(2-Azidomethyl)phenylacetyl as a new, reductively cleavable protecting group for hydroxyl groups in carbohydrate synthesis

Article abstract of DOI:10.1016/S0008-6215(01)00292-0

The (2-azidomethyl)phenylacetyl group (AMPA) is described as a new protecting group for carbohydrates. AMPA was introduced to carbohydrate hydroxyl groups in the presence of DCC, while its removal was conveniently achieved via Lindlar catalyst-catalyzed hydrogenation that had no influence on other protecting groups including benzyl, acyl, acetal and ketal.

Full text of DOI:10.1016/S0008-6215(01)00292-0

Carbohydrate Research 337 (2002) 87–91
www.elsevier.com/locate/carres
(2-Azidomethyl)phenylacetyl as a new, reductively cleavable
protecting group for hydroxyl groups in carbohydrate synthesis
Jinghua Xu, Zhongwu Guo*
Department of Chemistry, Case Western Reser6e Uni6ersity, 10900 Euclid A6enue, Cle6eland, OH 44106, USA
Received 31 August 2001; accepted 24 October 2001
Abstract
The (2-azidomethyl)phenylacetyl group (AMPA) is described as a new protecting group for carbohydrates. AMPA was
introduced to carbohydrate hydroxyl groups in the presence of DCC, while its removal was conveniently achieved via Lindlar
catalyst-catalyzed hydrogenation that had no influence on other protecting groups including benzyl, acyl, acetal and ketal. © 2002
Elsevier Science Ltd. All rights reserved.
Keywords: Carbohydrates; Protecting group; (2-Azidomethyl)phenylacetyl; Reductive cleavage
1. Introduction
used as the protecting group of hydroxyls in oligosac-
charide synthesis,6–8 was designed according to this
mechanism. It can be selectively removed by reduction
of the azido group to a free amino group that attacks
the neighboring ester bond to release the alcohol and
g-lactam (Scheme 1). Drawbacks of 4-azidobutanoyl
are that its removal needs prolonged heating and that
the yield of the deprotection step is generally low.6–8
Herein we report a new protecting group, (2-azi-
domethyl)phenylacetyl (AMPA), which can be easily
removed in quantitative yield through the selective re-
duction of its azido group. Thus, ‘assisted cleavage’ of
AMPA can be achieved under very mild conditions.
Successful strategies for oligosaccharide synthesis re-
quire sophisticated methods for the differentiation of
numerous hydroxyl groups on the sugar rings. For this
reason, an array of protecting groups, such as acyls,
alkyls, acetals and ketals, have been introduced.1,2 Nev-
ertheless, given the remarkable complexity of oligosac-
charide structures, the demands for new, versatile
protecting methods for hydroxyl groups still persist in
carbohydrate chemistry.
‘Assisted cleavage’, i.e., cleavage of a bond via in-
tramolecular attack induced by the selective activation
of a group in the molecule, has found its applications in
the design of special protecting groups in organic chem-
istry.2–6 For instance, 4-azidobutanoyl, which has been
2. Results and discussion
As shown in Scheme 2, reduction of the azido group
in the ester of AMPA (1), followed by intramolecular
cyclization, will give a d-lactam 3 and the free alcohol.
Since intramolecular cylclization to form d-lactams is
the most favorable process among lactamizations,9,10
we anticipated that AMPA might be more easily
cleaved than 4-azidobutanoyl upon reduction of the
azido group. Indeed, scattered reports suggest that d-
lactamization can occur spontaneously with high selec-
tivity.11,12 Moreover, the rigid conformation of AMPA,
which helps to lock the two involved groups adjacent to
Scheme 1. Removal of g-azidobutanoyl group via assisted
cleavage.
* Corresponding author. Tel.: +1-216-3683736; fax: +1-
216-3683006.
E-mail address: zxg5@po.cwru.edu (Z. Guo).
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00292-0

88
J. Xu, Z. Guo / Carbohydrate Research 337 (2002) 87–91
Scheme 2. AMPA as a protecting group and its reductive cleavage.
