Widely applicable deprotection method of 2,2,2-trichloroethoxycarbonyl (Troc) group using tetrabutylammonium fluoride

Article abstract of DOI:10.1080/07328303.2010.512405

The N-Troc (2,2,2-trichloroethoxycarbonyl) groups in glucosamine and muramic acid derivatives were removed by treatment with tetrabutylammonium fluoride (TBAF) under mild conditions. The use of Troc protection for the amino group in aminosugars such as gl

Full text of DOI:10.1080/07328303.2010.512405

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Widely Applicable Deprotection Method
of 2,2,2-Trichloroethoxycarbonyl (Troc)
Group Using Tetrabutylammonium
Fluoride
Cheng-yuan Huang a , Ning Wang a , Katsumasa Fujiki a , Yuji Otsuka
a , Masao Akamatsu a , Yukari Fujimoto a & Koichi Fukase a
a Department of Chemistry, Graduate School of Science, Osaka
University, Toyonaka, Osaka, 560-0043, Japan
Published online: 29 Sep 2010.
To cite this article: Cheng-yuan Huang , Ning Wang , Katsumasa Fujiki , Yuji Otsuka , Masao
Akamatsu , Yukari Fujimoto & Koichi Fukase (2010) Widely Applicable Deprotection Method of 2,2,2-
Trichloroethoxycarbonyl (Troc) Group Using Tetrabutylammonium Fluoride, Journal of Carbohydrate
Chemistry, 29:6, 289-298, DOI: 10.1080/07328303.2010.512405
To link to this article: http://dx.doi.org/10.1080/07328303.2010.512405
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Journal of Carbohydrate Chemistry, 29:289–298, 2010
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2010.512405
Widely Applicable
Deprotection Method of
2,2,2-Trichloroethoxycarbonyl
(Troc) Group Using
Tetrabutylammonium Fluoride
Cheng-yuan Huang, Ning Wang, Katsumasa Fujiki, Yuji Otsuka,
Masao Akamatsu, Yukari Fujimoto, and Koichi Fukase
Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka,
Osaka 560-0043, Japan
The N-Troc (2,2,2-trichloroethoxycarbonyl) groups in glucosamine and muramic acid
derivatives were removed by treatment with tetrabutylammonium fluoride (TBAF) un-
der mild conditions. The use of Troc protection for the amino group in aminosugars
such as glucosamine is increasing the importance for selective and efficient glycosyla-
tion, and the cleavage method described here will expand the available opportunities
for using the Troc group in the preparation of a variety of glycans. This cleavage is espe-
cially advantageous for compounds that are labile or may be decomposed under acidic
conditions, strong basic conditions, or reductive conditions.
Keywords 2,2,2-Trichloroethoxycarbonyl group; Tetrabutylammonium fluoride;
Glucosamine; Deprotection.
INTRODUCTION
The 2,2,2-trichloroethoxycarbonyl (Troc) group was first introduced in organic
synthesis by Woodward in 1966.[1] It is a stable protecting group for hydroxyl
and amino groups,[2] and it has been widely used in organic synthesis, includ-
ing oligosaccharide synthesis. For example, β-selective glycosylation is eas-
ily achieved by the effect of neighboring group participation of the 2-N-Troc
Received February 12, 2010; accepted July 28, 2010.
Address correspondence to Koichi Fukase and Yukari Fujimoto, Department of Chem-
istry, Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan.
E-mail: koichi@chem.sci.osaka-u.ac.jp
289

C-y. Huang et al.
290
group.[3] The Troc group is usually removed by a reductive elimination process.
