Synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera

Article abstract of DOI:10.1002/hlca.201300195

Chemical synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the bark of Albizia procera has been accomplished through a concise stepwise glycosylation strategy starting from commercially available D-xylose, 2-acetamido-2-deoxy-D-glucose and L-arabinose. The target trisaccharide was designed with a 4-methoxyphenyl (MP) aglycone to extend the scope of conversion to suitable glycoconjugates via selective removal of 4-methoxyphenyl (MP) group. An unexpected phenomenon, i.e., the arabinosyl residue assumed the ¹C₄ conformation instead of the typical ⁴C₁ form, was observed. Deprotection could restore the normal conformation. Copyright

Full text of DOI:10.1002/hlca.201300195

Helvetica Chimica Acta – Vol. 97 (2014)
361
Synthesis of a Trisaccharide Related to the Cytotoxic Triterpenoid Saponins
Isolated from the Bark of Albizia procera
by Qing-Chao Liu*a), Tian-Tian Guob), Cong Zhaoa), Jing Suna), and Wen-Hong Li*a)
a) Department of Pharmaceutical Engineering, Northwest University, Xiꢀan 710069, P. R. China
(fax: þ 86-29-88305682; e-mail: liuqc21@nwu.edu.cn)
b) Department of Chemical Medicine, Xiꢀan Institute for Food and Drug Control, Xiꢀan 710054,
P. R. China
Chemical synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins isolated from the
bark of Albizia procera has been accomplished through a concise stepwise glycosylation strategy starting
from commercially available d-xylose, 2-acetamido-2-deoxy-d-glucose and l-arabinose. The target
trisaccharide was designed with a 4-methoxyphenyl (MP) aglycone to extend the scope of conversion to
suitable glycoconjugates via selective removal of 4-methoxyphenyl (MP) group. An unexpected
phenomenon, i.e., the arabinosyl residue assumed the 1C4 conformation instead of the typical 4C1 form,
was observed. Deprotection could restore the normal conformation.
Introduction. – Triterpenoid saponins, which are widely distributed in terrestrial
plants and in some marine organisms, have been reported to present a broad spectrum
of well-defined biological and physiological features such as anti-HIV, antitumor, and
anti-inflammatory activities [1 – 11]. One of the common features of triterpenoid
saponins is the presence of a 3-O-sugar residue [12 – 14]. It was reported that the
naturally occurring triterpenoid saponins containing N-acetylglucosamine are rare;
however, most of these exhibit important antiproliferative activities [15 – 17]. It is well-
known that the glycosylation step usually occurs in the mature stage of triterpenoid
saponins, yet the biosynthetic pathways for the formation of glycosides are nearly
almost unknown. Therefore, chemical synthesis of triterpenoid saponins is needed to
rationalize the biosynthetic pathway and to gain access to adequate amounts of
triterpenoid saponins for promoting further pharmaceutical studies.
The bark of the plant Albizia procera is widely used as folk medicine in Egypt for
the treatment of pregnancy and stomachache. Recently, Melek et al. reported the
chemical structures of three new triterpenoid saponins containing N-acetylglucos-
amine, i.e., proceraosides A, B, and D, isolated from the bark of Albizia procera which
showed important in vitro cytotoxic activity against HEPG2 cell line. Here, we report
the efficient synthesis of a trisaccharide related to the cytotoxic triterpenoid saponins
isolated from the bark of Albizia procera as a 4-methoxyphenyl (MP) glycosides
(Scheme 1) [18].
Results and Discussion. – For the synthesis of the target trisaccharide 1, a stepwise
glycosylation strategy was adopted involving the syntheses of suitably protected d-
xylose, 2-acetamido-2-deoxy-d-glucose, and l-arabinose synthons. The choice of the 4-
ꢁ 2014 Verlag Helvetica Chimica Acta AG, Zꢂrich

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Helvetica Chimica Acta – Vol. 97 (2014)
Scheme 1. Structures of the Triterpenoid Saponins and the Target Trisaccharide 1
methoxyphenyl (MP) group at the reducing end was favored by the fact that it can be
converted to suitable glycoconjugates through the ammonium ceric nitrate (CAN)-
mediated oxidative cleavage [19].
