in the presence of NIS and AgOTf to provide disac-
charide 14 in 84% yield. However, removal of the silyl
ether group from 14 by the usual reagent, 1.0 equiv
TBAF in THF,18 resulted in cleavage of the levulinoyl es-
ter bond and formed side product 15 in 45% yield. When
the deprotection was performed with HFÆpyridine in
THF,19 leading to another side product 16 because of
the lability of isopropylidene group to the acid condition.
We had also examined other conditions for the desilyla-
tion, such as BF3ÆEt2O,20 pyridinium p-toluenesulfonate
(PPTS),21 TBAF-HOAc-THF,22 Pd(MeCN)2Cl2,23
TMSCI-KFÆ2H2O,24 and 2.3-dichloro-5,6-dicyanobenz-
oquinone (DDQ).25 Unfortunately, they all failed to
provide the desired building block 2.
(1JC-1 ,H-1 = 171.8 Hz). To our delight, deprotection of
the 30-O-PMB group with DDQ was conducted readily
to form our expected building block 2 in 85% yield.
The next effort was to construct disaccharide building
block 3, which could be readily obtained by glycosyla-
tion of monosaccharide acceptor 7 with donor 8
(Scheme 4). Acceptor 7 was prepared from compound
20 in a simple one-pot method.28 Treatment of 20 with
triethylorthoacetate and a catalytic amount of (1S)-
(+)-camphor-10-sulfonic acid (CSA) formed the corre-
sponding orthoesters, which were directly acetylated in
the same pot to protect the remaining hydroxy group.
Then the reaction mixture was diluted with dichloro-
methane and shaken with 1 M HCl solution to effect
orthoester rearrangement, giving the expected com-
pound 7 in high yield (72%). And donor 8 was synthe-
sized from thioglycoside 11 in two steps. Hydrolysis of
11 with N-bromosuccinimide (NBS) in acetone–H2O,
followed by treatment with CCl3CN and 1,8-diazabicy-
clo[5.4.0]undec-7-ene (DBU) gave trichloroacetimidate
8 in 73% yield for two steps. Then, donor 8 was coupled
with acceptor 7 using TMSOTf as promoter to provide
desired building block 3 in an excellent yield (99%).
With the acceptor 2 and donor 3 in hand, an NIS/
AgOTf-promoted coupling was carried out to afford
tetrasaccharide 21 in 62% good yield. Finally, deprotec-
tion of the Lev group with hydrazine acetate (82%) and
the isopropylidene group with 80% HOAc (83%)
smoothly furnished the target cleistetroside-2 (1). The
physical data obtained were full in agreement with those
reported for the natural product.
0
0
Alternatively we designed another monosaccharide
donor 6 with a p-methoxybenzyl (PMB) group at C-3–
OH. In Scheme 3: Diol 12 was refluxed with Bu2SnO
in toluene,26 followed by reaction with p-methoxybenzyl
chloride in the presence of CsF, and Bu4NI in DMF (rt)
In conclusion, we have successfully synthesized the
partially acetylated dodecanyl tetrarhamnoside deriva-
tive cleistetroside-2 in a convergent approach. The syn-
theses of its analogues and their bioactivities will be
reported later.
OC12H25
d
OC12H25
STol
STol
STol
O
O
b
a
c
O
O
O
O
AcO
O
AcO
PMBO
RO
PMBO
O
O
O
O
O
O
HO
AcO
PMBO
19
AcO
OLev
OH
OH
HO
17 R=Ac
18 R=H
6
OLev
OLev
12
2
Scheme 3. Reagents and conditions: (a) (i) Bu2SnO, toluene; (ii) p-methoxybenzyl chloride, TBAI, DMF, 74.1% for two steps; (b) levulinic acid,
DCC, DMAP, CH2Cl2, 56.9%; (c) NIS, AgOTf, CH2Cl2, 96.7%; (d) DDQ, CH2Cl2–MeOH, 85.0%.

1162
Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
STol
STol
STol
STol
a
O
O
O
HO
H3C
AcO
H3C
O
HO
AcO
STol
O
O
HO
20
O
HO
7
O
OH
OAc
NH
O
AcO
OEt
OEt
b
O
OAc
O
O
O
CCl3
AcO
f
O
O
O
11
AcO
O
3
8
OC12H25
OC12H25
O
O
O
O
O
O
O
O
O
O
AcO
AcO
2
c
e
d
1
O
O
OH
OLev
O
O
AcO
AcO
O
O
OAc
OAc
O
O
AcO
AcO
O
O
O
O
21
22
Scheme 4. Reagents and conditions: (a) (i) MeC(OEt)3, CSA, DMF; (ii) Ac2O, DMAP, TEA, pyridine; (iii) 1 M HCl, 71.5% for three steps; (b)
TMSOTf, CH2Cl2, 99.0%; (c) NIS, AgOTf, CH2Cl2, 61.6%; (d) hydrazine acetate, CH2Cl2–MeOH, 82.1%; (e) 80% HOAc, 82.7%; (f) (i) NBS,
acetone–H2O; (ii) DBU, CNCCl3, CH2Cl2, 73.4% for two steps.
3. Experimental
3.1. General methods
satd aq NaHCO3 (3 · 100 mL), brine (2 · 100 mL),
dried over Na2SO4, filtered, and concentrated in vacuo.
The resulting crude oil was purified via silica gel column
chromatography (10:1, petroleum ether–EtOAc) to yield
10 (8.90 g, 69.8%) as a colorless oil: Rf 0.53 (4:1, petro-
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 polar-
imeter. 1H NMR and 13C NMR spectra were taken on a
JEOL JNM-ECP 600 spectrometer with tetramethyl-
silane as the internal standard, and chemical shifts are
recorded in d values. Mass spectra were recorded on a
Q-TOF Global mass spectrometer.
20
leum ether–EtOAc); ½aꢀD ꢁ48.7 (c 0.10, CHCl3); 1H
NMR (CDCl3) d 5.30 (dd, 1H, J = 10.1, 3.7 Hz, H-3),
5.23 (dd, 1H, J = 3.7, 1.9 Hz, H-2), 5.06 (t, 1H,
J = 9.9 Hz, H-4), 4.71 (d, 1H, J = 1.4 Hz, H-1), 3.9–
3.85 (m, 1H, H-5), 3.68–3.64 (m, 1H, OCHH), 3.43–
3.40 (m, 1H, OCHH), 2.15 (s, 3H, COCH3), 2.05 (s,
3H, COCH3), 1.99 (s, 3H, COCH3), 1.63–1.56 (m, 2H,
bCH2), 1.33–1.30 (m, 2H, cCH2), 1.28 (br s, 16H,
(CH2)8), 1.22 (d, 3H, J = 6.0 Hz, CH3-6), 0.88 (t, 3H,
J = 7.1 Hz, CH3); 13C NMR (CDCl3) d 170.2, 170.0,
169.9, 97.4, 71.2, 70.0, 69.1, 68.2, 66.1, 31.9, 30.9,
29.7–29.3, 26.0, 22.6, 20.9, 20.8, 20.7, 17.4, 14.1. ESIMS:
calcd for [M+Na]+ m/z 481.3; found: m/z 481.2.