NMR spectrometry as well as by high-resolution mass
spectrometry.
each other, may further facilitate the intramolecular
attack, which is supported by recent reports of others.3–
5 Thus, AMPA was designed in this research as a
hydroxyl protecting group that can be easily removed
under mild reductive conditions.
Our synthesis of (2-azidomethyl)phenylacetic acid (5)
was achieved by a reported procedure (Scheme 3).11
The radical bromination of ethyl 2-methylphenylacetate
(4) with N-bromosuccinimide (NBS) and benzoyl per-
oxide, as well as the subsequent nucleophilic azido
substitution, was quite straightforward. However, the
saponification proved to be problematic, as it was very
sensitive to the workup procedures. After testing differ-
ent acids for neutralization of the reaction mixtures, we
found that only carbon dioxide could offer satisfactory
results (ꢀ50% yield). Nevertheless, the pure 5 obtained
after column chromatography was rather stable.
On the other hand, AMPA was readily cleaved by
selective reduction of the azido group. Thus, the expo-
sure of AMPA-protected monosaccharides 11–14 to
hydrogen and Lindlar catalyst in methanol at room
temperature for 3 h resulted in complete removal of
their AMPAs. The deprotected products could be very
easily separated from the d-lactam 3 by flash column
chromatography, for 3 had much higher polarity than
the alcoholic products in our study. Under these mild
reductive conditions, other protecting functions in the
molecules, such as benzyl, acetyl, ketal and acetal of
isopropylidene and benzylidene, were stable. Finally,
monosaccharides 6–8 were obtained in quantitative
yields, and 9 in 81% yield. For the latter, in addition to
9, methyl 2,3,6-tri-O-acetyl-a- -glucopyranoside (17)
D
was also obtained as a side product (19%), which was
probably formed by intramolecular acetyl migration.
After the successful introduction and removal of
AMPA to and from sugars, we then examined the
susceptibility of AMPA linkages to acidic and basic
treatment. It turned out that AMPA esters were quite
stable in the acidic conditions, e.g., 33% trifluroacetic
acid in dichloromethane or 0.25% H2SO4 water–MeOH
solution, used to deblock acetal or 5,6-ketal in 11 and
13 affording 10 (78%) and 3-O-[(2-azidomethyl)-
The protection of carbohydrate hydroxyl groups with
AMPA was realized via the condensation of 5 with
alcohols 6–10 by means of N,N-dicyclohexylcarbodi-
imide (DCC) and 4-dimethylaminopyridine (DMAP) in
dichloromethane at room temperature (Scheme 3 and
Table 1). All reactions gave excellent yields regardless
of whether the hydroxyl group was primary or sec-
ondary. Furthermore, these reaction conditions were
compatible with a variety of other protecting linkages,
including acetal, benzyl ether, ester and ketal. We have
also noticed that the reaction between 5 and a partially
blocked derivative of glucosamine 10 could be regiose-
lective under controlled conditions, e.g., use of only 1.1
equiv of 5 at 0 °C. Thus, AMPA was introduced to the
primary hydroxyl group in the presence of the sec-
ondary one to give a major product 15. Nonetheless, a
substantial amount (12%) of the 3,4,6-tri-O-(2-azi-
domethyl)phenylacetylated product 16 was still formed.
The structures of AMPA-protected products 11–16,
which were unknown compounds, were confirmed by
Table 1
AMPA-protected sugars 11–15 produced by esterification
Scheme 3. Synthesis of (2-azidomethyl)phenylacetic acid (5)
and protection of alcohols as AMPA esters. (a) (i) (BzO)2,
NBS, reflux; (ii) NaN3, DMF, rt; (iii) LiOH, THF, 0 °C to rt,
36% (overall); (b) ROH, DCC, DMAP, CH2Cl2, 0 °C to rt,
73–92%.

J. Xu, Z. Guo / Carbohydrate Research 337 (2002) 87–91
89
1
phenylacetyl]-1,2-O-isopropylidene-a-
D
-glucofuranose
73% over the two steps) as a colorless liquid: H NMR
(CDCl3) l 7.33–7.16 (m, 4 H, ArH), 4.47 (s, 2 H,
CH2N3), 4.15 (q, 2 H, J 7.2 Hz, OCH2Me), 3.72(s, 2 H,
CH2CO), 1.25 (t, 3 H, CH3).