As outlined in Scheme 2, 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-d-glucopyra-
nose (2) was reacted with 4-methoxyphenol in the presence of BF3 · Et2O to afford the
required 4-methoxyphenyl glycoside, i.e., 4-methoxyphenyl 2-acetamido-3,4,6-tri-O-
Ac-2-deoxy-b-d-glucopyranoside (3) in 86% yield [20]. Subsequently, the O-Ac groups
were selectively removed using MeONa in MeOH, furnishing the corresponding 4-
methoxyphenyl 2-acetamido-2-deoxy-b-d-glucopyranoside (4) in 90% yield [21].
t
Seletive protection of the primary OH group with a BuPh2Si (TBDPS) group
t
employing BuPh2SiCl in pyridine, followed by benzoyl (Bz) protection of the other
OH groups using BzCl afforded the completely protected compound 5, 2-acetamido-
3,4-di-O-benzoyl-6-O-[(tert-butyl)(diphenyl)silyl]-2-deoxy-b-d-glucopyranoside,
in
83% yield over two steps [22]. Removal of the TBDPS group using Bu4NF in THF
gave the desired acceptor 6, 2-acetamido-3,4-di-O-benzoyl-2-deoxy-b-d-glucopyrano-
side, in 87% yield [23]. For the l-arabinose moiety, the known 1-thio-a-l-arabinopyr-
anoside 7 was converted to its 3,4-isopropylidene derivative 8 in 96% yield using 2,2-
dimethoxypropane in the presence of camphor-10-sulfonic acid (CSA) [24]. Finally, the
l-arabinosyl donor 9 was obtained by protecting the 2-OH group of 8 as an acetate in
91% yield.
With the completion of the synthesis of acceptor 6 and donor 9, we next turned our
attention to a stepwise strategy for the efficient synthesis of the target trisaccharide 1.
Glycosylation between acceptor 6 and donor 9 was accomplished via thioglycoside
activation with N-iodosuccinimide (NIS) in the presence of silver trifluoromethane-
sulfonate (TfOAg) to afford the disaccharide 10 in 86% yield. Subsequently, the Ac
group at the O-atom of the disaccharide 10 was selectively removed using 1% AcCl in
MeOH, furnishing the required disaccharide acceptor 11 in 90% yield [25]. Further

Helvetica Chimica Acta – Vol. 97 (2014)
363
Scheme 2.
t
a) 4-Methoxyphenol, BF3 · Et2O, CH2Cl2, ꢀ 308; 87%. b) MeONa, MeOH, r.t.; 97%. c) BuPh2SiCl
(TBDPSCl), Py; PhCOCl (BzCl); 82% for two steps. d) Bu4NF, THF, r.t.; 83%. e) 2,2-Dimethoxy-
propane, camphor-10-sulfonic acid (CSA), DMF; 96%. f) Ac2O, 4-(Dimethylamino)pyridine
(DMAP), Et3N, CH2Cl2; 91%. g) N-Iodosuccinimide (NIS), TfOAg, CH2Cl2, 4-ꢃ molecular sieves,
08; 86%. h) 1% AcCl in MeOH, CH2Cl2, r.t.; 90%. i) 12, Trimethylsilyl trifluoromethanesulfonate
(TMSOTf), CH2Cl2, 4-ꢃ molecular sieves, ꢀ 308; 87%. j) TsOH, CH2Cl2, MeOH; 89%. k) MeONa,
CH2Cl2, MeOH; 80%.

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glycosylation of the known donor, 2,3,4-tri-O-benzoyl-b-d-xylopyranosyl trichloroace-
timidate (12) [26] with disaccharide acceptor 11 employing trimethylsilyl trifluorome-
thanesulfonate (TMSOTf) as promoter afforded the protected trisaccharide 13 in 87%
yield. Deprotection of the isopropylidene ketal with TsOH in CH2Cl2 and MeOH gave
the trisaccharide 14 in 89% yield [26][27]. However, it was found that the signal of
HꢀC(1) of the arabinosyl residue of 14 was a broad singlet, which is also characterized
3
3
by a large J(3’,OH) value of 9.1 Hz and a large J(4’,OH) value of 8.3 Hz in CDCl3
1
(Fig.). These results indicated that the arabinosyl residue adopted the C4 conforma-
4
1
tion instead of the typical C1 form. We presumed that the C4 conformation of
compound 14 could be ascribed to cooperative O(4’)ꢀH · O(3’)ꢀH · O(1’) H-bonds
[28][29]. This phenomenon was consistent with that reported in the literature [30].
Hence, the structure of 14 should be 14’. Finally, removal of Bz groups using MeONa in
MeOH furnished the target trisaccharide in 80% yield. Interestingly, the arabinopyr-
anosyl moiety returned to the normal 4C1 conformation, and this was supported by the
3
HꢀC(1) signal of arabinopyranosyl moiety of 1 (J(1’,2’) ¼ 5.7), and a large J(3’,OH)
3
value of 9.1 Hz and a large J(4’,OH) value of 8.3 Hz in CDCl3.
Figure. J(H,OH) and d (OH) values of the intermediate 14’ in CDCl3. ---: Intramolecular H-bonds
Conclusions. – In summary, we have synthesized a trisaccharide related to the
cytotoxic triterpenoid saponins isolated from the bark of Albizia procera. A concise
stepwise glycosylation strategy was developed for the construction of the trisaccharide
with a 4-methoxyphenyl aglycone which could extend the scope of conversions to
suitable glycoconjugates via selective removal of 4-methoxyphenyl group. Interest-
1
ingly, the arabinopyranosyl residue in 14’ adopted a C4 conformation instead of the
4
typical C1 form, and deprotection of acyl groups led to the normal conformation.
