Synthesis of oligosaccharide mimetics with glycoaminoxy acids

Article abstract of DOI:10.1002/ejoc.200900945

From readily available di-O-isopropylidene-D-glucose, a Dribofuranoid glycoaminoxy acid and its τBu ester have been efficiently prepared as a new family of sugar building blocks by introducing the phthallmido aminoxy group by a Mitsunobu reaction. We found that the τBu ester can be selectively deprotected with 13.7% TFA in CH₂Cl₂ at 0°C in the pres-ence of the 1,2-O-isopropylldene acetal. This selective deprotection has made possible the synthesis of homo-oligomers of glycoaminoxy acids (up to six sugar units) as a novel type of oligosaccharide mimetics,

Full text of DOI:10.1002/ejoc.200900945

FULL PAPER
DOI: 10.1002/ejoc.200900945
Synthesis of Oligosaccharide Mimetics with Glycoaminoxy Acids
Yanchun Gong,[a,b] Hongbin Sun,[b] and Juan Xie*[a]
Keywords: Aminoxy acids / Carbohydrates / Oligosaccharides / Oligomerization / Synthetic methods
From readily available di-O-isopropylidene-
D
-glucose, a
D
-
ence of the 1,2-O-isopropylidene acetal. This selective de-
protection has made possible the synthesis of homo-oligo-
mers of glycoaminoxy acids (up to six sugar units) as a novel
type of oligosaccharide mimetics.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
ribofuranoid glycoaminoxy acid and its tBu ester have been
efficiently prepared as a new family of sugar building blocks
by introducing the phthalimido aminoxy group by a Mitsu-
nobu reaction. We found that the tBu ester can be selectively
deprotected with 13.7% TFA in CH2Cl2 at 0 °C in the pres-
Introduction
Results and Discussion
We chose di-O-isopropylidene--glucose 1 as the starting
material (Scheme 1) because of its ready availability and low
cost. We decided to introduce the aminoxy acid group onto
the 3- and 5-position of the furanose ring, which could al-
low the further functionalization of the anomeric position.
We attempted to introduce the phthalimidoxy group
through a Mitsunobu reaction. However, 1 did not react
with N-hydroxyphthalimide (PhthN-OH) in the presence of
DEAD or DIAD. This might be due to the steric hindrance
of the 3-OH group. Burke and co-workers reported the in-
troduction of the phthalimidoxy group through the mesyl-
ate.[8] We then transformed 1 into the mesylate 3 or the
triflate 4 under the usual conditions. We observed no reac-
Carbohydrates exist in all living systems and play key
roles in a number of biological events, including various
intracellular recognition processes.[1] The rapidly growing
importance of carbohydrates in biological systems and their
potential medical applications incite the synthesis of vari-
ous carbohydrate mimetics.[2] During the last decade, sugar
amino acids have been successfully used as building blocks
in the synthesis of various glycoconjugates and in designing
bioactive molecules for drug discovery.[3] Very recently, we
synthesized pyranoid glycoaminoxy acids as a new class of
sugar building blocks from α-C-allyl glycosides.[4] Due to
the presence of both aminoxy and carboxylic acid func-
tional groups on the sugar ring, these compounds can be
easily used for the synthesis of oxyamide-linked disaccha-
rides and glycosyl amino acid mimetics. Studies on aminoxy
acids have shown that aminoxy peptides can easily form
intramolecular hydrogen bonds to facilitate turns and heli-
cal structures, and a new family of foldamers has been de-
veloped from α-, β- and γ-aminoxy acids.[5] The synthesis
and characterization of a dimer and trimer of -xylofur-
anoid glycoaminoxy acids have also been recently re-
ported.[6] These interesting results encouraged us to prepare
new glycoaminoxy acids as sugar building blocks. In our
continuing program on the development of carbohydrate
mimetics,[7] we report herein the synthesis of -ribofuranoid
glycoaminoxy acids and their homo-oligomers.
tion upon the treatment of
3 with PhthN-OH or
BocNHOH in the presence of DBU. For the triflate 4, we
obtained only the elimination product 5.[9] We tried a sec-
ond approach by introducing a cyano group, which could
be further modified. Once again, the reaction of 4 with
KCN[10] in DMSO or tBu4NCN[11] in CH3CN led to the
elimination product 5.