Several deprotection conditions have been published, such as Zn or Zn-Cu in
AcOH, Zn-Pb in AcOH, Cd-Pd in AcOH, Li in liquid NH3, SmI2 in THF, Cd in
AcOH-DMF, electrolysis,[2] Zn-N-methylimidazole,[4] mischmetal (50% Ce, 25%
La, 16% Nd, 6% Pr) with TMSCl,[5] and (Bu3Sn)2 in DMF.[6]
When the reductive conditions, such as Zn or Zn-Cu, are used, reductive
substitution of a chlorine atom with a hydrogen one may occur as a side re-
action. For the deprotection of Troc groups in an oligosaccharide, this chlorine
elimination often causes a problem in obtaining a satisfactory yield. The re-
ductive methods often use acidic conditions, which restrict their application
to acid-stable compounds. The Zn-N-methylimidazole[4] or mischemetal with
TMSCl[5] was developed recently as a milder condition to avoid the acidic con-
ditions. In addition, most of these reactions are carried out under heteroge-
neous conditions except (Bu3Sn)2, and in these cases it is difficult to apply
these methods to solid-phase synthesis. Therefore, we have developed a new
method for the removal of the Troc group under mild conditions in a homo-
geneous reaction using tetrabutylammonium fluoride (TBAF). Although it is
assumed that the Troc group may be removed under basic conditions, such
conditions have not been reported to our knowledge, except under particular
circumstances[7] or in Coudert’s trial for carbamates.[8] Coudert and co-workers
reported the deprotection of carbamates with TBAF; however, the conditions
were rather harsh. The carbamates of ethyl, allyl (Alloc), benzyl (Z), and t-butyl
(Boc) for amino protecting groups were only cleaved by using a large excess of
TBAF under reflux conditions with THF for several hours. Only phenyl carba-
mate was removable at rt, though. Hence, we tried the Troc deprotection with
TBAF, and also obtained results with LiOH.
RESULTS AND DISCUSSION
We first examined the cleavage of the N-Troc group from the glucosamine
derivative 1 with TBAF. When the compound 1 was treated with 1 M TBAF
in THF at rt, followed by acetylation, the desired product 2 was obtained in
97% yield. The deprotection reaction was next applied to some different glu-
cosamine derivatives, and they all gave good yields (Table 1). Other functional
groups, such as the acetal group (benzylidene group in compounds 1, 3, and 5),
ester groups (in compounds 3 and 5), an amide group (in compound 2), and the
relatively stable ethers (benzyl ether in 1, 5, and 7), were not affected.
Compound 3 is a muramic acid linked to a dipeptide, which contains a car-
boxylic acid protected with a benzyl ester. Deprotection of the 2-N-Troc group
of compound 3 with TBAF gave a good yield in 90% after acetylation. The
4-O-acylated glucosamine derivative 5 and the 4,6-O-dihydroxy glucosamine

Deprotection Method of 2,2,2-trichloroethoxycarbonyl Group
291
Table 1: Cleavage of the Troc group using TBAF
Entry
Substrate
Product
Yield
1
2
1 R=Bn
2 R=Bn
97%
90%∗
3
4
77%
78%
∗: Reaction with additional 2 equiv. acetic acid.

C-y. Huang et al.
292
derivative 7 also gave satisfactory yields in 77% and 78% (in two steps), re-
spectively.
In the case of a muramic acid derivative 9,[9] which has a relatively reactive
ethyl ester, it gave the lactam 10 formed by the intramolecular condensation
between the liberated amino group and the ester (Sch. 1). This reaction con-
dition might be useful for other intramolecular lactam formation and peptide
bond formation under a mild condition.
We also used lithium hydroxide as the base (Sch. 2). N-Troc muramic acid
derivative 11[10] was treated with LiOH in a mixed THF/dioxane/water solu-
tion; after stirring at rt for 3 h, the mixture was neutralized by addition of
Dowex 50W ion exchange resin. Then the free amino group was protected with
the acetyl group to give muramic acid derivative 12 in good yield (87% in two
steps). The cleavage reaction in compound 9 also proceeded in good yield (90%
in two steps, including acetylation). In both cases, no lactam products were
found in the reaction. On the other hand, when the lactam 10 was treated
with LiOH under similar reaction conditions, the lactam ring was found to
open, followed by acetylation of the intermediate to give the compound 13.