This work was financially supported by the Doctoral Program Foundation of Institutions of Higher
Education of China (No. 20116101120025), the China Postdoctoral Science Foundation (Nos.
2012M512023 and 2013T60887), the Postdoctoral Science Foundation of Northwest University
(BSH11012), the Foundation of Shaanxi Educational Committee (11JK0676), and the Scientific
Research Foundation of Northwest University (NG10003).
Experimental Part
General. Commercial reagents were used without further purification unless specified. Solvents were
dried and redistilled prior to use in the usual way. TLC: Precoated silica gel 60 F254 plates (SiO2; E.
Merck). Flash column chromatography (CC): SiO2 (200 – 300 mesh). Optical rotations: PerkinElmer

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365
241MC polarimeter. 1H- and 13C-NMR spectra: Jeol-JNM-ECP-600 spectrometer; d in ppm rel. to Me4Si
as internal standard, J in Hz. MS: Q-TOF-Global mass spectrometer; in m/z.
4-Methoxyphenyl 3,4,6-Tri-O-acetyl-2-(acetylamino)-2-deoxy-b-d-glucopyranoside (3). Compound 2
(3.00 g, 7.70 mmol) and 4-methoxyphenol (783 mg, 6.42 mmol) were dissolved in dry CH2Cl2 (35 ml).
BF3 · Et2O (1.20 ml, 9.63 mmol) was added at ꢀ 308. The mixture was allowed to warm to r.t. and stirred
for 7 h. Then, the mixture was washed with sat. NaHCO3 (3 ꢁ 20 ml) and NaCl (3 ꢁ 20 ml). The org. layer
was dried (Na2SO4) and concentrated. The residue was purified by CC on SiO2 (petroleum ether/AcOEt
3 :1) to afford 3 (2.91 g, 87%). White solid. [a]2D7 ¼ ꢀ13.1 (c ¼ 1.2, CHCl3). 1H-NMR (CDCl3, 600 MHz):
7.96 (d, J ¼ 7.5, NH); 6.93 (d, J ¼ 9.1, 2 arom. H); 6.76 (d, J ¼ 9.1, 2 arom. H); 5.95 (d, J ¼ 7.9, HꢀC(1));
5.39 (t, J ¼ 9.6, HꢀC(3)); 5.16 (t, J ¼ 9.6, HꢀC(4)); 4.29 (dd, J ¼ 12.1, 5.5, HaꢀC(6)); 4.15 (ddd, J ¼ 9.6, 7.9,
7.5, HꢀC(2)); 4.07 (dd, J ¼ 12.1, 2.4, HbꢀC(6)); 3.84 – 3.81 (m, HꢀC(5)); 3.76 (s, MeO); 2.08, 2.06, 2.04,
1.96 (4s, 4 Me). HR-ESI-MS: 476.1546 ([M þ Naþ], C21H27NNaO1þ0 ; calc. 476.1527).
4-Methoxyphenyl 2-(Acetylamino)-2-deoxy-b-d-glucopyranoside (4). Compound
3 (2.50 g,
5.52 mmol) was dissovled in dry MeOH (50 ml), and a cat. amount of MeONa was added. After
stirring for 30 min, the mixture was neutralized with resin (Hþ); and the resin was filtered. The solvent
was concentrated, and the residue was purified by CC (SiO2; CHCl3/MeOH 10 :1) to afford 4 (1.75 g,
97%). White solid. [a]2D7 ¼ ꢀ9.8 (c ¼ 1.1, MeOH). 1H-NMR (CD3OD, 600 MHz): 6.91 (d, J ¼ 9.3, 2 arom.
H); 6.79 (d, J ¼ 9.3, 2 arom. H); 5.16 (d, J ¼ 7.8, HꢀC(1)); 4.87 (t, J ¼ 9.6, HꢀC(3)); 4.35 (t, J ¼ 9.6,
HꢀC(4)); 3.97 (dd, J ¼ 12.3, 5.3, HaꢀC(6)); 3.68 (dd, J ¼ 9.6, 7.8, HꢀC(2)); 3.65 (s, MeO); 3.41 (dd, J ¼
12.4, 2.3, HbꢀC(6)); 3.34 – 3.30 (m, HꢀC(5)); 1.82 (s, Me). HR-ESI-MS: 328.1369 ([M þ Hþ],
C15H22NOþ7 ; calc. 328.1391).