To avoid the steric hindrance of the 3-position, we con-
verted 1 into the known 6[12] through a Collins oxidation,
Wittig reaction, hydroboration and hydroxylation in 58%
total yield. The Mitsunobu reaction of 6 with PhthN-OH
led successfully to the phthalimidoxy derivative 7, which we
selectively deprotected to 8 in 85% yield. The oxidative
cleavage with NaIO4 gave aldehyde 9, which we oxidized to
the acid 10 in 84% yield. Because hydrazinolysis is neces-
sary to remove the phthalimido protecting group, we pro-
tected the carboxylic acid as the tBu ester to avoid a trans-
acylation reaction.[5] We obtained the tBu ester 11 after es-
terification with tBu trichloroacetimidate. The direct oxi-
dation of 9 with PCC in the presence of tBuOH and Ac2O
led also to ester 11 in 22% yield. Interestingly, when we
reduced the aldehyde group of 9 to the alcohol so as to
[a] PPSM, ENS Cachan, Institut d’Alembert, CNRS, Universud,
61 av. Président Wilson, 94230 Cachan, France
Fax: +33-1-47402454
E-mail: joanne.xie@ens-cachan.fr
[b] Center for Drug Discovery, College of Pharmacy, China Phar-
maceutical University,
24 Tongjiaxiang, Nanjing 210009, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900945.
Eur. J. Org. Chem. 2009, 6027–6033
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Y. Gong, H. Sun, J. Xie
FULL PAPER
coupling with 10 led successfully to trimer 16 in 63% yield.
We could clearly identify the aminoxy peptide NH proton
1
at δ = 9–10.5 ppm in H NMR spectra.
Scheme 2. Synthesis of a homo-oligodimer and -trimer of a fu-
ranoid glycoaminoxy acid.
For the synthesis of oligomers with more than three
sugar units, it is necessary to selectively deprotect the tBu
ester without cleaving the 1,2-O-isopropylidene group. Af-
ter careful examination of the reaction conditions, we found
that treatment of 14 with 13.7% TFA in CH2Cl2 at 0 °C led
to the desired free acid 17 in 77% yield (Scheme 3). The
reaction with TFA/CH2Cl2 (1:1 or 1:2) led mostly to the
fully deprotected product. With less than 10% TFA, the
deprotection rate was relatively slow. The coupling of acid
17 with aminoxy ester 15 in the presence of EDC/HOBt
gave the tetramer 18 in 63% yield. DEPC failed to promote
the formation of 18. The acidic hydrolysis of 18 offered the
acid 19, which was coupled with aminoxy ester 13 or 15,
leading to the corresponding pentamer 20 (40%) or hexa-
mer 21 (25%). The reaction of aminoxy ester 22 with acid
Scheme 1. Synthesis of a furanoid glycoaminoxy acid.
oxidize it directly to the tBu ester,[7d] the phthalimido group 17 led to a lower yield of 21 (13%). Similarly, the trimer 16
was partially reduced to 12, even at –60 °C. The NaBH4 can be deprotected to the corresponding aminoxy ester 23
reduction at room temp. led to the deprotection of the and free acid 24. The EDC-promoted coupling of 23 with
phthalimidoxy group.[13] Fortunately, a subsequent PCC 17 or 24 led to the corresponding pentamer 20 or hexamer
oxidation of 12 offered the desired ester 11 in 55% yield.
21 in 30% or 20% yield, respectively. However, the EDC-
In order to obtain oligomers of furanoid glycoaminoxy or DPPA-promoted coupling of tetramer 19 with 22 failed
acids, we deprotected the aminoxy group of 11 with methyl- to give the desired octamer.
hydrazine (Scheme 2). The tentative chromatographic puri-
We also tried to protect the aminoxy group with the Cbz
fication of 13 led to its partial decomposition. After isola- group, so as to replace the acid-sensitive tBu ester with a
tion, we treated 13 with the acid 10. The dimer 14 was iso- base-sensitive methyl or ethyl ester. The treatment of amin-
lated in 77–81% yield under three different coupling condi- oxy ester 15 with CbzCl led to 25 in only 32% yield
tions: EDC/HOBt, DPPA (diphenylphosphoryl azide)/ (Scheme 4). We note that after hydrogenolysis, the N–O
DIPEA/NaHCO3 and DEPC (diethyl cyanophosphonate)/ bond of the Cbz-aminoxy group was cleaved, leading to the
Et3N; DPPA and DEPC are organophosphorous reagents alcohol 26. This result is in contrast to that observed by Hu
that have been successfully used in the oligomerization of et al.[14] Nevertheless, the aminoxy peptide bond remained
sugar amino acids.[7d,7e] Hydrazinolysis of 14 followed by stable under these conditions.