In conclusion, we have developed a mild and efficient methodology for re-
moving the Troc protecting group. This method tolerates several other types of
functional groups. It may further be applied to solid-phase synthesis and other
organic syntheses.
EXPERIMENTAL
General Procedures
1H NMR spectra were recorded at 500 MHz using a JEOL ECA 500 spec-
trometer. The chemical shifts in CDCl3 are given in δ values from tetramethyl-
silane as an internal standard. ESI-TOF mass spectrometry was carried out
using an Applied Biosystem Mariner Biospectrometry Workstation. MALDI-
TOF mass spectrometry was carried out using an Applied Biosystem Voyager
Elite XL (Matrix: α-Cyano-4-hydroxycinnamic acid). ESI-QTOF mass spec-
trometry was carried out using a Waters-Micromass Q-Tof micro. Elemental
analyses were performed with Yanaco CHN corder MT-6. Silica gel column
chromatography was carried out using Kieselgel 60 (Merck, 0.040–0.063 mm)
at medium pressure (2–4 kg/cm2). All other reagents and solvents used were
purchased from commercial sources.
General Reaction Procedure of the Troc Group Deprotection
with TBAF
Compound 1 (26.2 mg, 0.05 mmol) was dissolved in THF (0.4 mL), and
then 1 M TBAF in THF (0.2 mL) was added. The mixture was stirred at rt

293

294

Deprotection Method of 2,2,2-trichloroethoxycarbonyl Group
295
for 3 h. The mixture was diluted with ethyl acetate, washed with water and
brine, and dried over Na2SO4. The solvent was removed under vacuum, and
the residue was treated with a pyridine:acetic anhydride 1:1 solution (1 mL).
The mixture was stirred at rt for 1 h. The solvent was removed under vacuum,
followed by coevaporation with toluene (×4). The residue was purified by flash
silica gel column chromatography to give the product 2 19.5 mg (yiled 97%). 1H
NMR (500 MHz, CDCl3) δ = 7.46–7.45 (m, 2H, (C6H5)-CH2-), 7.36–7.33 (m, 8H,
(C6H5)-CH2-), 7.22–7.21 (d, J = 7.9 Hz, 1H, D-isoGln-NH), 7.09–7.08 (d, J = 6.3
Hz, 1H, L-Ala-NH), 6.28–6.26 (d, J = 9.0 Hz, 1H, H-1), 5.94–5.85 (m, 1H, -CH2-
CH CH2), 5.56 (s, 1H, Ph-CH ), 5.31–5.24 (m, 3H, -CH2-CH CH2, Ph-CH2-),
4.48–4.46 (m, 1H, D-isoGln-αH), 4.30–4.25 (m, 2H, H2, H5), 4.20–4.13 (m, 2H, -
CH2-CH CH2, L-Ala-αH), 4.08–4.07 (q, J = 6.7 Hz, 1H, Lac-αH), 4.02–3.99 (m,
1H, -CH2-CH CH2), 3.86–3.81 (m, 1H, H-4), 3.78–3.74 (m, 1H, H-6), 3.70–3.63
(m, 2H, H-3, H-6), 2.60–2.47 (m, 2H, D-isoGln-γH), 2.29–2.20 (m, 1H, D-
isoGln-βH), 2.09–2.01 (m, 4H, D-isoGln-βH, N-Ac), 1.41–1.36 (m, 6H, L-Ala-
βH, Lac-Me). 13C NMR (125 MHz, CDCl3) δ = 169.7, 138.6, 137.4, 133.4, 128.9,
128.3, 128.2, 127.9, 127.6, 126.0, 117.9, 101.3, 97.4, 82.8, 76.0, 74.0, 68.9, 68.4,
62.9, 52.4, 23.3. HRMS (ESI-QTOF) for C25H30NO6 [M+H]+ calcd 440.2073;
+
found 440.2061. [α]D = +121.3◦ (c 0.23, CHCl3). Anal. Calcd for C25H29NO6: C,
68.32%; H, 6.65%; N, 3.19%. Found: C, 68.02%; H, 6.48%; N, 3.19%.