4-Methoxyphenyl 2-(Acetylamino)-3,4-di-O-benzoyl-6-O-[(tert-butyl)(diphenyl)silyl]-2-deoxy-b-d-
t
glucopyranoside (5). To a soln. of 4 (1.50 g, 4.59 mmol) in dry pyridine (20 ml) was added BuPh2SiCl
(1.42 ml, 5.50 mmol), and the mixture was stirred at r.t. for 6 h. When TLC showed complete conversion
of the starting material, BzCl (1.10 ml, 6.89 mmol) was added, and stirring was continued for 5 h. After
complete conversion (TLC), the solvent was evaporated, and the residue was purified by CC (SiO2;
petroleum ether/AcOEt 6 :1) to afford 5 (2.91 g, 82%). White solid. [a]2D7 ¼ ꢀ15.7 (c ¼ 1.3, CHCl3).
1H-NMR (CDCl3, 600 MHz): 8.15 – 7.16 (m, 24 arom. H); 5.98 (d, J ¼ 7.8, HꢀC(1)); 5.89 (d, J ¼ 6.3, NH);
5.55 (t, J ¼ 9.6, HꢀC(3)); 4.87 (t, J ¼ 9.6, HꢀC(4)); 4.33 (dd, J ¼ 12.0, 5.6, HaꢀC(6)); 3.95 (ddd, J ¼ 9.6, 7.8,
6.3, HꢀC(2)); 3.78 (s, MeO); 3.56 (dd, J ¼ 12.0, 2.7, HbꢀC(6)); 3.39 – 3.27 (m, HꢀC(5)); 1.84 (s,
t
NHCOMe); 1.03 (s, Bu). 13C-NMR (CDCl3, 150 MHz): 171.2; 166.4; 166.2; 155.6; 151.0; 135.7; 135.6;
135.5; 133.1; 132.9; 132.7; 129.9; 129.8; 129.7; 128.3; 127.6; 127.5; 118.6; 114.4; 105.3 (C(1)); 79.6 (C(5));
72.3 (C(3)); 69.9 (C(4)); 63.7 (C(6)); 55.8 (MeO); 55.3 (C(2)); 31.2 (Me3C); 26.7 (Me3C); 22.5
(MeCONH). HR-ESI-MS: 796.2936 ([M þ Naþ], C45H47NNaO9Siþ; calc. 796.2911).
4-Methoxyphenyl 2-(Acetylamino)-3,4-di-O-benzoyl-2-deoxy-b-d-glucopyranoside (6). To a soln. of
5 (2.00 g, 2.59 mmol) in dry THF (10 ml) was added Bu4NF (1.22g, 3.89 mmol), and the soln. was stirred
at r.t. for 2 h. When TLC showed complete conversion of the starting material, the solvent was
evaporated under reduced pressure. The residue was purified by CC (SiO2; petroleum ether/AcOEt 4 :1)
to afford 6 (1.15 g, 83%). White solid. [a]2D7 ¼ ꢀ12.3 (c ¼ 1.1, CHCl3). 1H-NMR (CDCl3, 600 MHz):
8.10 – 7.41 (m, 14 arom. H); 5.87 (d, J ¼ 8.0, HꢀC(1)); 5.78 (d, J ¼ 5.9, NH); 5.65 (t, J ¼ 9.6, HꢀC(3)); 4.83
(t, J ¼ 9.6, HꢀC(4)); 4.41 (dd, J ¼ 12.1, 5.0, HaꢀC(6)); 3.89 (ddd, J ¼ 9.6, 8.0, 5.9, HꢀC(2)); 3.67 (s, MeO);
3.57 – 3.64 (m, HꢀC(5), HbꢀC(6)); 1.82 (s, NHCOMe). 13C-NMR (CDCl3, 150 MHz): 169.9; 166.3; 166.0;
153.7; 150.3; 135.7; 133.1; 132.7; 129.9; 129.7; 128.3; 127.9; 127.3; 118.4; 115.0; 105.0 (C(1)); 79.4 (C(5));
72.6 (C(3)); 69.7 (C(4)); 63.2 (C(6)); 55.6 (MeO); 55.4 (C(2)); 22.5 (MeCONH). HR-ESI-MS: 558.1717
([M þ Naþ], C29H29NNaOþ9 ; calc. 558.1733).