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Synthesis of Oligosaccharide Mimetics with Glycoaminoxy Acids
Conclusions
From the readily available di-O-isopropylidene--glu-
cose, -ribofuranoid glycoaminoxy acid derivatives have
been successfully prepared as a novel family of sugar build-
ing blocks. Homo-oligomers (dimer to hexamer) have also
been generated as oligosaccharide mimetics. The easy
derivatization of glycoaminoxy acids should allow the de-
sign and synthesis of various carbohydrate-based molecules
and find wide applications like sugar amino acids.
Experimental Section
1
General: H and 13C NMR and DEPT-135 spectra were recorded
with
a Jeol 400 spectrometer in CDCl3 solutions. Column
chromatography was performed with Silica 60 (40–63 µ). Analyti-
cal thin-layer chromatography was performed with aluminum pre-
coated plates of Silica Gel 60F-254 with detection by UV light or
by spraying with 6  H2SO4 and heating at 300 °C for about 2 min
for sugar derivatives. IR spectra were recorded with a Shimadzu
FTIR-8400S spectrometer. Optical rotations were measured by
using a Jasco P-2000 polarimeter. High-resolution mass spectra
(HRMS) were measured by the Service de Spectrométrie de Masse
de l’Université Pierre et Marie Curie-Paris 6.
General Procedure for Hydrazinolysis: To a solution of phthalimid-
oxy compound (1 mmol) in MeOH/CH2Cl2 (1:4, 12 mL), was
added MeNHNH2 (3 mmol). After the mixture was stirred at room
temp. for 6 h, it was concentrated to dryness and directly used for
the next step without further purification.
General Procedure for the Selective Deprotection of the tBu Ester:
To a solution of the tBu ester (1 mmol) in dry CH2Cl2 (19 mL),
was added dropwise TFA/CH2Cl2 (1:1, 7.2 mL) at 0 °C, and the
reaction mixture was stirred for 7 h. EtOAc (10 mL) was added to
the mixture, most of the solvent was evaporated at room temp.,
and the residue was dried under high vacuum (oil pump) until no
acidic smell could be detected. The residue was purified by
chromatography to afford the corresponding free acid as a colorless
syrup.
General Procedure for the Coupling Reaction: To a solution of free
acid (1 mmol) in anhydrous DMF/CH2Cl2 (1:1, 20 mL), was added
HOBt (1.8 equiv.) and EDC (1.8 equiv.) under nitrogen at 0 °C. Af-
ter the mixture had been stirred for 20 min, the aminoxy derivative
(0.5–2 equiv.) in anhydrous CH2Cl2 (10 mL) was added. The reac-
tion mixture was stirred at room temp. overnight. The solution was
diluted with EtOAc (25 mL), washed with aq. HCl (1 ,
2ϫ10 mL), saturated aq. NaHCO3 (2ϫ10 mL) and brine (10 mL),
dried, filtered, concentrated to dryness and then purified by column
chromatography.
Scheme 3. Synthesis of tetramers to hexamers of a furanoid gly-
coaminoxy acid.
3-Deoxy-3-(hydroxymethyl)-1,2:5,6-di-O-isopropylidene-α-D-allofur-
anose (6): To a solution of pyridine (11.3 mL, 140.5 mmol) in
CH2Cl2 (70 mL), was added CrO3 (6.96 g, 69.6 mmol) in one por-
tion.[15] The mixture was stirred at room temp. for 30 min and then
cooled to 0 °C. A solution of di-O-isopropylidene--glucose 1
(4.6 g, 17.6 mmol) in CH2Cl2 (10 mL) was added, followed by
Ac2O (6.87 mL, 72.6 mmol). After the mixture had benn stirred at
room temp. for 1 h, most of the solvent was evaporated. The ad-
dition of toluene/EtOAc (1:1, 100 mL) to the mixture precipitated
most of the chromium compounds. The decanted solution was fil-
tered through a 70–200 mesh silica gel column (9 g) and concen-
trated under reduced pressure. The obtained ketone was dissolved
in anhydrous THF (20 mL) and directly used for the Wittig reac-
Scheme 4. Dimer protection-group modification.