3.2. 1-O-Dodecanyl-2,3,4-tri-O-acetyl-a-L-rhamno-
pyranoside (10)
To a solution of compound 9 (12.0 g, 36.1 mmol) in dry
CH3CN (100 mL) was added SnCl4 (3.9 mL, 33.3 mmol)
at 0 ꢁC and the mixture was stirred for 30 min. To the
cold solution, a n-dodecanol (5.2 g, 27.8 mmol) solution
in CH3CN was added dropwise over a period of 30 min.
The reaction was stirred for an additional 30 min while
warming to room temperature. After the reaction was
completed as judged by TLC, the reaction was quenched
with water (50 mL) and extracted with CHCl3
(2 · 200 mL). The chloroform layer was washed with
3.3. 1-O-Dodecanyl-2,3-O-isopropylidene-a-L-rhamno-
pyranoside (4)
To a dry methanolic solution (25 mL) of compound 10
(1.66 g, 3.6 mmol) was added NaOMe (26.7 mg) at
0 ꢁC. The reaction mixture was stirred at room temper-
ature for 30 min, after which the reaction mixture was
neutralized with Dowex 50 · 8(H+) resin until pH 7, fil-
tered and concentrated. The residue was dried under
vacuum to give a crude product. To a solution of the

Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
1163
crude product (1.17 g, 3.5 mmol) in dry DMF (10 mL)
were added 2,2-dimethoxypropane (1.3 mL, 10.5 mmol)
and p-toluenesulfonic acid (66.9 mg, 0.4 mmol) at room
temperature. After 13 h stirring, Et3N was added drop-
wise to attain pH 7.0. The solution was concentrated in
vacuo. The resulting crude product via silica gel column
chromatography (10:1, petroleum ether–EtOAc) gave 4
(1.16 g, 88.8% for two steps) as a white solid: Rf 0.50
a colorless oil: Rf 0.5 (4:1, petroleum ether–EtOAc);
20
1
½aꢀD ꢁ171.5 (c 0.10, CHCl3); H NMR (DMSO-d6) d
7.34 (d, 2H, J = 7.8 Hz, Ph), 7.17 (d, 2H, J = 7.8 Hz,
Ph), 5.45 (d, 1H, J = 4.6 Hz, 2-OH), 5.29 (d, 1H,
J = 1.4 Hz, H-1), 4.94 (t, 1H, J = 9.6 Hz, H-4), 4.07–
4.02 (m, 1H, H-5), 3.92 (br s, 1H, H-2), 3.84 (dd, 1H,
J = 9.6, 3.2 Hz, H-3), 2.28 (s, 3H, PhCH3), 2.05 (s,
3H, COCH3), 1.05 (d, 3H, J = 6.0 Hz, CH3-6), 0.85 (s,
9H, (CH3)3C), 0.07 (s, 3H, CH3), 0.05 (s, 3H, CH3);
13C NMR (CDCl3) d 169.9, 137.7, 131.8, 129.9, 86.9,
73.8, 72.9, 70.9, 67.3, 25.5, 21.1, 21.0, 17.8, 17.3. ESIMS:
calcd for [M+Na]+ m/z 449.2; found: m/z 449.1.
20
(3:1, petroleum ether–EtOAc); ½aꢀD ꢁ25.5 (c 0.10,
CHCl3); 1H NMR (DMSO-d6)
d 5.20 (d, 1H,
J = 6.4 Hz, 4-OH), 4.86 (s, 1H, H-1), 4.02 (d, 1H,
J = 5.9 Hz, H-2), 3.84 (dd, 1H, J = 7.4, 5.5 Hz, H-3),
3.57 (td, 1H, J = 9.7, 6.4 Hz, H-4), 3.43–3.36 (m, 2H,
H-5 and OCHH), 3.07–3.03 (m, 1H, OCHH), 1.53–
1.48 (m, 2H, O CH2), 1.40 (s, 3H, CH3), 1.26 (s, 3H,
CH3), 1.24 (s, 16H, (CH2)8), 1.12 (d, 3H, J = 6.0 Hz,
CH3-6), 0.85 (t, 3H, J = 7.1 Hz, CH3); 13C NMR
(DMSO-d6) d 108.1, 96.2, 78.1, 75.5, 73.4, 66.6, 65.5,
31.3, 29.0–28.7, 28.0, 26.2, 25.6, 22.1, 17.4, 13.9. ESIMS:
calcd for [M+Na]+ m/z 395.3; found: m/z 395.3.
3.6. p-Tolyl 4-O-acetyl-3-O-tert-butyldimethylsilyl-2-O-
levulinoyl-1-thio-a-L-rhamnopyranoside (5)
To a solution of compound 13 (0.5 g, 1.2 mmol) in dry
CH2Cl2 (10 mL), levulinic acid (272.0 mg, 2.4 mmol),
DCC (484.1 mg, 2.4 mmol), and DMAP (14.3 mg,
0.12 mmol) were added under argon. The mixture was
stirred for 12 h, diluted with CH2Cl2 (100 mL), washed
with H2O (50 mL), 1 M HCl (2 · 50 mL), satd aq NaH-
CO3 (2 · 50 mL), and brine (2 · 50 mL), dried over
Na2SO4, and concentrated. The residue was purified by
silica gel column chromatography (10:1, petroleum
ether–EtOAc) to give 5 (516.0 mg, 83.9%) as a syrup:
3.4. p-Tolyl 4-O-acetyl-1-thio-a-L-rhamnopyranoside (12)
Compound 11 (6.2 g, 18.5 mmol) was dissolved in 80%
HOAc (80 mL) and stirred for 1.5 h at 80 ꢁC, then the
reaction mixture was concentrated. The residue was
purified by silica gel column chromatography (10:1,
CHCl3–MeOH) to give compound 12 (5.36 g, 93.1%)
as a white solid: Rf 0.5 (1:2, petroleum ether–EtOAc);
20
Rf 0.57 (3:1, petroleum ether–EtOAc); ½aꢀD ꢁ68.9 (c
0.10, CHCl3); 1H NMR (CDCl3) d 7.34 (d, 2H,
J = 8.2 Hz, Ph), 7.12 (d, 2H, J = 8.2 Hz, Ph), 5.32 (dd,
1H, J = 3.2, 1.4 Hz, H-2), 5.30 (s, 1H, H-1), 5.02 (t,
1H, J = 9.7 Hz, H-4), 4.27–4.22 (m, 1H, H-5), 4.04 (dd,
1H, J = 9.6, 3.7 Hz, H-3), 2.79–2.62 (m, 4H,
COCH2CH2CO), 2.33 (s, 3H, PhCH3), 2.19 (s, 3H,
COCH3), 2.10 (s, 3H, COCH3), 1.21 (d, 3H,
J = 6.4 Hz, CH3-6), 0.84 (s, 9H, (CH3)3C), 0.09, (s, 6H,
2CH3); 13C NMR (CDCl3) d 206.1, 171.8, 169.8, 138.0,
132.2, 129.9, 129.7, 86.2, 74.0, 73.8, 68.9, 67.7, 37.8,
30.9, 29.8, 28.0, 25.6, 25.4, 21.1, 21.0, 17.8, 17.4. ESIMS:
calcd for [M+Na]+ m/z 547.2; found: m/z 547.1.