4-Methylphenyl 3,4-O-(1-Methylethylidene)-1-thio-a-l-arabinopyranoside (8). To a soln. of
7
(2.00 g, 7.81 mmol) in DMF (10 ml) was added 2,2-dimethoxypropane (1.94 ml, 15.6 mmol) and
camphor-10-sulfonic acid (CSA; 0.61 g, 2.56 mmol) at 508 under vacuum. After 5 h, the reaction soln. was
diluted with AcOEt (80 ml) and then washed with sat. aq. NaHCO3 and brine, and dried (Na2SO4). The
solvent was removed, and the residue was purified by CC (SiO2; petroleum ether/AcOEt 7:1) to afford 8
(2.22 g, 96%). White solid. [a]2D7 ¼ þ23.1 (c ¼ 1.6, CHCl3). 1H-NMR (CDCl3, 600 MHz): 7.45 (d, J ¼ 8.3, 2
arom. H); 7.11 (d, J ¼ 8.3, 2 arom. H); 4.46 (d, J ¼ 7.8, HꢀC(1)); 4.29 – 4.26 (m, HꢀC(4)); 4.23 (dd, J ¼ 8.1,
4.0, HꢀC(3)); 4.08 (dd, J ¼ 12.7, 5.7, HaꢀC(5)); 3.76 (dd, J ¼ 13.2, 3.6, HbꢀC(5)); 3.63 – 3.60 (m, HꢀC(2));

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2.33 (s, 3 H); 1.46 (s, 3 H); 1.33 (s, 3 H). 13C-NMR (CDCl3, 150 MHz): 138.5; 133.2; 129.7; 128.1; 110.0
(Me2C); 88.6 (C(1)); 77.9 (C(3)); 72.9 (C(4)); 71.3 (C(2)); 65.8 (C(5)); 27.8 (Me2C); 26.1 (Me2C); 21.0
(Me of TolS). HR-ESI-MS: 319.0994 ([M þ Naþ], C15H20NaO4Sþ; calc. 319.0975).
4-Methylphenyl 2-O-Acetyl-3,4-O-(1-methylethylidene)-1-thio-a-l-arabinopyranoside (9). To a soln.
of 8 (1.50 g, 4.89 mmol) in CH2Cl2 (10 ml) were added Et3N (1.06 ml, 7.52 mmol), Ac2O (0.57 ml,
6.02 mmol), and 4-(dimethylamino)pyridine (DMAP; 13 mg, 0.10 mmol). The soln. was stirred at r.t. for
1.5 h, and then diluted with CH2Cl2 (100 ml) and washed with sat. NaHCO3 and brine, and dried
(Na2SO4). The solvent was removed, and the product was purified by CC (SiO2; petroleum ether/AcOEt
8 :1) to afford 9 (1.50 g, 91%). White solid. [a]2D7 ¼ þ26.9 (c ¼ 1.8, CHCl3). 1H-NMR (CDCl3, 600 MHz):
7.40 (d, J ¼ 8.0, 2 arom. H); 7.12 (d, J ¼ 8.0, 2 arom. H); 5.14 (t, J ¼ 7.2, HꢀC(2)); 4.77 (d, J ¼ 7.2, HꢀC(1));
4.30 (dd, J ¼ 7.2, 3.7, HꢀC(3)); 4.25 – 4.21 (m, HꢀC(4)); 4.17 (dd, J ¼ 12.6, 5.3, HaꢀC(5)); 3.77 (dd, J ¼
12.6, 3.6, HbꢀC(5)); 2.34 (s, 3 H); 2.13 (s, 3 H); 1.57 (s, 3 H); 1.36 (s, 3 H). 13C-NMR (CDCl3,
150 MHz): 170.3 (MeCO); 139.6; 133.2; 129.7; 128.3; 110.7 (Me2C); 88.3 (C(1)); 77.9 (C(3)); 73.1 (C(4));
71.6 (C(2)); 65.9 (C(5)); 28.1 (Me2C); 26.3 (Me2C); 21.3 (Me of TolS); 21.0 (MeCO). HR-ESI-MS:
361.1113 ([M þ Naþ], C17H22NaO5Sþ; calc. 361.1081).