(18, 80%), respectively. In contrast, but not surpris-
ingly, AMPA esters were labile under basic conditions,
e.g., to sodium methoxide in methanol, which is used to
remove acetyl groups.
To the solution of ethyl (2-azidomethyl)phenylacetate
(3.2 g, 14.6 mmol) in THF (22 mL) was added at 0 °C
a solution of LiOH (0.5 g, 21 mmol) in water (22 mL),
and the reaction mixture was stirred at 0 °C for 2.5 h.
Then, the reaction mixture was diluted with CH2Cl2
(100 mL) and brine (100 mL), which was followed by
addition of solid CO2 to neutralize the base. After the
organic layer was separated, the aqueous layer was
extracted with CH2Cl2 (2×100 mL). The organic solu-
tions were combined, and concentrated, and the final
product was purified by flash chromatography (eluent:
3:7 EtOAc–hexane) to afford (2-azidomethyl)-
phenylacetic acid (5, 1.34 g, 48%) as white solid: mp
In conclusion, AMPA has proved to be a highly
versatile protecting group for hydroxyl groups in carbo-
hydrate chemistry. During the process of preparing this
report, we noticed that Wada et al.13 developed a
similar protecting group. In view of the mild reaction
conditions, high yields and convenient workups during
the introduction and deprotection of AMPA esters, as
well as its compatibility with other protecting groups
commonly used, AMPA can be a generally useful pro-
tecting method in oligosaccharide synthesis.
1
3. Experimental
109–111 °C; H NMR (CDCl3) l 7.24–7.15 (m, 4 H,
ArH), 4.52 (s, 2 H, CH2N3), 3.60(s, 2 H, CH2CO).
General procedure for the introduction of AMPA onto
carbohydrate hydroxyl groups.—To a stirred solution of
5 (1.1 equiv), the monosaccharide 6–10 (1.0 equiv) and
DMAP (0.1 equiv) in dry CH2Cl2 was added DCC (1.2
equiv) at 0 °C. The mixture was stirred for 5 min at
0 °C and then 4–5 h at rt. The urea precipitates were
then filtered off, and the filtrate was concentrated to
dryness under vacuum. The residue was dissolved in
EtOAc which was sequentially washed with 0.5 M HCl,
satd aq NaHCO3 and brine. The solution was dried
over Na2SO4 and concentrated, and the crude product
was purified by column chromatography to afford the
AMPA-protected carbohydrates 11–15 (Table 1).
p-Methoxyphenyl 3-O-[(2-azidomethyl)phenylacetyl]-
General methods.—NMR spectra were recorded on a
Gemini-300 FT NMR spectrometer. Proton chemical
shifts are reported in ppm (l) downfield from tetra-
methylsilane (TMS). Coupling constants (J) are re-
ported in hertz (Hz). Carbon chemical shifts are
reported in ppm (l) in reference to solvent CDCl3 (l
77.00). Fast-atom bombardment mass spectra
(FABMS) were obtained with a Kratos MS-25RFA
spectrometer. Anhydrous solvents were purchased from
Aldrich and were directly used without further distilla-
tion. 1,2:5,6-Di-O-isopropylidene-a-
was also purchased from Aldrich. p-Methoxyphenyl
4,6-O-benzylidene-2-deoxy-2-phthalimido-b- -glucopy-
ranoside (6),14 methyl 2,3,4-tri-O-benzyl-a-
-glucopy-
D
-glucofuranose (8)
D
D
ranoside (7),15 and methyl 2,3,4-tri-O-acetyl-a-
D
-
4,6-O-benzylidene-2-deoxy-2-phthalimido-i-D-glucopy-
glucopyranoside (9)16 were prepared by the reported
procedures.
ranoside (11).—0.62 g, 92% yield; white solid: mp
122–125 °C; [h]2D5 +19° (c 1.0, CHCl3); eluent: 15:85
1
Preparation of (2-azidomethyl)phenylacetic acid
(5)10.—To a refluxing solution of ethyl 2-methylpheny-
lacetate (4, 3.5 g, 20 mmol) and benzoyl peroxide (0.04
g) in dry benzene (10 mL), was added a mixture of
N-bromosuccinimide (NBS, 3.4 g, 19 mmol) and ben-
zoyl peroxide (0.04 g) in portions within ca. 15 min. As
soon as the foam formed from the last addition of NBS
subsided, the flask was cooled down to rt and the
succinimide was filtered off and washed with benzene.