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Y. Gong, H. Sun, J. Xie
FULL PAPER
tion without further purification. To a mixture of methyltri-
phenylphosphonium bromide (16.5 g, 46.1 mmol) in anhydrous
THF (70 mL), was added tBuOK (5.07 g, 45.2 mmol) in anhydrous
THF (20 mL) under nitrogen at 0 °C. The yellow mixture was
warmed to room temp., stirred for 30 min and then heated to reflux
for 2 h. After the mixture was cooled to 0 °C, the solution of ketone
in anhydrous THF was added and the mixture stirred at room
temp. for 2 h. The reaction mixture was poured into water and
extracted with EtOAc (2ϫ50 mL). The combined organic layers
were washed with brine (2ϫ50 mL), dried (MgSO4), filtered and
concentrated to give a yellow crude product, which was purified by
chromatography (petroleum ether/EtOAc, 15:1, 10:1, then 8:1) to
afford the corresponding alkene as a colorless syrup (3.15 g, 70%).
Rf = 0.82 (petroleum ether/EtOAc, 2:1). To the borane/THF com-
plex (1 , 1.37 mL, 1.37 mmol) at 0 °C under nitrogen, was added
the alkene (150 mg, 0.585 mmol) in THF (1.24 mL). The solution
was stirred at room temp. for 2 h. After the mixture was cooled to
0 °C, THF/H2O (1:1, 0.92 mL), aq. NaOH (2 , 1.1 mL) and aq.
H2O2 (30%, 0.92 mL) were added. The mixture was stirred at room
temp. for 2 h and then diluted with H2O (10 mL) and brine (10 mL)
and extracted with EtOAc (2ϫ20 mL). The combined organic lay-
ers were washed with brine (2ϫ20 mL), dried (MgSO4), filtered
and concentrated under reduced pressure to yield 158 mg of crude
product, which was purified by column chromatography (CH2Cl2/
EtOAc, 20:1) to afford 6 as a colorless syrup (131.9 mg, 82.2%).
Rf = 0.35 (petroleum ether/EtOAc, 2:1). 1H NMR (400 MHz,
CDCl3): δ = 1.32 (s, 3 H, Me), 1.37 (s, 3 H, Me), 1.46 (s, 3 H, Me),
1.52 (s, 3 H, Me), 2.09–2.17 (m, 1 H, 3-H), 3.27 (dd, J = 3.2,
10.1 Hz, 1 H, OH), 3.82–3.95 (m, 3 H, 4-H and 3-CH2), 3.95–4.05
(m, 2 H, 5-H and 6-Ha), 4.13–4.20 (m, 1 H, 6-Hb), 4.75 (t, J =
4.4 Hz, 1 H, 2-H), 5.77 (d, J = 3.7 Hz, 1 H, 1-H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 25.2, 26.3, 26.6, 26.8 (CH3), 51.5 (CH),
59.7, 68.1 (CH2), 77.2, 81.8, 82.6, 104.9 (CH), 110.0, 112.4 (C)
ppm.
was diluted with CH2Cl2 (150 mL), washed with H2O (100 mL),
dried (MgSO4), filtered and concentrated to give aldehyde 9 as a
pure colorless syrup (4.1 g, 100 %), which was directly used for
NMR determination and the next step without further purification.