Compounds 4, 6, 8, and 10 were also synthesized with a similar procedure,
and the spectroscopic data were as follows:
4: 1H NMR (500 MHz, CDCl3): δ = 7.46–7.45 (m, 2H, (C6H5)-CH2-),
7.36–7.33 (m, 8H, ((C6H5)-CH2-), 7.22–7.21 (d, J = 7.9 Hz, 1H, D-isoGln-
NH), 7.09–7.08 (d, J = 6.3 Hz, 1H, L-Ala-NH), 6.28–6.26 (d, J = 9.0 Hz,
1H, H1), 5.94–5.85 (m, 1H, -CH2-CH CH2), 5.56 (s, 1H, Ph-CH ), 5.31–5.24
(m, 3H, -CH2-CH CH2, Ph-CH2-), 4.48–4.46 (m, 1H, D-isoGln-αH), 4.30–4.25
(m, 2H, H-2, H-5), 4.20–4.13 (m, 2H, -CH2-CH CH2, L-Ala-αH), 4.08–4.07
(q, J = 6.7 Hz, 1H, Lac-αH), 4.02–3.99 (m, 1H, -CH2-CH CH2), 3.86–3.81
(m, 1H, H-4), 3.78–3.74 (m, 1H, H-6), 3.70–3.63 (m, 2H, H-3, H-6), 2.60–2.47
(m, 2H, D-isoGln-γH), 2.29–2.20 (m, 1H, D-isoGln-βH), 2.09–2.01 (m, 4H, D-
isoGln-βH, N-Ac), 1.41–1.36 (m, 6H, L-Ala-βH, Lac-Me); 13C NMR (125 MHz,
CDCl3): δ = 174.1, 173.8, 173.3, 172.1, 170.7, 137.1, 135.6, 133.1, 129.1, 128.6,
128.4, 128.3, 128.2, 126.0, 118.7, 101.5, 97.2, 81.3, 78.1, 76.8, 68.8, 68.7, 66.7,
63.0, 53.1, 52+.7, 50.0, 30.8, 26.4, 23.6, 19.4, 16.8. ESI-TOF MS (positive) for
C36H47N4O11 [M+H]+ calcd 711.3241; found 711.43. [α]D = +66.0◦ (c 0.18,
CHCl3). Anal. Calcd for C36H46N4O11: C, 60.83%; H, 6.52%; N, 7.88%. Found:
C, 60.46%; H, 6.51%; N, 7.92%.
6: 1H NMR (500 MHz, CDCl3): δ = 7.46–7.22 (m, 10H, C6H5CH2-, C6H5CH
), 5.93–5.85 (m, 1H, -CH2CH CH2), 5.79 (d, J = 9.3 Hz, 1H, -NHAc), 5.49 (s,
1H, PhCH ), 5.37 (t, J = 10.1 Hz, 1H, H-3), 5.32–5.23 (m, 2H, -CH2CH CH2),
4.89 (d, J = 3.7 Hz, 1H, H-1), 4.51, 4.41 (d, J = 11.7 Hz, each 1H, PhCH2-
), 4.35 (dt, J = 10.1, 3.7 Hz, 1H, H-2), 4.28 (dd, J = 10.2, 4.7 Hz, 1H, H-6),
4.20, 4.00 (m, each 1H, -CH2CH CH2), 3.93 (dt, J = 9.9, 4.7 Hz, 1H, H-5),

C-y. Huang et al.