20
1
½aꢀD ꢁ273.6 (c 0.10, CHCl3); H NMR (DMSO-d6) d
7.34 (d, 2H, J = 8.0 Hz, Ph), 7.17 (d, 2H, J = 8.0 Hz,
Ph), 5.44 (d, 1H, J = 4.1 Hz, 2-OH), 5.29 (s, 1H, H-1),
5.09 (d, 1H, J = 6.0 Hz, 3-OH), 4.86 (t, 1H,
J = 9.6 Hz, H-4), 4.06–4.01 (m, 1H, H-5), 3.94 (ddd,
1H, J = 4.6, 2.8, 1.4 Hz, H-2), 3.65 (ddd, 1H, J = 9.6,
5.9, 3.2 Hz, H-3), 2.29 (s, 3H, PhCH3), 2.06 (s, 3H,
COCH3), 1.04 (d, 3H, J = 6.0 Hz, CH3-6); 13C NMR
(DMSO-d6) d 169.9, 137.0, 131.6, 130.2, 129.8, 88.6,
73.8, 71.8, 68.8, 67.2, 20.9, 20.6, 17.3; ESIMS: calcd
for [M+Na]+ m/z 335.1; found: m/z 335.1.
3.7. 1-O-Dodecanyl-4-O-acetyl-3-O-tert-butyldimethyl-
silyl-2-O-levulinoyl-a-L-rhamnopyranosyl-(1!4)-2,3-O-
isopropylidene-a-L-rhamnopyranoside (14)
3.5. p-Tolyl 4-O-acetyl-3-O-tert-butyldimethylsilyl-1-
thio-a-L-rhamnopyranoside (13)
To a solution of compound 12 (500.0 mg, 1.6 mmol) in
pyridine (10 mL) were added imidazole (272.3 mg,
4.0 mmol) and tert-butylchlorodimethylsilane (720.3
mg, 4.8 mmol) at 0 ꢁC. The mixture was stirred under
these conditions for 30 min and then at room tempera-
ture for another 12 h. After the reaction was complete
as judged by TLC, the reaction mixture was diluted with
cold water (50 mL) and extracted with EtOAc
(3 · 50 mL). The organic phase was dried over anhy-
drous MgSO4 and concentrated under reduced pressure.
Purification of the residue on a silica gel column (10:1,
petroleum ether–EtOAc) gave 13 (682.7 mg, 99.9%) as
To a solution of compound 4 (500.0 mg, 1.3 mmol),
compound 5 (985.7 mg, 1.9 mmol) and 4 A molecular
˚
sieves in dry CH2Cl2 (20 mL), NIS (484.5 mg,
2.1 mmol), and AgOTf (68.9 mg, 0.3 mmol) were added
at 0 ꢁC under argon. The reaction was stirred for an
additional 12 h while warming 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 (100 mL), and
washed with aqueous Na2S2O3 (50 mL), satd aq NaH-
CO3 (50 mL), brine (2 · 50 mL). The organic layer was
dried over Na2SO4, and concentrated under reduced

1164
Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
pressure. The residue was purified by silica gel column
chromatography (10:1, petroleum ether–EtOAc) to give
14 (865.4 mg, 83.4%) as a syrup: Rf 0.21 (4:1, petroleum
warming to room temperature. The mixture was diluted
with EtOAc (100 mL), washed with satd aq NaHCO3
(2 · 100 mL), brine (100 mL), dried over Na2SO4, fil-
tered, and concentrated under reduced pressure. Then,
the crude reaction mixture was purified by silica gel col-
umn chromatography (3:1, petroleum ether–EtOAc) to
give compound 16 (22.3 mg, 11.6%) as a white solid:
20
1
ether–EtOAc); ½aꢀD ꢁ41.5 (c 0.10, CHCl3); H NMR
(CDCl3) d 5.26 (d, 1H, J = 1.4 Hz, H-10), 5.14 (dd,
1H, J = 3.7, 1.8 Hz, H-20), 4.96 (t, 1H, J = 9.4 Hz, H-
40), 4.95 (s, 1H, H-1), 4.17 (dd, 1H, J = 7.3, 5.5 Hz, H-
3), 4.09 (d, J = 5.5 Hz, H-2), 3.99 (dd, 1H, J = 9.6,
3.7 Hz, H-3’), 3.76–3.71 (m, 1H, H-50), 3.70–3.65 (m,
2H, H-5 and OCHH), 3.46 (dd, 1H, J = 10.1, 7.3 Hz,
H-4), 3.43–3.39 (m, 1H, OCHH), 2.78–2.67 (m, 4H,
COCH2CH2CO), 2.20 (s, 3H, COCH3), 2.07 (s, 3H,
COCH3), 1.60–1.56 (m, 2H, bCH2), 1.53 (s, 3H, CH3),
1.33 (s, 3H, CH3), 1.31–1.28 (m, 2H, cCH2), 1.27 (d,
3H, J = 6.4 Hz, CH3-6), 1.26 (s, 16H, (CH2)8), 1.18 (d,
3H, J = 6.4 Hz, CH3-60), 0.88 (t, 3H, J = 7.1 Hz,
CH3), 0.83 (s, 9H, 3CH3), 0.07 (s, 3H, CH3), 0.05 (s,
3H, CH3); 13C NMR (CDCl3) d 206.2, 171.7, 169.8,
109.4, 96.9, 96.0, 77.9, 76.2, 73.8, 72.3, 68.3, 67.7, 67.0,
63.8, 37.9, 31.9, 30.9, 29.8–29.3, 28.1, 27.9, 26.3, 26.1,
25.4, 22.6, 21.1, 18.0, 17.8, 17.5, 14.1. ESIMS: calcd
for [M+Na]+ m/z 795.5; found: m/z 795.4.