To a solution of 9 (4.1 g, 11.8 mmol) in tBuOH/CH3CN/H2O
(2:2:1, 61.9 mL), was added NaClO2 (6.1 g, 67.4 mmol) and
NaH2PO4 (4.05 g, 33.8 mmol) at 0 °C, and the mixture was warmed
to room temp. and stirred overnight. H2O (200 mL) was then
added, and the mixture was extracted with Et2O (2ϫ100 mL). The
aq. layer was acidified to pH = 1–2 with aq. HCl (4 , 11 mL) and
then extracted with EtOAc (2ϫ200 mL). The combined organic
layers were washed with brine (2ϫ200 mL), dried (MgSO4), fil-
tered and concentrated to give 10 (3.6 g, 84%) as a colorless syrup,
pure enough for the next step. An analytical sample was purified
by column chromatography (CH2Cl2/MeOH/AcOH, 60:1:0.1). Rf
= 0.61 (CH2Cl2/MeOH/AcOH, 6:0.3:0.15). [α]2D3 = +100.6 (c = 0.36,
1
CHCl3). H NMR (400 MHz, CDCl3): δ = 1.33 (s, 3 H, Me), 1.51
(s, 3 H, Me), 2.73–2.80 (m, 1 H, 3-H), 4.35 (d, J = 11.0 Hz, 1 H,
4-H), 4.45 (dd, J = 4.6, 11.0 Hz, 1 H, 3-CHa), 4.67 (t, J = 10.1 Hz,
1 H, 3-CHb), 5.07 (t, J = 3.6 Hz, 1 H, 2-H), 6.01 (d, J = 3.2 Hz, 1
H, 1-H), 7.76–7.84 (m, 4 H, Phth) ppm. 13C NMR (100 MHz,
CDCl3): δ = 26.4, 26.9 (CH3), 47.2 (CH), 74.0 (CH2), 76.2, 80.3,
106.1 (CH), 113.2 (C), 123.8 (CH), 128.9 (C), 134.8 (CH), 163.7
(C), 173.2 (C) ppm. IR (neat): ν = 2987, 2900, 1721 cm–1. HRMS
˜
(ESI): calcd. for C17H17NO8 [M + Na]+ 386.0852; found 386.0846.
Compound 12: To a solution of aldehyde 9 (113 mg, 0.327 mmol) in
EtOH (4.67 mL) and H2O (1.23 mL), was added NaBH4 (13.6 mg,
0.359 mmol) at –60 °C. After the mixture had been stirred for
40 min, H2O (10 mL) was added, and the mixture was extracted
with CH2Cl2 (3ϫ10 mL). The combined organic layers were dried
(MgSO4), filtered, concentrated under reduced pressure to dryness
and purified by column chromatography (CH2Cl2/MeOH, 60:1) to
1
yield the title product (92.6 mg, 81%) as a colorless syrup. The H
NMR spectrum showed a 2:1 mixture of two diastereoisomers. Rf
3-Deoxy-1,2-O-isopropylidene-3-(phthalimidoxymethyl)-α-D-allofur-
= 0.3 (CH2Cl2/MeOH, 20:1). 1H NMR (400 MHz, CDCl3): δ =
anose (8): To a solution of 6 (8.4 g, 30.6 mmol), PhthN-OH (6.15 g, 1.25–1.33 (m, 3 H, Me), 1.45–1.55 (m, 3 H, Me), 2.60–2.70 (m,
37.7 mmol) and PPh3 (13.1 g, 49.9 mmol) in toluene (286 mL) at
0 °C, was added dropwise DIAD (95%, 9.9 g, 46.5 mmol). The re-
sultant red mixture was stirred at room temp. for 5 h. The mixture
was then washed with H2O (3ϫ100 mL) and brine (2ϫ100 mL),
dried (MgSO4), filtered, concentrated and purified by column
chromatography (CH2Cl2/EtOAc, 60:1) to afford 7 (18.1 g) as a yel-
low syrup, containing impurities from DIAD, which would be sepa-
rated completely after the next step. A solution of 7 (18.1 g, crude
0.34 H), 3.70–3.81 (m, 0.68 H), 3.75–4.12 (m, 3 H, 4-H and 5-
CH2), 4.22–4.65 (m, 2 H, 3-CH2), 4.73–4.83 (m, 1 H, 2-H), 5.80–
5.85 (m, 1 H, 1-H), 5.89 (s, 0.68 H), 5.82 (s, 0.34 H), 7.50–7.80 (m,
4 H, Phth) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.3, 26.6
(CH3), 42.7, 43.6 (CH), 61.8, 74.3, 74.6 (CH2), 81.1, 81.5, 81.6,
81.6, 82.9, 83.0, 104.9, 105.0 (CH), 112.1, 112.4 (C), 123.5, 123.7,
123.8 (CH), 128.9, 129.1 (C), 130.1, 130.3, 133.6 (CH), 141.1 (C)
ppm. IR (neat): ν = 3343, 2987, 2922, 1704 cm–1. HRMS (ESI):
˜
product) in 75% AcOH (266 mL) was stirred at 40 °C for 3 h and calcd. for C17H21NO7 [M + Na]+ 374.1216; found 374.1208.