4-Methoxyphenyl 2-(Acetylamino)-6-O-[2-O-acetyl-3,4-O-(1-methylethylidene)-a-l-arabinopyrano-
syl]-3,4-di-O-benzoyl-2-deoxy-b-d-glucopyranoside (10). A mixture of 6 (500 mg, 0.93 mmol), 9
(380 mg, 1.12 mmol), and 4-ꢃ molecular sieves in dry CH2Cl2 (15 ml) was stirred at r.t. under Ar for
30 min and then cooled to 08. N-Iodosuccinimide (NIS; 420 mg, 1.86 mmol) was added, followed by silver
trifluoromethanesulfonate (TfOAg; 12 mg, 0.05 mmol), and the mixture was allowed to stir at 08 for 1 h,
until TLC showed complete disappearance of 6. The mixture was diluted with CH2Cl2 and filtered
through Celite. The filtrate was successively washed with Na2S2O3, NaHCO3, and brine. The org. layer
was collected, dried (Na2SO4), and evaporated. The residue was purified by CC (SiO2; petroleum ether/
AcOEt 4 :1) to afford 10 (599 mg, 86%). White solid. [a]2D7 ¼ þ13.8 (c ¼ 1.0, CHCl3). 1H-NMR (CDCl3,
600 MHz): 8.01 – 7.49 (m, 14 arom. H); 5.89 (d, J ¼ 7.9, HꢀC(1)); 5.71 (t, J ¼ 9.7, HꢀC(3)); 5.55 (d, J ¼ 5.9,
NH); 5.16 (dd, J ¼ 7.8, 6.8, HꢀC(2’)); 4.97 (t, J ¼ 9.7, HꢀC(4)); 4.65 (d, J ¼ 7.8, HꢀC(1’)); 4.41 (dd, J ¼ 6.8,
5.8, HꢀC(3’)); 4.33 – 4.28 (m, HꢀC(4’), HaꢀC(6)); 4.21 (dd, J ¼ 12.1, 5.1, HaꢀC(5’)); 4.06 (ddd, J ¼ 9.7, 7.9,
5.9, HꢀC(2)); 3.77 – 3.69 (m, HbꢀC(5’), HꢀC(5), HbꢀC(6)); 3.63 (s, MeO); 2.15 (s, COMe); 1.83 (s,
NHCOMe); 1.37, 1.56 (2s, 2 Me). 13C-NMR (CDCl3, 150 MHz): 171.4 (MeCO); 169.8 (MeCONH);
166.7; 166.5; 153.6; 150.2; 136.3; 133.3; 132.7; 129.8; 129.7; 128.5; 127.9; 127.3; 119.3; 115.2; 110.9 (Me2C);
109.5 (C(1’)); 105.0 (C(1)); 79.4 (C(5)); 78.3 (C(4’)); 77.6 (C(3)); 73.1 (C(2’)); 72.6 (C(4)); 71.5 (C(3’));
69.7 (C(6)); 67.0 (C(5’)); 55.6 (MeO); 55.5 (C(2)); 28.3 (Me2C); 26.5 (Me2C); 21.3 (MeCONH); 21.0
(MeCO). HR-ESI-MS: 772.2596 ([M þ Naþ], C39H43NNaO1þ4 ; calc. 772.2574).
4-Methoxyphenyl 2-(Acetylamino)-3,4-di-O-benzoyl-2-deoxy-6-O-[3,4-O-(1-methylethylidene)-a-l-
arabinopyranosyl]-b-d-glucopyranoside (11). To a soln. of 10 (500 mg, 0.67 mmol) in CH2Cl2 (8 ml) was
added a soln. of 1% AcCl in MeOH (10 ml). The mixture was stirred overnight at r.t., and TLC
(petroleum ether/AcOEt 4 :1) indicated that the reaction was complete. The mixture was concentrated in
vacuo. The residue was purified by CC (SiO2; petroleum ether/AcOEt 3.5 :1) to afford 11 (426 mg, 90%).
White solid. [a]2D7 ¼ þ15.1 (c ¼ 1.1, CHCl3). H-NMR (CDCl3, 600 MHz): 8.02 – 7.51 (m, 14 arom. H);
1
5.91 (d, J ¼ 7.7, HꢀC(1)); 5.69 (t, J ¼ 9.3, HꢀC(3)); 5.61 (d, J ¼ 6.3, NH); 5.00 (t, J ¼ 9.3, HꢀC(4)); 4.53 (d,
J ¼ 7.9, HꢀC(1’)); 4.39 (dd, J ¼ 8.6, 7.8, HꢀC(2’)); 4.37 – 4.27 (m, HꢀC(3’), HꢀC(4’), HaꢀC(6)); 4.17 (dd,
J ¼ 11.9, 5.3, HaꢀC(5’)); 4.03 (ddd, J ¼ 9.3, 7.7, 6.3, HꢀC(2)); 3.77 – 3.71 (m, HꢀC(5), HbꢀC(6)); 3.69 (dd,
J ¼ 11.9, 3.6, HbꢀC(5’)); 3.65 (s, MeO); 1.81 (s, NHCOMe); 1.35, 1.57 (2s, 2 Me). 13C-NMR (CDCl3,
150 MHz): 169.9 (MeCONH); 166.7; 166.3; 153.4; 150.2; 136.5; 133.3; 132.9; 129.7; 129.5; 128.6; 127.7;
126.9; 119.0; 115.2; 110.1 (Me2C); 108.3 (C(1’)); 105.2 (C(1)); 79.8 (C(5)); 77.9 (C(4’)); 77.6 (C(3)); 73.3
(C(2’)); 72.9 (C(4)); 71.5 (C(3’)); 69.9 (C(6)); 67.0 (C(5’)); 55.6 (MeO); 55.4 (C(2)); 28.3 (Me2C); 26.5
(Me2C); 21.3 (MeCONH). HR-ESI-MS: 730.2497 ([M þ Naþ], C37H41NNaO1þ3 ; calc. 730.2473).