The filtrates were combined and condensed to yield
ethyl (2-bromomethyl)phenylacetate that was used di-
rectly in the next step.
EtOAc–hexane; H NMR (CDCl3): l 7.82–7.71 (m, 4
H, Phth ArH), 7.44–7.37 (m, 4 H, benzylidene ArH),
7.14–7.03 (m, 4 H, AMPA ArH), 6.84–6.71 (m, 4 H,
Mp ArH), 5.99 (dd, 1 H, J2,3 10.4, J3,4 9.1 Hz, 3-H),
5.91 (d, 1 H, J1,2 8.5 Hz, 1-H), 5.53 (s, 1 H, PhCH),
4.54 (dd, 1 H, 2-H), 4.42 (dd, 1 H, 4-H), 4.15, 4.08 (2 d,
2 H, J 14.0 Hz, CH2N3), 4.0–3.79 (m, 3 H, 5-H, 6a-H,
6b-H), 3.72 (s, 3 H, OMe), 3.63, 3.57 (2 d, 2 H, J 12.0
Hz, PhCH2CO); FABMS: 553 [M+−OMp], 525
[553−N2], 362 [553−AMPA−H, 100%]; HR-
FABMS: Calcd for C37H32N4O9 [M+], 676.2169.
Found, 676.2163.
NaN3 (2.6 g, 40 mmol) was added in one portion to
a solution of the above product in DMF (20 mL) at rt.
After stirring for 6 h, TLC showed complete reaction,
and the reaction mixture was partitioned between ether
and water. The organic layer was dried over Na2SO4
and then concentrated. The residue was purified by
column chromatography (eluent: 1:19 EtOAc–hexane)
to afford ethyl (2-azidomethyl)phenylacetate (3.2 g,
Methyl 6-O-[(2-azidomethyl)phenylacetyl]-2,3,4-tri-
O-benzyl-h- -glucopyranoside (12).—0.52 g, 82% yield;
D
colorless syrup; [h]2D5 +23.6° (c 0.9, CHCl3); eluent: 1:9
1
EtOAc–hexane; H NMR (CDCl3): l 7.38–7.18 (m, 19
H, ArH), 4.98, 4.80, 4.79, 4.76, 4.67 (5 d, 5 H,
PhCH2ꢀ), 4.56 (d, 1 H, J1,2 3.5 Hz, 1-H), 4.37 (s, 2 H,
CH2N3), 4.38–4.32 (m, 2 H, 6a-H, 1 H of PhCH2ꢀ),
4.21 (dd, 1 H, J5,6 5.2, J6,6% 11.9 Hz, 6b-H), 3.96 (dd, 1

90
J. Xu, Z. Guo / Carbohydrate Research 337 (2002) 87–91
129.08, 128.90, 128.09, 127.90, 123.75, 118.93, 114.53
(ArC), 97.52 (1-C), 73.83, 69.52, 55.65, 54.22 (sugar C),
63.22 (6-C), 52.93, 53.71 (2 CH2N3), 38.44, 38.25 (2
PhCH2CO); FABMS: 638 [M+−OMp], 610 [638−
N2], 447 [638−AMPA−H], 419 [447−N2, 100%];
HRFABMS: Calcd for C37H36N5O10 [M+−N2+H],
734.2461. Found, 734.2459.
H, J2,3 9.2, J3,4 9.2 Hz, 3-H), 3.79–3.75 (m, 1 H, 5-H),
3.46 (dd, 1 H, J1,2 3.5 Hz, 2-H), 3.31 (dd, 1 H, 4-H),
3.29 (s, 3 H, OMe); FABMS: 606 [M+−OMe]; 578
[606−N2, 100%]; HRFABMS: Calcd for C37H40NO7
[M+−N2+H], 610.2804. Found, 610.2787.