then concentrated and purified by column chromatography
(CH2Cl2/MeOH, 80:1 to 55:1) to afford the title product (9.87 g,
tert-Butyl 3-Deoxy-1,2-O-isopropylidene-3-(phthalimidoxymethyl)-
α-D-ribofuranuronate (11). Method A: To a solution of 10 (800 mg,
85% over two steps) as a colorless syrup. Rf = 0.3 (CH2Cl2/MeOH,
20:1). [α]2D3 = +82.1 (c = 0.95, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.30 (s, 3 H, Me), 1.49 (s, 3 H, Me), 2.35–2.55 (m, 2
H, 3-H and OH), 3.23–3.33 (m, 1 H, OH), 3.68–3.78 (m, 1 H, 6-
Ha), 3.80–3.90 (m, 2 H, 5-H and 6-Hb), 3.98–4.05 (m, 1 H, 4-H),
4.41 (dd, J = 6.4, 10.6 Hz, 1 H, 3-CHa), 4.71 (m, 1 H, 3-CHb), 4.90
(t, J = 4.4 Hz, 1 H, 2-H), 5.82 (d, J = 4.1 Hz, 1 H, 1-H), 7.75–7.90
(m, 4 H, Phth) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.4, 26.7
(CH3); 46.6 (CH), 63.9 (CH2), 73.0 (CH), 75.5 (CH2), 81.3, 81.5,
104.8 (CH), 112.4 (C), 123.8 (CH), 128.8 (C), 134.9 (CH), 163.8
2.2 mmol) in anhydrous CH2Cl2 (8 mL) and cyclohexane (16 mL),
was added tert-butyl 2,2,2-trichloroacetimidate[16] (0.8 mL,
4.47 mmol). After the mixture had been stirred at room temp. over-
night, catalytic BF3·Et2O (31.2 µL, 0.247 mmol) was added, and
the mixture was stirred for 1 h. Solid NaHCO3 (64 mg, 0.79 mmol)
was then added in one portion, and the mixture was stirred for
another 1 h. After the mixture was filtered, saturated aq. NaHCO3
(20 mL) was added, and the mixture was extracted with EtOAc
(50 mL). The organic layer was washed with saturated aq.
NaHCO3 (20 mL) and brine (20 mL), dried (MgSO4), filtered and
concentrated under reduced pressure to dryness. The crude mate-
rial was purified by chromatography (petroleum ether/EtOAc, 9:1,
6:1 then 4:1) to yield the title compound (890.4 mg, 96%) as a
(C) ppm. IR (neat): ν = 2987, 2896, 1788, 1725 cm–1. HRMS (ESI):
˜
calcd. for C18H21NO8 [M + Na]+ 402.1165; found 402.1159.
3-Deoxy-1,2-O-isopropylidene-3-(phthalimidoxymethyl)-α-
anuronic Acid (10): To a solution of 8 (4.48 g, 11.8 mmol) in EtOH
(169 mL) at 0 °C, was added NaIO4 (5.63 g, 26.3 mmol) in H2O +87.1 (c = 0.19, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.30
(45 mL). After the mixture had been stirred at 0 °C for 30 min, it (s, 3 H, Me), 1.46 (s, 9 H, tBu), 1.52 (s, 3 H, Me), 2.62–2.71 (m, 1
D-ribofur-
colorless syrup. Rf = 0.55 (petroleum ether/EtOAc, 2:1). [α]2D3
=
6030
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Synthesis of Oligosaccharide Mimetics with Glycoaminoxy Acids
H, 3-H), 4.21 (d, J = 10.5 Hz, 1 H, 4-H), 4.45 (dd, J = 4.6, 10.5 Hz,