4-Methoxyphenyl 2,3,4-Tri-O-benzoyl-b-d-xylopyranosyl-(1 ! 2)-3,4-O-(1-methylethylidene)-a-l-
arabinopyranosyl-(1 ! 6)-2-(acetylamino)-3,4-di-O-benzoyl-2-deoxy-b-d-glucopyranoside (13). A mix-
ture of 11 (300 mg, 0.42 mmol), trichloroacetimidate 12 (308 mg, 0.51 mmol), and powdered 4-ꢃ
molecular sieves in dry CH2Cl2 (12 ml) were stirred for 30 min at r.t. and then cooled to ꢀ 308. TMSOTf
(10 ml, 0.04 mmol) was added. After stirring at ꢀ 308 for 1 h, the mixture was warmed up to r.t. for
30 min. The reaction was quenched by addition of Et3N, and then the mixture was filtered. The filtrate

Helvetica Chimica Acta – Vol. 97 (2014)
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was concentrated and purified by CC (SiO2; petroleum ether/AcOEt 3 :1) to afford 13 (420 mg, 87%).
1
White solid. [a]2D7 ¼ þ46.5 (c ¼ 0.8, CHCl3). H-NMR (CDCl3, 600 MHz): 8.20 – 7.19 (m, 29 arom. H);
5.97 (d, J ¼ 7.8, HꢀC(1)); 5.86 (t, J ¼ 9.6, HꢀC(3)); 5.63 (dd, J ¼ 9.6, 7.0, HꢀC(2’’)); 5.59 – 5.55 (m,
HꢀC(4’’), NH); 5.13 (t, J ¼ 9.6, HꢀC(4)); 5.06 (t, J ¼ 9.6, HꢀC(3’’)); 4.99 (d, J ¼ 7.0, HꢀC(1’’)); 4.96 (dd,
J ¼ 9.1, 7.0, HꢀC(2’)); 4.65 (d, J ¼ 7.3, HꢀC(1’)); 4.44 – 4.31 (m, HꢀC(3’), HꢀC(4’), HaꢀC(5’), HaꢀC(5’’),
HaꢀC(6)); 4.09 (ddd, J ¼ 9.6, 7.8, 6.5, HꢀC(2)); 3.77 – 3.71 (m, HꢀC(5), HbꢀC(5’’), HbꢀC(6)); 3.73 (dd,
J ¼ 13.1, 2.9, HbꢀC(5’)); 3.67 (s, MeO); 1.87 (s, NHCOMe); 1.37, 1.59 (2s, 2 Me). 13C-NMR (CDCl3,
150 MHz): 170.1 (MeCONH); 166.7; 166.3; 165.9; 165.6; 165.3; 153.4; 150.2; 136.7; 136.5; 136.3; 133.3;
133.1; 132.9; 132.7; 132.6; 129.9; 129.7; 129.3; 128.6; 128.3; 127.9; 126.3; 118.9; 115.3; 110.5 (Me2C); 108.5
(C(1’)); 107.9 (C(1’’)); 105.2 (C(1)); 81.6 (C(2’)); 79.9 (C(5)); 78.6 (C(4’)); 77.9 (C(3’)); 77.7 (C(3)); 77.5
(C(2’’)); 73.6 (C(4)); 72.9 (C(3’’)); 71.5 (C(4’’)); 69.7 (C(6)); 67.0 (C(5’)); 65.9 (C(5’’)); 55.7 (MeO); 55.2
(C(2)); 28.3 (Me2C); 26.7 (Me2C); 21.1 (MeCONH). HR-ESI-MS: 1174.3691 ([M þ Naþ],
C63H61NNaOþ20 ; calc. 1174.3679).
4-Methoxyphenyl 2,3,4-Tri-O-benzoyl-b-d-xylopyranosyl-(1 ! 2)-a-l-arabinopyranosyl-(1 ! 6)-2-
(acetylamino)-3,4-di-O-benzoyl-2-deoxy-b-d-glucopyranoside (14’).