20
Rf 0.30 (2:1, petroleum ether–EtOAc); ½aꢀD ꢁ41.5 (c
0.10, CHCl3); 1H NMR (CDCl3) d 5.09 (d, 1H,
J = 1.9 Hz, H-10), 4.99 (t, 1H, J = 9.9 Hz, H-40), 4.97
(dd, 1H, J = 3.7, 1.8 Hz, H-20), 4.95 (d, 1H,
J = 5.7 Hz, 3-OH), 4.90 (d, 1H, J = 6.4 Hz, 2-OH),
4.52 (d, 1H, J = 0.9 Hz, H-1), 4.04 (dd, 1H, J = 9.6,
3.7 Hz, H-30), 3.82–3.77 (m, 1H, H-50), 3.56 (dd, 1H,
J = 6.4, 3.2 Hz, H-2), 3.55–3.52 (m, 1H, OCHH),
3.51–3.47 (m, 1H, H-5), 3.41 (t, 1H, J = 9.6 Hz, H-4),
3.32–3.29 (m, 1H, OCHH), 2.70–2.67, 2.41–2.39 (m,
4H, COCH2CH2CO), 2.08 (s, 3H, COCH3), 2.00 (s,
3H, COCH3), 1.51–1.48 (m, 2H, bCH2), 1.24 (s, 18H,
(CH2)9), 1.16 (d, 3H, J = 5.9 Hz, CH3-6), 1.06 (d, 3H,
J = 5.9 Hz, CH3-60), 0.88 (s, 9H, C(CH3)3), 0.85 (t,
3H, J = 6.8 Hz, CH3), 0.04 (s, 3H, CH3), 0.03 (s, 3H,
CH3); 13C NMR (CDCl3) d 171.9, 109.5, 98.1, 96.8,
78.4, 77.5, 76.2, 75.1, 71.2, 70.0, 67.7, 66.2, 63.8, 31.9,
29.6–29.3, 27.9, 26.3, 26.1, 22.7, 21.1, 18.0, 17.3, 14.1.
ESIMS: calcd for [M+Na]+ m/z 755.4; found: m/z
755.3.
3.8. 1-O-Dodecanyl-4-O-acetyl-a-L-rhamnopyranosyl-
(1!4)-2,3-O-isopropylidene-a-L-rhamnopyranoside (15)
To a stirred solution of 14 (50.4 mg, 0.065 mmol) in THF
(20 mL), TBAF (65.2 lL) was added at 0 ꢁC under argon.
The reaction mixture was stirring overnight while warm-
ing to room temperature. Then, the mixture was concen-
trated and the residue was purified by silica gel column
chromatography (3:1, petroleum ether–EtOAc) to give
compound 15 (16.5 mg, 45.0%) as a syrup: Rf 0.52 (1:1,
3.10. p-Tolyl 4-O-acetyl-3-O-(p-methoxybenzyl)-1-thio-
a-L-rhamnopyranoside (17)
A mixture of 12 (500 mg, 1.6 mmol) and Bu2SnO
(700 mg, 1.8 mmol) in toluene (20 mL) was refluxed
for 6 h. Then the solution was concentrated. The residue
was suspended in DMF (25 mL), and Bu4NI (618.2 mg,
1.9 mmol) and PMBCl (258 lL, 1.9 mmol) were added.
After being stirred at room temperature for 36 h, the
mixture was diluted with CH2Cl2 (100 mL) and washed
with H2O (3 · 50 mL). The separated water phase was
extracted with CH2Cl2 (2 · 100 mL). The combined
organic phase was washed with ice water (2 · 100 mL),
dried over Na2SO4, and then filtered through a short
column of silica gel. The eluent was concentrated to a
residue, which was purified by silica gel column chroma-
tography (10:1, petroleum ether–EtOAc) to afford a
white solid 17 (513.7 mg, 74.1%): Rf 0.27 (4:1, petroleum
20
petroleum ether–EtOAc); ½aꢀD ꢁ76.4 (c 0.10, CHCl3);
1H NMR (DMSO-d6) d 5.13 (d, 1H, J = 1.9 Hz, H-10),
5.12(d, 1H, J = 4.1 Hz, 30-OH), 4.90 (s, 1H, H-1), 4.85
(d, 1H, J = 6.0 Hz, 30-OH), 4.79 (t, 1H, J = 9.7 Hz, H-
40), 4.10–4.05 (m, 2H, H-2 and H-3), 3.69 (br s, 1H, H-
20), 3.62–3.52 (m, 4H, H-30, H-50, H-5 and OCHH),
3.42–3.39 (m, 1H, OCHH), 3.35 (dd, 1H, J = 10.1,
6.8 Hz, H-4), 2.04 (s, 3H, COCH3), 1.53–1.51 (m, 2H,
bCH2), 1.43 (s, 3H, CH3), 1.28 (s, 3H, CH3), 1.24 (s,
18H, (CH2)9), 1.16 (d, 3H, J = 6.4 Hz, CH3-6), 1.04 (d,
3H, J = 6.4 Hz, CH3-60), 0.85 (t, 3H, J = 7.1 Hz, CH3);
13C NMR (CDCl3) d 171.9, 109.5, 98.1, 96.8, 78.4, 77.5,
76.2, 75.1, 71.2, 70.0, 67.7, 66.2, 63.8, 31.9, 29.6–29.3,
26.3, 26.1, 22.7, 21.1, 18.0, 17.3, 14.1. ESIMS: calcd for
[M+Na]+ m/z 583.3; found: m/z 583.3.
20
1
ether–EtOAc); ½aꢀD ꢁ157.7 (c 0.10, CHCl3); H NMR
(DMSO-d6) d 7.32 (d, 2H, J = 7.0 Hz, Ph), 7.24 (dd,
2H, J = 11.0, 2.0 Hz, Ph), 7.17 (d, 2H, J = 7.0 Hz,
Ph), 6.93 (dd, 2H, J = 11.0, 2.0 Hz, Ph), 5.50 (d, 1H,
J = 4.4 Hz, 2-OH), 5.33 (d, 1H, J = 1.3 Hz, H-1), 4.97
(t, 1H, J = 9.9 Hz, H-4), 4.55 (d, 1H, J = 11.9 Hz,
PhCHH), 4.38 (d, 1H, J = 11.9 Hz, PhCHH), 4.18
(ddd, 1H, J = 4.4, 3.2, 1.9 Hz, H-2), 4.05–4.00 (m, 1H,
H-5), 3.75 (s, 3H, OCH3), 3.54 (dd, 1H, J = 9.6,
3.2 Hz, H-3), 2.28 (s, 3H, PhCH3), 2.04 (s, 3H, COCH3),
3.9. 1-O-Dodecanyl-4-O-acetyl-3-O-tert-butyldimethyl-
silyl-2-O-levulinoyl-a-L-rhamnopyranosyl-(1!4)-a-L-
rhamnopyranoside (16)
To a stirred solution of 14 (207.8 mg, 1.2 mmol) in THF
(20 mL), HFÆpyridine (0.3 mL) was added at 0 ꢁC under
argon. The reaction mixture was stirring overnight while

Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
1165
20
1.04 (d, 3H, J = 5.8 Hz, CH3-6); 13C NMR (DMSO-d6)
d 169.7, 158.7, 137.1, 131.7, 130.1, 130.0, 129.8, 129.2,
113.6, 88.5, 75.7, 72.1, 69.4, 68.0, 67.3, 55.0, 30.6, 20.8,
20.6, 17.2. ESIMS: calcd for [M+Na]+ m/z 455.2; found:
m/z 455.1.