Trimer 16: Prepared by the coupling of 10 (83.1 mg, 0.229 mmol)
1 H, 3-CHa), 4.63 (t, J = 10.5 Hz, 1 H, 3-CHb), 4.98 (t, J = 4.1 Hz, and 15 (115.4 mg, 0.229 mmol), 63% yield, Rf = 0.36 (CH2Cl2/
1 H, 2-H), 5.98 (d, J = 3.7 Hz, 1 H, 1-H), 7.75–7.85 (m, 4 H, Phth) MeOH, 20:1). [α]2D3 = +40.7 (c = 0.86, CHCl3). 1H NMR
ppm. 13C NMR (100 MHz, CDCl3): δ = 26.4, 26.9, 28.0 (CH3), (400 MHz, CDCl3): δ = 1.29 (s, 3 H, Me), 1.31 (s, 6 H, 2ϫMe),
47.1 (CH), 73.9 (CH2), 77.1, 80.1 (CH), 82.8 (C), 106.0 (CH), 112.6 1.44 (s, 9 H, tBu), 1.46 (s, 3 H, Me), 1.48 (s, 6 H, 2ϫMe), 2.40–
(C), 123.7 (CH), 128.9 (C), 134.7 (CH), 163.8, 169.0 (C) ppm. IR
2.70 (m, 3 H, 3ϫ3-H), 4.07 (dd, J = 6.0, 10.1 Hz, 1 H, CH-ON),
4.12–4.32 (m, 6 H, 3ϫCH-ON and 3ϫ4-H), 4.51 (dd, J = 5.0,
11.0 Hz, 1 H, CH-ON), 4.67 (t, J = 11 Hz, 1 H, CH-ON), 4.76 (t,
J = 4.1 Hz, 1 H, 2-H), 4.84 (t, J = 4.2 Hz, 1 H, 2-H), 5.05 (t, J =
4.1 Hz, 1 H, 2-H), 5.85 (d, J = 3.6 Hz, 1 H, 1-H), 5.91 (d, J =
3.7 Hz, 1 H, 1-H), 5.92 (d, J = 3.2 Hz, 1 H, 1-H), 7.73–7.84 (m, 4
H, Phth), 9.37 (s, 1 H, O-NH), 9.42 (s, 1 H, O-NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 26.4, 26.5, 27.0, 28.0 (CH3), 46.6, 47.1,
47.8 (CH), 72.8, 73.3, 74.7 (CH2), 76.8, 77.6, 78.0, 80.2, 80.3, 80.6
(CH), 82.7 (C), 105.9, 106.0 (CH), 112.6, 113.2, 113.2 (C), 123.7
(CH), 128.9 (C), 134.7 (CH), 163.7, 167.6, 169.3 (C) ppm. IR
(neat): ν = 3660, 2991, 2930, 1730 cm–1. HRMS (ESI): calcd. for
˜
C21H25NO8 [M + Na]+ 442.1478; found 442.1472. Method B: To a
solution of 12 (77.6 mg, 0.222 mmol) in CH2Cl2 (3 mL) was added
PCC (98%, 98 mg, 0.444 mmol), Ac2O (0.21 mL, 2.22 mmol) and
tBuOH (0.422 mL, 4.44 mmol). After the mixture had been stirred
overnight, CH2Cl2 was removed under reduced pressure, and the
residue was purified by column chromatography to yield 11 (51 mg,
55%). The oxidation of 9 under similar conditions afforded 11 in
22% yield.
tert-Butyl 3-Aminoxy-3-deoxy-1,2-O-isopropylidene-α-D-ribofuran-
(neat): ν = 2987, 2904, 1735 cm–1. HRMS (ESI): calcd. for
˜
uronate (13): Prepared from 11 (950.4 mg, 2.265 mmol) according
to the general procedure of hydrazinolysis. To obtain an analyti-
cally pure sample, the residue was treated with saturated aq.
Na2CO3 after the evaporation and extracted with EtOAc. The com-
bined organic layers were washed with brine, dried (MgSO4), fil-
tered and concentrated to dryness to afford the pure product as a
colorless oil (100%). [α]2D3 = +46.4 (c = 0.47, CHCl3). 1H NMR
C39H51N3O18 [M + Na]+ 872.3065; found 872.3060.