3-O-(2-Azidomethyl)phenylacetyl-1,2:5,6-di-O-isopro-
pylidene-h- -glucofuranose (13).—0.38 g, 88% yield;
D
colorless syrup; [h]2D5 −62.7° (c 1.7, CHCl3); eluent: 1:4
In addition to the major product 15, the reaction
between 5 and 10 also gave a minor product, p-
1
EtOAc–hexane; H NMR (CDCl3) l: 7.44–7.34 (m, 4
H, AMPA ArH), 5.89 (d, 1 H, J1,2 3.7 Hz, 1-H), 5.21
(bd, 1 H, J3,4 3.0 Hz, 3-H), 4.59 (bd, 1 H, 2-H), 4.53 (s,
2 H, PhCH2N3), 4.19 (dd, 1 H, J4,5 7.5 Hz, 4-H),
4.14–3.83 (m, 3 H, 5-H, 6a-H, 6b-H), 3.91–3.83 (dd, 2
H, J 16.3 Hz, PhCH2CO), 1.45, 1.33, 1.27, 1.26 (4 s, 12
H, 4 CH3); 13C NMR (CDCl3): l 170.65 (CꢁO), 135.55,
134.26, 132.32, 130.75, 129.62, 128.63 (ArC), 106.21
(1-C), 84.18, 80.75, 77.34, 73.40 (sugar C), 67.66 (6-C),
53.23 (CH2N3), 38.77 (PhCH2CO), 27.14, 27.09, 26.50,
25.62 (CH3); FABMS: 243 [M+−AMPA], 118
[C8H8N, 100%]; HRFABMS: Calcd for C20H24NO7
[M+−CH3], 418.1615. Found, 418.1643.
methoxyphenyl
acetyl]-2-deoxy-2-phthalimido-b-
3,4,6-tri-O-[(2-azidomethyl)phenyl-
-glucopyranoside
D
(16).—0.11 g, 12% yield; colorless syrup; 1H NMR
(CDCl3) l 7.80–7.70 (m, 4 H, Phth ArH), 7.35–7.26
(m, 8 H, AMPA ArH), 7.20–6.93 (m, 4 H, AMPA
ArH), 6.82–6.69 (m, 4 H, Mp ArH), 5.83 (dd, 1 H, J2,3
10.9, J3,4 9.2 Hz, 3-H), 5.73 (d, 1 H, J1,2 8.5 Hz, 1-H),
5.12 (dd, 1 H, J4,5 9.3 Hz, 4-H), 4.42 (dd, 1 H, 2-H),
4.37, 4.30 (2 s, 2 H each, 2 CH2N3), 4.19–4.02 (m, 2 H,
6a-H, 6b-H), 4.11 (d, 2 H, J 14.8 Hz, PhCH2N3),
3.88–3.83 (m, 1 H, 5-H), 3.77, 3.58, 3.36 (3 s, 2 H each,
3 PhCH2CO), 3.72 (s, 3 H, OCH3); FABMS: 811
[M+−OMp], 783 [811−N2], 620 [811−AMPA−Hz],
592 [620−N2], 429 [811−2×AMPA−H), 592 [429−
N2], 238 [811−3×AMPA−H], 118 [C8H8N, 100%];