296
3.81–3.69 (m, 3H, H-4, H-6, -CH(OBn)-), 2.69, 2.45 (dd, J = 15.2, 6.1 Hz, each
1H, α-H), 1.91 (s, 3H, -COCH3), 1.58–1.11 (m, 12H, -(CH2)6-), 0.86 (t, J = 7.1
Hz, 3H, -CH2CH3). 13C NMR (125 MHz, CDCl3) δ = 172.2, 169.9, 138.6, 137.0,
133.2, 129.1, 128.3, 128.2, 127.7, 127.5, 126.1, 118.3, 101.6, 97.2, 79.1, 75.5,
71.1, 70.2, 68.9, 68.7, 63.0, 52.6, 39.6, 34.5, 31.8, 29.5, 29.3, 25.1, 23.2, 22.6,
14.1. MALDI-TOF MS (positive) for C35H47NNaO8 [M+Na]+ calcd 632.3199;
+
found 632.4486. HRMS (ESI-QTOF) (positive) for C35H48NO8 [M+H]+ calcd
+
610.3380; found 610.3371. [α]D = +38.9◦ (c 0.28, CHCl3). Anal. Calcd for
C35H47NO8·H2O: C, 66.96%; H, 7.87%; N, 2.23%. Found: C, 66.80%; H, 7.87%;
N, 2.16%.
8: 1H NMR (500 MHz, CDCl3): δ = 7.35–7.25 (m, 5H, C6H5CH2-), 5.92–5.82
(m, 1H, -CH2CH CH2), 5.33 (d, J = 9.3 Hz, 1H, -NHAc), 5.30–5.22 (m, 2H, -
CH2CH CH2), 5.17 (dd, J = 10.1, 9.3 Hz, 1H, H-4), 4.89 (d, J = 3.6 Hz, 1H,
H-1), 4.63, 4.54 (d, J = 11.5 Hz, each 1H, PhCH2-), 4.37 (ddd, J = 10.7, 9.3,
3.6 Hz, 1H, H-2), 4.20 (dd, J = 12.3, 5.0 Hz, 1H, H-6), 4.16, 3.99 (m, each
1H, -CH2CH CH2), 4.09 (dd, J = 12.3, 2.5 Hz, 1H, H-6), 3.90 (ddd, J = 10.1,
5.0, 2.5 Hz, 1H, H-5), 3.77 (dd, J = 10.7, 9.3 Hz, 1H, H-3), 2.09 (s, 3H, -
COCH3), 2.03 (s, 3H, -COCH3), 1.88 (s, 3H, -COCH3). 13C NMR (125 MHz,
CDCl3) δ = 170.8, 169.6, 169.4, 138.0, 133.3, 128.5, 128.0, 127.9, 118.1, 96.8,
77.6, 72.8, 69.9, 6+8.6, 68.4, 62.4, 51.7, 23.4, 20.8, 20.77. HRMS (ESI-QTOF)
for C22H29NNaO8 [M+Na]+ calcd 458.1791; found 458.1722. [α]D = +98.8◦
(c 0.25, CHCl3). Anal. Calcd for C22H29NO8·0.6H2O: C, 59.21%; H, 6.82%; N,
3.14%. Found: C, 59.18%; H, 6.92%; N, 2.95%.
10: 1H NMR (500 MHz, CDCl3): δ = 7.55–7.34 (m, 5H, C6H5CH ), 6.06 (br
s, 1H, -NH), 5.95–5.86 (m, 1H, -CH2CH CH2), 5.58 (s, 1H, PhCH ), 5.35–5.25
(m, 2H, -CH2CH CH2), 4.88 (d, J = 3.6 Hz, 1H, H-1), 4.33 (q, J = 6.9 Hz,
1H, Lac-αH), 4.28 (dd, J = 10.3, 4.8 Hz, 1H, H-6), 4.24, 4.02 (m, each 1H, -
CH2CH CH2), 4.10 (t, J = 9.4 Hz, 1H, H-4), 3.96 (dt, J = 9.4, 4.8 Hz, 1H,
H-5), 3.80 (t, J = 10.3 Hz, 1H, H-6), 3.77 (t, J = 9.3 Hz, 1H, H-3), 3.66
(dd, J = 9.3, 3.6 Hz, 1H, H-2), 1.50 (d, J = 6.9 Hz, 3H, CH3- of Lac). 13
C
NMR (125 MHz, CDCl3) δ = 171.8, 136.9, 133.2, 129.2, 128.3, 126.3, 118.2,
102.0, 96.2,+79.1, 74.4, 72.3, 69.2, 68.8, 63.9, 56.1, 17.8. HRMS (ESI-QTOF) for
C19H24NO6 [M+H]+ calcd 362.1604; found 362.1603. [α]D = +91.3◦ (c 0.27,
CHCl3). Anal. Calcd for C19H23NO6·0.7H2O: C, 61.02%; H, 6.58%; N, 3.75%.