Rf 0.50 (2:1, petroleum ether–EtOAc); ½aꢀD ꢁ22.4 (c
0.10, CHCl3); 1H NMR (CDCl3) d 7.18 (d, 2H,
J = 8.7 Hz, Ph), 6.85 (d, 2H, J = 8.7 Hz, Ph), 5.41 (dd,
1H, J = 3.7, 1.9 Hz, H-20), 5.30 (d, 1H, J = 1.8 Hz, H-
10), 4.96 (t, 1H, J = 9.8 Hz, H-40), 4.95 (s, 1H, H-1),
4.55 (d, 1H, J = 11.5 Hz, PhCHH), 4.29 (d, 1H,
J = 11.5 Hz, PhCHH), 4.17 (dd, 1H, J = 7.3, 5.5 Hz,
H-3), 4.10 (d, 1H, J = 5.5 Hz, H-2), 3.80 (s, 3H,
OCH3), 3.77–3.74 (m, 1H, H-50), 3.71 (dd, 1H, J = 9.6,
3.2 Hz, H-30), 3.68–3.64 (m, 2H, H-5 and OCHH),
3.45 (dd, 1H, J = 9.7, 7.3 Hz, H-4), 3.44–3.40 (m, 1H,
OCHH), 2.79–2.65 (m, 4H, COCH2CH2CO), 2.15 (s,
3H, COCH3), 2.01 (s, 3H, COCH3), 1.61–1.56 (m, 2H,
bCH2), 1.54 (s, 3H, CH3), 1.34 (s, 3H, CH3), 1.27 (s,
18H, (CH2)9), 1.24 (d, 3H, J = 6.4 Hz, CH3-6), 1.18 (d,
3H, J = 6.0 Hz, CH3-60), 0.88 (t, 3H, J = 7.1 Hz,
CH3); 13C NMR (CDCl3) d 171.9, 169.9, 159.1, 130.0,
129.9, 129.4, 113.6, 109.5, 96.8, 96.1, 78.0, 76.2, 74.0,
72.2, 70.6, 68.5, 67.7, 67.0, 63.8, 55.2, 38.1, 31.9, 29.8–
29.3, 28.5, 28.1, 27.9, 26.4, 26.1, 22.7, 21.0, 17.9, 17.5,
14.1. ESIMS: calcd for [M+Na]+ m/z 801.4; found:
m/z 801.3.
3.11. p-Tolyl 3-O-(p-methoxybenzyl)-1-thio-a-L-rhamno-
pyranoside (18)
20
Rf 0.51 (1:1, petroleum ether–EtOAc); ½aꢀD ꢁ140.8 (c
0.10, CHCl3); 1H NMR (DMSO-d6) d 7.34 (d, 2H,
J = 8.3 Hz, Ph), 7.30 (d, 2H, J = 7.7 Hz, Ph), 7.16 (d,
2H, J = 8.3 Hz, Ph), 6.91 (d, 2H, J = 7.7 Hz, Ph), 5.26
(d, 1H, J = 1.4 Hz, H-1), 5.18 (d, 1H, J = 4.6 Hz, 2-
OH), 5.11 (d, 1H, J = 5.9 Hz, 4-OH), 4.59 (d, 1H,
J = 11.7 Hz, PhCHH), 4.51 (d, 1H, J = 11.7 Hz,
PhCHH), 4.07 (ddd, 1H, J = 4.6, 3.2, 1.9 Hz, H-2),
3.86–3.82 (m, 1H, H-5), 3.75 (s, 3H, OCH3), 3.44 (td,
1H, J = 9.6, 5.9 Hz, H-4), 3.36 (dd, 1H, J = 9.6,
3.2 Hz, H-3), 2.28 (s, 3H, PhCH3), 1.15 (d, 3H,
J = 6.4 Hz, CH3-6). ESIMS: calcd for [M+Na]+ m/z
413.1; found: m/z 413.1.
3.12. p-Tolyl 4-O-acetyl-3-O-(p-methoxybenzyl)-2-O-
levulinoyl-1-thio-a-L-rhamnopyranoside (6)
3.14. 1-O-Dodecanyl-4-O-acetyl-2-O-levulinoyl-a-L-
rhamnopyranosyl-(1!4)-2,3-O-isopropylidene-a-L-
rhamnopyranoside (2)
Reaction of compound 17 (5.0 g, 11.6 mmol), levulinic
acid (4.0 g, 34.7 mmol), DCC (7.14 g, 34.7 mmol), and
DMAP (141.5 mg, 1.2 mmol) in dry CH2Cl2 (100 mL)
was essentially as described for 5 gave 6 (3.5 g, 56.9%)
as a white solid: Rf 0.27 (4:1, petroleum ether–EtOAc);
To a stirred mixture of 19 (81.1 mg, 0.1 mmol) in
CH2Cl2 (5 mL) and H2O (0.33 mL), was added DDQ
(35.5 mg, 0.15 mmol) at room temperature. The reaction
was stirred for 12 h until the reaction was complete as
judged by TLC. The reaction mixture was poured into
satd aq NaHCO3 (20 mL) and extracted with CH2Cl2
(2 · 50 mL). The combined organic phase was washed
with satd aq NaHCO3 (2 · 50 mL), and brine
(2 · 50 mL), dried over Na2SO4, and concentrated.
The residue was purified by silica gel column chroma-
tography (10:1, petroleum ether–EtOAc) to give 2
(58.3 mg, 85.0%) as a syrup: Rf 0.33 (2:1, petroleum
20
1
½aꢀD ꢁ30.7 (c 0.10, CHCl3); H NMR (CDCl3) d 7.32
(d, 2H, J = 8.0 Hz, Ph), 7.21 (dd, 2H, J = 8.6, 4.6 Hz,
Ph), 7.12 (d, 2H, J = 8.0 Hz, Ph), 6.88 (dd, 2H,
J = 8.6, 4.6 Hz, Ph), 5.55 (dd, 1H, J = 3.2, 1.9 Hz, H-
2), 5.35 (d, 1H, J = 1.9 Hz, H-1), 5.02 (t, 1H,
J = 9.9 Hz, H-4), 4.56 (d, 1H, J = 11.7 Hz, PhCHH),
4.34 (d, 1H, J = 11.7 Hz, PhCHH), 4.25–4.21 (m, 1H,
H-5), 3.81 (s, 3H, OCH3), 3.75 (dd, 1H, J = 9.6,
3.2 Hz, H-3), 2.75–2.66 (m, 4H, COCH2CH2CO), 2.33
(s, 3H, PhCH3), 2.16 (s, 3H, COCH3), 2.04 (s, 3H,
COCH3), 1.19 (d, 3H, J = 6.4 Hz, CH3-6); 13C NMR
(CDCl3) d 206.3, 171.8, 169.9, 159.3, 138.0, 132.3,
129.9, 129.6, 129.5, 113.7, 86.2, 74.1, 72.5, 70.7, 70.1,
67.6, 55.2, 38.0, 29.7, 28.2, 21.0, 20.9, 17.3. ESIMS:
calcd for [M+Na]+ m/z 553.2; found: m/z 553.1.