HRFABMS: Calcd for C48H43N8O11 [M+−N2+H],
907.3051. Found, 907.3045.
Methyl
2,3,4-tri-O-acetyl-6-O-[(2-azidomethyl)-
phenylacetyl]-h- -glucopyranoside (14).—0.43 g, 87%
D
yield; white solid; mp 105–107 °C; [h]2D5 +68.8° (c 0.7,
1
CHCl3); eluent: 1:2 EtOAc–hexane; H NMR (CDCl3):
l 7.29–7.26 (m, 4 H, AMPA ArH), 5.43 (dd, 1 H, J4,5
10.0, J3,4 9.6 Hz, 4-H), 4.97 (dd, 1 H, J2,3 10.2 Hz, 3-H),
4.88 (d, 1 H, J1,2 3.6 Hz, 1-H), 4.81 (dd, 1 H, 2-H), 4.40
(s, 2 H, CH2N3), 4.29–4.13 (m, 2 H, 6a-H, 6b-H),
3.97–3.90 (m, 1 H, 5-H), 3.75 (s, 2 H, PhCH2CO), 3.30
(s, 3 H, OMe), 2.05, 1.98 (2 s, 9 H, 3 CH3CO); 13C
NMR (CDCl3): l 170.83, 170.23, 170.20, 169.65 (CꢁO),
134.18, 132.71, 131.42, 129.90, 128.93, 127.97 (ArC),
96.73 (1-C), 70.80, 70.06, 68.51, 67.18 (sugar C), 62.44
(6-C), 55.43 (OCH3), 52.81 (CH2N3), 38.20
(PhCH2CO), 20.78, 20.74, 20.67 (3 CH3CO); FABMS:
462 [M+−OMe], 434 [462−N2], 118 [C8H8N, 100%];
HRFABMS: Calcd for C22H28NO10 [M+−N2+H],
466.1712. Found, 466.1710.
General procedure for selecti6e remo6al of AMPA
from carbohydrates.—A solution of AMPA-protected
sugar 11–14 in MeOH was stirred with Lindlar catalyst
(60% weight) under a hydrogen atmosphere for 3 h.
The solids were then filtered off through filter paper,
and the solutions were concentrated to dryness. The
remains were dissolved in a small amount of CH2Cl2
and applied to silica-gel flash chromatography to give
the deprotected sugars 6–9, respectively, in quantitative
yields (Table 2).
p-Methoxyphenyl 3-O-[(2-azidomethyl)phenylacetyl]-
2-deoxy-2-phthalimido-i- -glucopyranoside (10).—To
D
a mixture of 1:2 trifluoroacetic acid and CH2Cl2 (5 mL)
was added 11 (0.40 g, 0.6 mmol) at 0 °C. After 1 h of
p-Methoxyphenyl
acetyl] - 2 - deoxy - 2 - phthalimido - i -
3,6-di-O-[(2-azidomethyl)phenyl-
- glucopyranoside
D
(15).—0.56 g, 73% yield; colorless syrup; [h]2D5 +3.6° (c
1.4, CHCl3); eluent: 1:4 EtOAc–hexane; 1H NMR
(CDCl3): l 7.81–7.69 (m, 4 H, Phth protons), 7.35–
7.32 (m, 4 H, 6-AMPA ArH), 7.12–7.05 (m, 4 H,
3-AMPA ArH), 6.85–6.70 (m, 4 H, Mp ArH), 5.76 (d,
1 H, J1,2 8.6 Hz, 1-H), 5.68 (dd, 1 H, J2,3 10.8, J3,4 9.0
Hz, 3-H), 4.76 (d, 2 H, J5,6 3.3 Hz, 6a-H, 6b-H), 4.41 (s,
2 H, 6-PhCH2N3), 4.37 (dd, 1 H, 2-H), 4.20, 4.15 (d, 2
H, J 13.8 Hz, 3-PhCH2N3), 3.80 (d, 2 H, J 11.9 Hz,
PhCH2CO), 3.78–3.67 (m, 1 H, 5-H), 3.72 (s, 3 H,
OMe), 3.61 (d, 2 H, J 12.9 Hz, PhCH2COO), 3.58–3.55
(m, 1 H, 4-H), 3.14 (d, 1 H, J 4.4 Hz, 4-OH); 13C NMR
(CDCl3): l 171.47, 155.75, 150.58 (CꢁO), 134,26,
134.09, 133.73, 132.99, 132.31, 131.30, 131.03, 129.91,
Table 2
Removal of AMPA in compounds 11–14 by catalytic hydro-
genation

J. Xu, Z. Guo / Carbohydrate Research 337 (2002) 87–91
91
Calcd for C17H20NO7 [M+−CH3], 378.1302. Found,
378.1295.
stirring at rt, the mixture was diluted with CH2Cl2 (10
mL) and then poured into satd aq NaHCO3 (100 mL).