Found: C, 60.98%; H, 6.50%; N, 3.62%.
General Reaction Procedure of the Troc Group
Deprotection with LiOH
Compound 11 (200.7 mg, 0.287 mmol) was dissolved in a mixture of
THF:dioxane:water = 4:2:1 (9 mL), and then LiOH (65.9 mg, 1.57 mmol) was
added. The mixture was stirred at rt for 3 h. The solution was neutralized
by adding Dowex 50W (H+) resin (260 mg) and filtered, and the filtrate was
evaporated under vacuum. The crude residue (142.9 mg) was treated with a

Deprotection Method of 2,2,2-trichloroethoxycarbonyl Group
297
pyridine:acetic anhydride 1:1 solution (10.8 mL). The mixture was stirred at
rt for 1 h. The solvent was removed under vacuum, followed by coevaporation
with toluene (×4). The residue was purified by flash silica gel column chro-
1
matography to give the product 12 131.8 mg (yield 87%). H NMR (500 MHz,
CDCl3:CD3OD, 9:1) δ = 7.46–7.36 (m, 5H, ArH), 5.56 (s, 1H, Ph-CH ), 4.69 (d,
J = 7.9 Hz, 1H, H-1), 4.31 (dd, J = 4.85 Hz, J = 10.45 Hz, 1H, H-6), 4.24 (q,
J = 6.75 Hz, 1H, Lac-αH), 3.95–3.91 (m, 1H, PEG-H-1), 3.82–3.77 (m, 3H, H-6,
H-3, H-2), 3.74–3.71 (m, 1H, PEG-H-1), 3.70–3.63 (m, 8H, PEG-H-2, PEG-H-3,
PEG-H-4, PEG-H-5), 3.44–3.38 (m, 4H, H-5, H-4, PEG-H-6), 2.00 (s, 3H, CH3-
CO-), 1.38 (d, J = 6.9 Hz, 3H, Lac-CH3); 13C NMR (125 MHz, CDCl3:CD3OD,
9:1) δ = 176.5, 172.7, 137.0, 128.9, 128.1, 125.8, 101.7, 101.1, 81.8, 78.1, 70.40,
70.36, 70.34, 69.8, 68.7, 68.5, 66.0, 55.9, 55.83, 50.5, 22.8, 18.8; ESI-TOF-MS
(m/z): [M+H]+ calcd. for C24H35N4O10, 539.23; found 539.23. [M+Na]+ calcd.
for C24H34N4O10Na, 561.23; found 561.21. [M-H]− calcd. for C24H33N4O10,
537.23; found 537.23. [α]D = –28.3◦ (c 1.03, CHCl3:MeOH = 9:1). Anal. Calcd
for C24H34N4O10: C, 53.52%; H, 6.36%; N, 10.40%. Found: C, 53.01%; H, 6.21%;
N, 9.83%.