20
1
ether–EtOAc); ½aꢀD ꢁ48.4 (c 0.10, CHCl3); H NMR
(DMSO-d6) d 5.24 (br s, 1H, 30-OH), 5.08 (d, 1H,
J = 1.9 Hz, H-10), 4.97 (dd, 1H, J = 3.7, 1.9 Hz, H-20),
4.91 (s, 1H, H-1), 4.72 (t, 1H, J = 9.7 Hz, H-40), 4.08–
4.05 (m, 2H, H-2 and H-3), 3.78 (dd, 1H, J = 9.6,
3.2 Hz, H-30), 3.68–3.63 (m, 1H, H-50), 3.60–3.55 (m,
2H, H-5 and OCHH), 3.42–3.38 (m, 1H, OCHH), 3.35
(dd, 1H, J = 10.1, 6.8 Hz, H-4), 2.72–2.70, 2.57–2.55,
2.51–2.50 (m, 4H, COCH2CH2CO), 2.12 (s, 3H,
COCH3), 2.05 (s, 3H, COCH3), 1.53–1.50 (m, 2H,
bCH2), 1.41 (s, 3H, CH3), 1.30 (s, 3H, CH3), 1.24 (s,
18H, (CH2)9), 1.18 (d, 3H, J = 6.4 Hz, CH3-6), 1.08 (d,
3H, J = 6.4 Hz, CH3-60), 0.85 (t, 3H, J = 7.1 Hz,
CH3); 13C NMR (DMSO-d6) d 206.6, 171.6, 169.9,
108.7, 96.1, 95.3, 77.3, 76.6, 75.6, 73.4, 72.1, 66.8, 66.5,
66.0, 63.3, 37.4, 31.3, 29.6, 29.0–28.7, 27.7, 27.6, 26.2,
3.13. 1-O-Dodecanyl-4-O-acetyl-3-O-(p-methoxybenzyl)-
2-O-levulinoyl-a-L-rhamnopyranosyl-(1!4)-2,3-O-iso-
propylidene-a-L-rhamnopyranoside (19)
Reaction of compound 4 (200.0 mg, 0.54 mmol), com-
pound
6 (342.0 mg, 0.64 mmol), NIS (195.2 mg,
˚
0.9 mmol), AgOTf (27.8 mg, 0.1 mmol), and 4 A mole-
cular sieves in dry CH2Cl2 (20 mL) was essentially as
described for 14 gave 19 (388.4 mg, 92.9%) as a syrup:

1166
Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
25.6, 22.1, 20.9, 17.8, 17.4, 14.0. ESIMS: calcd for
and the residue was purified by silica gel column chro-
matography (6:1, petroleum ether–EtOAc) to afford 8
(237.1 mg, 86.9%) as a white solid: Rf 0.42 (4:1, petro-
[M+Na]+ m/z 681.4; found: m/z 681.3.
20
3.15. p-Tolyl 2,4-di-O-acetyl-1-thio-a-L-rhamnopyran-
oside (7)
leum ether–EtOAc); ½aꢀD ꢁ26.4 (c 0.10, CHCl3); 1H
NMR (600 Hz, CDCl3) d 8.7 (s, 1H, NH), 6.49 (s, 1H,
H-1), 4.97–4.93 (m, 2H, H-2 and H-4), 4.30 (dd, 1H,
J = 8.7, 3.7 Hz, H-3), 3.96–3.92 (m, 1H, H-5), 2.12 (s,
3H, COCH3), 1.60 (s, 3H, CH3), 1.40 (s, 3H, CH3),
1.20 (d, 3H, J = 6.4 Hz, CH3); 13C NMR (CDCl3) d
170.0, 160.1, 110.4, 95.0, 75.4, 74.6, 73.5, 67.2, 27.5,
26.4, 21.0, 17.0. ESIMS: calcd for [M–CCl3CN+Na]+
m/z 269.1; found: m/z 269.1.
To a solution of compound 20 (5.1 g, 18.7 mmol) in dry
DMF
(50 mL),
triethylorthoacetate
(4.8 mL,
28.1 mmol) was added, followed by a catalytic amount
of CSA (868.8 mg, 3.7 mmol). The mixture was stirred
for 4 h. After complete conversion by thin-layer chro-
matography (TLC) (1:1, petroleum ether–EtOAc),
Et3N was added to neutralize the solution. Ac2O
(3.5 mL, 37.4 mmol), Et3N (8 mL, 56.1 mmol), and
DMAP (228.0 mg, 1.9 mmol) were added, and the mix-
ture was allowed to stir for 1 h at room temperature.
When TLC (2:1, petroleum ether–EtOAc) showed com-
plete conversion, MeOH (1 mL) was carefully added to
destroy excess Ac2O, and the mixture was diluted with
CH2Cl2 (200 mL). The organic layer was shaken with
1 M HCl (3 · 100 mL), followed by washing with satd
aq NaHCO3 (3 · 100 mL) and water (3 · 100 mL).
Finally the organic layer was separated, dried over
Na2SO4, and evaporated to syrup. The crude product
was purified by silica gel column chromatography (6:1,
petroleum ether–EtOAc) to give 7 (4.81 g, 71.5%) as a
3.17. p-Tolyl 4-O-acetyl-2,3-O-isopropylidene-a-L-
rhamnopyranosyl-(1!3)-2,4-di-O-acetyl-1-thio-a-L-
rhamnopyranoside (3)
To a solution of compound 8 (150.0 mg, 0.4 mmol),
˚
compound 7 (113.3 mg, 0.3 mmol) and 4 A molecular
sieves in dry CH2Cl2 (5 mL), TMSOTf (3 lL,
0.03 mmol) was added at ꢁ20 ꢁC under argon. The reac-
tion mixture was stirred under these conditions for
30 min, until TLC indicated that the reaction was com-
plete. The reaction was quenched by Et3N (two drops)
and concentrated. The residue was purified by silica
gel column chromatography (4:1, petroleum ether–
EtOAc) to give 3 (186.3 mg, 99.9%) as a syrup: Rf 0.39
20
white solid: Rf 0.34 (2:1, petroleum ether–EtOAc); ½aꢀD
20
1
ꢁ144.3 (c 0.10, CHCl3); H NMR (DMSO-d6) d 7.35
(2:1, petroleum ether–EtOAc); ½aꢀD ꢁ63.4 (c 0.10,
1
(d, 2H, J = 8.0 Hz, Ph), 7.18 (d, 2H, J = 8.0 Hz, Ph),
5.51 (d, 1H, J = 5.9 Hz, 3-OH), 5.40 (d, 1H,
J = 1.4 Hz, H-1), 5.18 (dd, 1H, J = 3.7, 1.4 Hz, H-2),
4.79 (t, 1H, J = 9.9 Hz, H-4), 4.12–4.09 (m, 1H, H-5),
3.85 (ddd, 1H, J = 9.6, 5.9, 3.7 Hz, H-3), 2.29 (s, 3H,
PhCH3), 2.08 (s, 3H, COCH3), 2.07 (s, 3H, COCH3),
1.07 (d, 3H, J = 5.9 Hz, CH3-6); 13C NMR (DMSO-
d6) d 169.9, 169.8, 137.5, 131.8, 129.9, 129.2, 85.2,
73.5, 73.2, 67.2, 66.7, 20.9, 20.8, 20.6, 17.2. ESIMS:
calcd for [M+Na]+ m/z 377.1; found: m/z 377.1.