A mixture of 13 (200 mg,
0.17 mmol) and TsOH (30 mg, 0.17 mmol) in CH2Cl2/MeOH 1:2 (12 ml) was stirred at r.t. When TLC
(petroleum ether/AcOEt 3 :1) showed that deprotection was complete, Et3N (0.1 ml) was added, and the
mixture was concentrated and purified by CC (SiO2; petroleum ether/AcOEt 1.5 :1) to afford 14’
(168 mg, 89%). White solid. [a]2D7 ¼ þ38.9 (c ¼ 0.6, CHCl3). 1H-NMR (CDCl3, 600 MHz): 8.10 – 7.10 (m,
29 arom. H); 5.96 (d, J ¼ 7.8, HꢀC(1)); 5.87 (t, J ¼ 9.6, HꢀC(3)); 5.65 (dd, J ¼ 9.6, 7.0, HꢀC(2’’)); 5.50 –
5.41 (m, HꢀC(4’’), NH); 5.16 (t, J ¼ 9.6, HꢀC(4)); 5.03 (t, J ¼ 9.7, HꢀC(3’’)); 4.95 (t, J ¼ 3.7, HꢀC(2’));
4.91 (d, J ¼ 6.9, HꢀC(1’’)); 4.61 (br. s, HꢀC(1’)); 4.46 (dd, J ¼ 12.7, 3.7, HaꢀC(5’’)); 4.40 – 4.31 (m,
HꢀC(3’), HꢀC(4’), HaꢀC(6)); 4.07 (ddd, J ¼ 9.6, 7.8, 6.3, HꢀC(2)); 3.91 (d, J ¼ 8.3, HOꢀC(4’)); 3.90 – 3.80
(m, HꢀC(5), HaꢀC(5’), HbꢀC(5’’), HbꢀC(6)); 3.66 (dd, J ¼ 13.3, 3.5, HbꢀC(5’)); 3.65 (d, J ¼ 9.1,
HOꢀC(3’)); 3.64 (s, MeO); 1.85 (s, NHCOMe). 13C-NMR (CDCl3, 150 MHz): 170.3 (MeCONH); 166.9;
166.3; 165.8; 165.6; 165.2; 153.4; 150.12; 136.7; 136.5; 136.3; 133.3; 132.9; 132.5; 132.6; 129.8; 129.7; 129.3;
128.6; 128.2; 127.7; 126.3; 119.0; 115.5; 108.3 (C(1’)); 107.7 (C(1’’)); 104.9 (C(1)); 82.3 (C(2’)); 79.9 (C(5));
78.3 (C(3’)); 77.6 (C(3)); 76.1 (C(2’’)); 73.6 (C(4’)); 72.8 (C(3’’)); 71.5 (C(4’’)); 68.3 (C(4)); 67.0 (C(6));
65.6 (C(5’)); 63.2 (C(5’’)); 56.1 (MeO); 55.4 (C(2)); 21.1 (MeCONH). HR-ESI-MS: 1164.3387 ([M þ
Naþ], C60H57NNaO2þ0 ; calc. 1134.3365).
4-Methoxyphenyl b-d-Xylopyranosyl-(1 ! 2)-a-l-arabinopyranosyl-(1 ! 6)-2-(acetylamino)-2-de-
oxy-b-d-glucopyranoside (1). To a soln. of 14’ (100 mg, 0.09 mmol) in dry CH2Cl2/MeOH 1:2 (20 ml)
was added a freshly prepared of MeONa in MeOH soln. (1.0m, 0.20 ml). The mixture was stirred at r.t. for
5 h and neutralized with Dowex Hþ resin to pH 7, and then filtered. The filtrate was concentrated, and the
resulting residue was subjected to CC (SiO2; CHCl3/MeOH 10 :1) to give the target trisaccharide 1
(43 mg, 80%). White amorphous solids. [a]2D7 ¼ þ45.7 (c ¼ 0.5, CHCl3). H-NMR (CD3OD, 600 MHz):
1
6.94 (d, J ¼ 9.0, 2 arom. H); 6.83 (d, J ¼ 9.0, 2 arom. H); 4.52 (d, J ¼ 8.0, HꢀC(1)); 4.49 (d, J ¼ 7.0,
HꢀC(1’’)); 4.39 (d, J ¼ 5.7, HꢀC(1’)); 4.09 (t, J ¼ 9.7, HꢀC(3)); 4.05 (t, J ¼ 7.3, HꢀC(2’’)); 3.96 – 3.91 (m,
HꢀC(3’’), HꢀC(4’’)); 3.89 (t, J ¼ 9.7, HꢀC(4)); 3.78 – 3.69 (m, HꢀC(2’), HꢀC(4’), HaꢀC(5’), HbꢀC(5’),
HaꢀC(5’’)); 3.65 (s, MeO); 3.60 – 3.55 (m, HꢀC(2), HꢀC(3’), HaꢀC(6)); 3.47 – 3.41 (m, CH2(5),
HbꢀC(5’’), HbꢀC(6)); 1.91 (s, NHCOMe). 13C-NMR (CD3OD, 150 MHz): 171.1 (MeCONH); 154.7;
150.5; 117.0; 115.1; 105.7 (C(1’)); 104.3 (C(1’’)); 103.5 (C(1)); 83.6 (C(2’)); 81.3 (C(5)); 78.6 (C(3’’)); 77.6
(C(3’)); 76.1 (C(2’’)); 73.6 (C(3)); 72.8 (C(4)); 72.0 (C(4’’)); 71.5 (C(4’)); 69.6 (C(6)); 68.7 (C(5’’)); 67.5
(C(5’)); 56.3 (MeO); 55.7 (C(2)); 22.3 (MeCONH). HR-ESI-MS: 614.2079 ([M þ Naþ], C25H37NNaO1þ5
;
calc. 614.2054).
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Received May 8, 2013