Compound 13 was also synthesized with a similar procedure, and the spec-
troscopic data were as follows:
13: 1H NMR (500 MHz, CDCl3:CD3OD = 9:1): δ = 7.50–7.23 (m, 5H,
C6H5CH ), 5.91–5.81 (m, 1H, -CH2CH CH2), 5.58 (s, 1H, PhCH ), 5.30–5.00
(m, 3H, H-1, -CH2CH = CH2), 4.33 (q, J = 6.6 Hz, 1H, Lac−αH), 4.24 (dd, J =
9.5, 3.9 Hz, 1H, H-6), 4.15, 3.99 (m, each 1H, -CH2CH CH2), 3.93 (dd, J = 10.3,
2.7 Hz, 1H, H-2), 3.88–3.60 (m, 4H, H-3, H-4, H-5, H-6), 2.01 (s, 3H, -COCH3),
1.41 (d, J = 6.6 Hz, 3H, Lac−CH3). 13C NMR (125 MHz, CDCl3:CD3OD =
9:1) δ = 179.0, 172.2, 137.1, 133.5, 128.8, 128.0, 125.7, 117.3, 101.2, 96.6,
82.3, 75.2, 68.7, 68.6, 62.9, 54.2, 29.5, 22.3, 18.7. ESI-TOF MS (positive) for
C21H27NO8Na+ [M+Na]+ calcd 444.1634; found 444.1740. HRMS (ESI-QTOF)
(positive) for C21H28NO8 [M+H]+ calcd 422.1815; found 422.1812. [α]D
=
+
+83.0◦ (c 0.23, CHCl3). Anal. Calcd for C21H27NO8·0.5H2O: C, 58.60%; H,
6.36%; N, 3.25%. Found: C, 58.66%; H, 6.70%; N, 2.95%.
ACKNOWLEDGMENTS
This work was supported in part by Grants in Aid for Scientific Research (No.
19310144) from the Japan Society for the Promotion of Science, as well as a
grant from the Osaka University G-COE program “Global Education and Re-
search Center for Bio-Environmental Chemistry” (to CH).
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10. Compound 11 was obtained with the glycosylataion of 4,6-O-benzylidene 2-N-Troc
muramic acid (4,6-benzylidene-MurNTroc) with the same procedure with the synthe-
sis of 9.[9] Namely, 4,6-benzylidene-MurNTroc (44.9 mg, 0.083 mmol) and CsCO3 (17.3
mg, 0.053 mmol) were dispersed in dry CH2Cl2 (0.9 mL). To this mixture was added
CCl3CN (0.083 mL, 0.83 mmol), and the mixture was stirred for 3.5 h. The reaction
mixture was then filtrated with celite, and the solvent was removed in vacuo. The
obtained trichloroacetimidate compound was used after lyophilization with benzene,
without further purification. The imidate (60.8 mg), HO(CH2)2O(CH2)2O(CH2)N3 (44.2
mg, 0.252 mmol), and MS 4A were added in CH2Cl2 (2.7 mL) and cooled to –15◦C. To
the reaction mixture, a solution of TMSOTf (1.6 µL, 8.7 µmol) in CH2Cl2 (0.08 mL) was
added. The mixture was stirred for 1.5 h, quenched with sat. NaHCO3aq, and then fil-
trated. The combined organic layer was washed with sat. NaHCO3aq. and then brine.
The solvent was removed in vacuo, and the crude material was purified by silica gel
flash chromatography (toluene:AcOEt = 4:1) to give 11 (51.3 mg, 88%) as a white solid.
1H NMR (500 MHz, CDCl3): δ = 7.46–7.36 (m, 5H, C6H5CH ), 5.56 (s, 1H, PhCH ),
4.79–4.73 (m, 2H, -CO-O-CH2-CCl3), 4.67 (d, J = 8.0 Hz, 1H, H-1), 4.50 (q, J = 7.0 Hz,
1H, Lac-αH), 4.34 (dd, J = 4.9, 5.7 Hz, 1H, H-6), 4.23–4.09 (m, 2H, -CO-O-CH2-CH3),
3.96–3.92 (m, 1H, PEG-H-1), 3.86–3.76 (m, 4H, H-6, H-3, H-2), 3.75–3.63 (m, 7H, H-2,
PEG-H-3, PEG-H-4, PEG-H-5), 3.60–3.55 (m, 1H, H-4), 3.44–3.39 (m, 3H, H-5, PEG-H-
6), 1.39 (d, J = 6.85 Hz, 3H, Lac-CH3). ESI-TOF MS for C27H38Cl3N4O11, [M+H]+ calcd
699.15, found 699.13.