CHCl3); H NMR (CDCl3) d 7.54 (d, 2H, J = 8.0 Hz,
Ph), 7.13 (d, 2H, J = 8.0 Hz, Ph), 5.37 (dd, 1H,
J = 3.7, 1.8 Hz, H-2), 5.32 (d, J = 1.4 Hz, H-1), 5.14
(t, 1H, J = 9.8 Hz, H-4), 5.13 (s, 1H, H-10), 4.83 (dd,
1H, J = 10.1, 8.2 Hz, H-40), 4.33–4.28 (m, 1H, H-5),
4.15 (dd, 1H, J = 9.6, 3.2 Hz, H-3), 4.09 (dd, 1H,
J = 8.2, 5.5 Hz, H-30), 4.04 (d, 1H, J = 5.5 Hz, H-20),
3.73–3.68 (m, 1H, H-50), 2.33 (s, 3H, PhCH3), 2.15,
2.13, 2.10 (s, each 3H, 3 · COCH3), 1.55 (s, 3H, CH3),
1.33 (s, 3H, CH3), 1.23 (d, 3H, J = 6.4 Hz, CH3-6),
1.16 (d, 3H, J = 6.4 Hz, CH3-60); 13C NMR (CDCl3) d
170.2, 170.0, 138.2, 132.4, 130.0, 129.4, 109.7, 99.4,
86.1, 76.0, 75.5, 74.4, 74.0, 73.3, 73.2, 67.8, 64.9, 27.6,
26.4, 21.1, 21.0, 20.9, 17.3, 16.7. ESIMS: calcd for
[M+Na]+ m/z 605.2; found: m/z 605.1.
3.16. 4-O-Acetyl-2,3-O-isopropylidene-a-L-rhamno-
pyranosyl trichloroacetimidate (8)
To a stirred solution of 11 (4.0 g, 11.3 mmol) in acetone
(72 mL) and H2O (8 mL) at ꢁ20 ꢁC was added NBS
(6.0 g, 34.1 mmol). After 5 min, the reaction was
quenched with satd aq NaHCO3 and concentrated.
The residue was diluted with CHCl3 (200 mL) and
washed with satd aq NaHCO3 (100 mL), brine
(2 · 100 mL), dried over Na2SO4, and concentrated in
vacuo. The residue was purified by silica gel column
chromatography (4:1, petroleum ether–EtOAc) to afford
a white solid (2.4 g, 84.5%): Rf 0.48, 0.23 (2:1, petroleum
ether–EtOAc). To a stirred solution of the white solid
(150 mg, 0.6 mmol) and CCl3CN (368.7 lL, 3.7 mmol)
in CH2Cl2 (10 mL) at 0ꢁC was added DBU (47 lL,
0.3 mmol). After 4 h, the solution was concentrated
3.18. 1-O-Dodecanyl-4-O-acetyl-2,3-O-isopropylidene-a-
L-rhamnopyranosyl-(1!3)-2,4-di-O-acetyl-a-L-rhamno-
pyranosyl-(1!3)-4-O-acetyl-2-O-levulinoyl-a-L-rhamno-
pyranosyl-(1!4)-2,3-O-isopropylidene-a-L-rhamno-
pyranoside (21)
Reaction of compound 2 (100.5 mg, 0.15 mmol), com-
pound
3
(266.6 mg, 0.45 mmol), NIS (57.7 mg,
˚
0.26 mmol), AgOTf (7.7 mg, 0.03 mmol), and 4 A
molecular sieves in dry CH2Cl2 (20 mL) was essentially
as described for 16 gave 21 (105.0 mg, 61.6%) as a syrup:
Rf 0.38 (2:1, petroleum ether–EtOAc); ½aꢀD ꢁ42.5 (c
20

Z. Zhang et al. / Carbohydrate Research 342 (2007) 1159–1168
1167
0.19, CHCl3); 1H NMR (CDCl3) d 5.24 (d, 1H,
J = 1.4 Hz, H-10), 5.22 (s, 1H, H-100), 5.21 (dd, 1H,
J = 3.2, 1.9 Hz, H-20), 5.05 (t, 1H, J = 9.6 Hz, H-40),
5.04 (t, 1H, J = 9.6 Hz, H-400), 4.94 (s, 1H, H-1000), 4.92
(dd, 1H, J = 3.2, 1.9 Hz, H-200), 4.84 (s, 1H, H-1), 4.79
(dd, 1H, J = 10.1, 8.3 Hz, H-4000), 4.19 (dd, 1H,
J = 10.1, 3.2 Hz, H-300), 4.16 (dd, 1H, J = 7.3, 5.5 Hz,
H-3), 4.09–4.07 (m, 2H, H-2 and H-3000), 4.02 (d, 1H,
J = 5.5 Hz, H-2000), 3.99 (dd, 1H, J = 10.1, 3.2 Hz, H-
30), 3.92–3.87 (m, 1H, H-500), 3.79–3.75 (m, 1H, H-50),
3.68–3.65 (m, 2H, H-5 and OCHH), 3.64–3.59 (m, 1H,
H-5000), 3.46 (dd, 1H, J = 9.6, 7.3 Hz, H-4), 3.43–3.39
(m, 1H, OCHH), 2.89–2.69 (m, 4H, COCH2CH2CO),
2.24 (s, 3H, COCH3), 2.14 (s, 3H, COCH3), 2.13 (s,
3H, COCH3), 2.12 (s, 3H, COCH3), 2.09 (s, 3H,
COCH3), 1.60–1.55 (m, 2H, bCH2), 1.53 (s, 3H, CH3),
1.52 (s, 3H, CH3), 1.32 (s, 3H, CH3), 1.31 (s, 3H,
CH3), 1.27 (br s, 21H, CH3-6 and (CH2)9), 1.19 (d,
6H, J = 5.9 Hz, CH3-60 and CH3-600), 1.10 (d, 3H,
J = 6.4 Hz, CH3-6000), 0.88 (t, 3H, J = 7.1 Hz, CH3);
13C NMR (CDCl3) d 206.1, 171.7, 170.4, 170.3, 170.2,
170.1, 109.6, 109.5, 99.4, 99.2, 96.8, 95.8, 77.9, 77.5,
76.2, 76.0, 75.6, 74.7, 74.2, 74.1, 72.6, 72.4, 72.2, 71.5,
67.8, 67.3, 67.2, 64.6, 63.7, 37.8, 31.9, 29.8–29.3, 28.3,
27.9, 27.6, 26.4, 26.1, 23.8, 22.7, 21.1, 20.9, 20.7, 18.0,
17.4, 17.3, 16.5, 14.1. ESIMS: calcd for [M+Na]+ m/z
1139.6; found: m/z 1139.5.