The organic layer was washed with satd aq NaHCO3
(2×100 mL) and water. The solution was dried over
Na2SO4 and concentrated under vacuum, and the crude
product was purified by flash chromatography (eluent:
1:1 EtOAc–hexane) to afford 10 (0.28 g, 78%) as white
Acknowledgements
This project was supported in part by a Research
Corporation Grant. We thank Jim Faulk for the MS
measurements.
1
solid: mp 50 °C (dec); [h]2D5 +21.3° (c 0.7, CHCl3); H
NMR (CDCl3): l 7.82–7.70 (m, 4 H, Phth ArH),
7.12–7.07 (m, 4 H, AMPA ArH), 6.82–6.69 (m, 4 H,
Mp ArH), 5.84 (d, 1 H, J1,2 8.5 Hz, 1-H), 5.71 (dd, 1 H,
J2,3 10.6, J3,4 8.8 Hz, 3-H), 4.44 (dd, 1 H, 2-H), 4.20 (s,
2 H, PhCH2N3), 3.94–3.71 (m, 4 H, 4-H, 5-H, 6a-H,
6b-H), 3.70 (s, 3 H, OMe), 3.62 (d, 2 H, PhCH2CO),
2.94 (bs, 1 H, OH), 2.03 (bs, 1 H, OH); HRFABMS:
Calcd for C23H21N4O7 [M+−OMp], 465.1411. Found,
465.1402.
References
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Synthesis; Khan, S. H.; O’Neill, R. A., Eds.; Harwood
Academic: New York, 1996; pp. 225–250.
2. Greene, T. W.; Wuts, P. G. M. Protecti6e Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; pp. 17–254.
3. Ziegler, T.; Pantkowski, G. Tetrahedron Lett. 1995, 36,
5727–5730.
4. Ziegler, T.; Pantkowski, G. Liebigs Ann. Chem. 1994,
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5. Watanabe, Y.; Ishimaru, M.; Ozaki, S. Chem. Lett. 1994,
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3-O-[(2-Azidomethyl)phenylacetyl]-1,2-O-isopropyli-
dene-h-
azidomethyl)phenyl acetyl]-1,2:5,6-di-O-isopropylidene-
a- -glucofuranose (13, 0.13 g, 0.3 mmol) in MeOH (4
D
-glucofuranose (18).—A solution of 3-O-[(2-
D
mL) was treated with 0.8% aq H2SO4 (2 mL) at rt for
20 h. At this point, another portion (1 mL) of 0.8% aq
H2SO4 was added, and the mixture was stirred for
another 18 h. After neutralization with sodium bicar-
bonate, MeOH was removed under vacuum, and the
remaining aqueous solution was extracted with CH2Cl2.
The organic layer was washed with water and dried
over Na2SO4. After condensation under vacuum, the
crude product was purified by flash chromatography
(eluent: 1:1 EtOAc–hexane) to afford 18 (94 mg, 80%)
as colorless syrup: [h]2D5 +10.7° (c 0.8, CHCl3); 1H
NMR (CDCl3): l 7.39–7.30 (m, 4 H, AMPA ArH),
5.88 (d, 1 H, J1,2 3.6 Hz, 1-H), 5.28 (bd, 1 H, J3,4 2.6,
3-H), 4.53 (bd, 1 H, 2-H), 4.43, 4.38 (2 d, 1 H each, J
13.8 Hz, PhCH2N3), 4.18 (dd, 1 H, J4,5 9.0 Hz, 4-H),
3.80 (s, 2 H, PhCH2CO), 3.80 (dd, 1 H, J5,6a 3.5, J6a,6b
11.3 Hz, 6a-H), 3.66 (dd, 1 H, 6b-H), 3.57–3.51 (m, 1
H, 5-H), 1.51, 1.31 (2 s, 9 H, 3 CH3); HRFABMS:
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