J = 6.4 Hz, CH3-600), 1.06 (d, 3H, J = 6.4 Hz, CH3-60),
1.01 (d, 3H, J = 6.0 Hz, CH3-6000), 0.85 (t, 3H,
J = 6.9 Hz, CH3); 13C NMR (DMSO-d6) d 170.4,
170.3, 170.2, 170.1, 163.4, 109.3, 109.0, 99.2, 99.1,
98.6, 96.4, 78.0, 77.8, 75.8, 75.7, 74.8, 74.1, 73.9, 72.5,
72.0, 71.7, 70.2, 67.1, 66.9, 66.4, 64.3, 63.6, 31.5, 30.9,
29.2–28.9, 27.9, 27.7, 26.4, 26.3, 25.8, 22.4, 20.9, 20.8,
20.7, 20.7, 18.1, 17.5, 17.3, 16.4, 14.2. ESIMS: calcd
for [M+Na]+ m/z 1041.5; found: m/z 1041.6.
3.20. 1-O-Dodecanyl-4-O-acetyl-a-L-rhamnopyranosyl-
(1!3)-2,4-di-O-acetyl-a-L-rhamnopyranosyl-(1!3)-4-O-
acetyl-a-L-rhamnopyranosyl-(1!4)-a-L-rhamnopyran-
oside (1)
Compound 22 (53.4 mg, 0.05 mmol) was dissolved in
80% HOAc (7.5 mL) and stirred for 2 h at 80 ꢁC, then
the reaction mixture was concentrated. The residue
was purified by silica gel column chromatography
(30:1-10:1, CHCl3–MeOH) to give compound
1
20
(40.7 mg, 82.7%) as a gummy solid: ½aꢀD ꢁ63.9 (c 0.40,
20
MeOH), (Ref. 10 ½aꢀD ꢁ59.5 (c 0.40, MeOH)); Rf 0.32
1
(8:1, CHCl3–CH3OH); H NMR (CD3OD) d 5.22 (d,
1H, J = 1.4 Hz, H-10), 5.11 (t, 1H, J = 9.8 Hz, H-40),
5.04 (dd, 1H, J = 3.2, 1.4 Hz, H-200), 4.97 (t, 1H,
J = 10.1 Hz, H-400), 4.89 (tobsc, 1H), 4.87 (d, 1H,
J = 1.4 Hz, H-100), 4.82 (d, 1H, J = 1.3 Hz, H-1000), 4.63
(d, 1H, J = 1.3 Hz, H-1), 4.25 (dd, 1H, J = 10.1,
3.7 Hz, H-300), 4.05 (br d, 1H, J = 3.2 Hz, H-20), 4.08–
4.03 (m, 1H, H-500), 3.90–3.86 (m, 1H, H-50), 3.87 (dd,
1H, J = 10.1, 3.2 Hz, H-30), 3.74–3.72 (m, 2H, H-2
and H-3), 3.70 (dd, 1H, J = 3.2, 1.9 Hz, H-2000), 3.66
(dd, 1H, J = 7.3, 3.2 Hz, H-3000), 3.67–3.60 (m, 3H,
OCHH, H-5000 and H-5), 3.51 (t, 1H, J = 9.2 Hz, H-4),
3.40–3.37 (m, 1H, OCHH), 2.13 (s, 3H, CH3CO-40),
2.12 (s, 3H, CH3CO-200), 2.08 (s, 3H, CH3CO-400), 2.10
(s, 3H, CH3CO-4000), 1.62–1.53 (m, 2H, bCH2), 1.37–
1.34 (m, 2H, cCH2), 1.29 (br s, 16H, (CH2)8), 1.26 (d,
3H, J = 6.4 Hz, CH3-6), 1.16 (d, 3H, J = 6.4 Hz, CH3-
600), 1.14 (d, 3H, J = 6.4 Hz, CH3-60), 1.09 (d, 3H,
J = 6.4 Hz, CH3-6000), 0.88 (t, 3H, J = 7.1 Hz, CH3);
13C NMR (6:1, C5D5N–CD3OD) d 171.6, 171.0, 170.5,
103.9, 103.5, 101.7, 100.6, 81.1, 80.5, 75.4, 75.3, 73.6,
73.4, 73.1, 73.0, 72.5, 71.9, 70.2, 68.4, 68.3, 68.1, 68.0,
67.6, 32.5, 30.3–30.0, 26.9, 23.3, 21.3, 21.2, 21.0, 20.9,
19.3, 18.1, 17.8, 14.6. HRESIMS: calcd for
C44H74O21Na+ 961.4620; found, 961.4626, (Ref. 12
961.4739).
3.19. 1-O-Dodecanyl-4-O-acetyl-2,3-O-isopropylidene-a-
L-rhamnopyranosyl-(1!3)-2,4-di-O-acetyl-a-L-rhamno-
pyranosyl-(1!3)-4-O-acetyl-a-L-rhamnopyranosyl-
(1!4)-2,3-O-isopropylidene-a-L-rhamnopyranoside (22)
To a stirred solution of 21 (77.0 mg, 0.07 mmol) in
CH2Cl2 (5 mL) and CH3OH (5 mL) was added
NH2NH2ÆHOAc (63.5 mg, 0.70 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 22 (57.6 mg, 82.1%) as a syrup:
20
Rf 0.38 (2:1, petroleum ether–EtOAc); ½aꢀD ꢁ44.8 (c
0.10, CHCl3); 1H NMR (DMSO-d6) d 5.46 (d, 1H,
J = 4.6 Hz, 20-OH), 5.15 (s, 1H, H-10), 5.03 (s, 1H, H-
100), 4.96 (t, 1H, J = 9.9 Hz, H-40), 4.91 (s, 1H, H-1000),
4.89 (d, 1H, J = 3.2 Hz, H-200), 4.84 (t, 1H,
J = 10.1 Hz, H-400), 4.80 (s, 1H, H-1), 4.64 (dd, 1H,
J = 9.7, 8.3 Hz, H-4000), 4.18 (dd, 1H, J = 10.1, 3.2 Hz,
H-300), 4.11–4.04 (m, 4H, H-2, H-3, H-500, and H-3000),
3.98 (d, 1H, J = 5.0 Hz, H-2000), 3.78 (br s, 1H, H-20),
3.71 (dd, 1H, J = 10.1, 2.7 Hz, H-30), 3.68–3.64 (m,
1H, H-50), 3.60–3.53 (m, 3H, H-5, H-5000 and OCH2),
3.42–3.39 (m, 1H, OCH2), 3.36 (tobsc, 1H, H-4), 2.10
(s, 3H, COCH3), 2.08 (s, 3H, COCH3), 2.07 (s, 3H,
COCH3), 2.05 (s, 3H, COCH3), 1.53–1.51 (m, 2H,
bCH2), 1.43 (s, 3H, CH3), 1.41 (s, 3H, CH3), 1.28 (s,
3H, CH3), 1.25 (s, 3H, CH3), 1.24 (br s, 18H, (CH2)9),
1.18 (d, 3H, J = 6.4 Hz, CH3-6), 1.08 (d, 3H,
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