Acid Dimer 17: Prepared from dimer 14 (287.9 mg, 0.454 mmol)
according to the general procedure of the selective deprotection of
the tBu group. Column chromatography (CH2Cl2/MeOH/AcOH,
100:2:0.25 then 100:2.5:0.25) afforded 17 (77%) as a colorless
syrup. Rf = 0.45 (CH2Cl2/MeOH/AcOH, 6:0.3:0.15). [α]2D3 = +66.7
1
(400 MHz, CDCl3): δ = 1.31 (s, 3 H, Me), 1.47 (s, 9 H, tBu), 1.50 (c = 0.50, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.30 (s, 3 H,
(s, 3 H, Me), 2.57–2.65 (m, 1 H, 3-H), 3.83 (dd, J = 6.4, 10.5 Hz, Me), 1.31 (s, 3 H, Me), 1.47 (s, 3 H, Me), 1.49 (s, 3 H, Me), 2.50–
1 H, 3-CHa), 3.98 (dd, J = 7.8, 10.5 Hz, 1 H, 3-CHb), 4.18 (d, J =
10.6 Hz, 1 H, 4-H), 4.69 (t, J = 4.1 Hz, 1 H, 2-H), 5.45 (br. s, 2 H,
ONH2), 5.93 (d, J = 3.2 Hz, 1 H, 1-H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 26.5, 26.9, 28.0 (CH3), 47.0 (CH), 71.5 (CH2), 78.6
2.70 (m, 2 H, 2ϫ3-H), 4.11 (dd, J = 6.0, 10.1 Hz, 1 H, CH-ON),
4.20–4.30 (m, 3 H, CH-ON and 2ϫ4-H), 4.47 (dd, J = 5.0,
10.5 Hz, 1 H, CH-ONPhth), 4.69 (t, J = 10.5 Hz, 1 H, CH-
ONPhth), 4.81 (t, J = 10.5 Hz, 1 H, 2-H), 5.05 (t, J = 3.6 Hz, 1 H,
(CH), 80.6 (CH), 82.2 (C), 106.1 (CH), 112.5, 169.6 (C) ppm. IR 2-H), 5.92 (d, J = 3.7 Hz, 1 H, 1-H), 5.94 (d, J = 3.6 Hz, 1 H, 1-
(neat): ν = 2986, 2900, 1743 cm–1. HRMS (ESI): calcd. for
H), 7.73–7.84 (m, 4 H, Phth), 9.46 (s, 1 H, O-NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 26.4, 26.5, 26.9 (CH3), 46.5, 47.7 (CH),
73.0, 74.7 (CH2), 76.8, 77.2, 80.3, 80.5, 106.0, 106.1 (CH), 113.1,
113.3 (C), 123.8 (CH), 128.9 (C), 134.8 (CH), 163.9, 168.0, 171.6
˜
C13H23NO6 [M + Na]+ 312.1423; found 312.1418.
Dimer 14: Prepared by the coupling of 10 (822.8 mg, 2.265 mmol)
and 13 (655.3 mg, 2.265 mmol); 81% yield, Rf = 0.47 (CH2Cl2/
MeOH, 20:1). [α]2D3 = +57.3 (c = 0.66, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 1.30 (s, 3 H, Me), 1.32 (s, 3 H, Me), 1.43
(C) ppm. IR (neat): ν = 2987, 2904, 1726 cm–1. HRMS (ESI): calcd.
˜
for C26H30N2O13 [M + Na]+ 601.1646; found 601.1640.
(s, 9 H, tBu), 1.47 (s, 3 H, Me), 1.50 (s, 3 H, Me), 2.50–2.68 (m, 2 Tetramer 18: Prepared by the coupling of 17 (195 mg, 0.337 mmol)
H, 2ϫ3-H), 4.05–4.28 (m, 4 H, CH2-ON and 2ϫ4-H), 4.52 (dd,
J = 5.0, 11.0 Hz, 1 H, CH-ON), 4.70 (t, J = 11.0 Hz, 1 H, CH-
ON), 4.74 (t, J = 4.1 Hz, 1 H, 2-H), 5.09 (t, J = 3.6 Hz, 1 H, 2-H),
5.91 (d, J = 3.2 Hz, 1 H, 1-H), 5.92 (d, J = 3.2 Hz, 1 H, 1-H), 7.73–
7.84 (m, 4 H, Phth), 9.25 (s, 1 H, O-NH) ppm. 13C NMR
(100 MHz, CDCl3): δ = 26.4, 26.5, 26.9, 28.0 (CH3), 46.5, 48.0
(CH), 72.8, 74.7 (CH2), 76.7, 77.9, 80.2, 80.3 (CH), 82.8 (C), 105.9,
and 15 (170 mg, 0.337 mmol), 63% yield, Rf = 0.29 (CH2Cl2/
MeOH, 20:1). [α]2D3 = +20.5 (c = 0.38, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 1.30 (s, 3 H, Me), 1.33 (s, 3 H, Me), 1.34
(s, 6 H, 2ϫMe), 1.48 (s, 3 H, Me), 1.48 (s, 9 H, tBu), 1.49 (s, 3 H,
Me), 1.51 (s, 3 H, Me), 1.52 (s, 3 H, Me), 2.40–2.95 (m, 4 H, 4ϫ3-
H), 3.95 (dd, J = 6.0, 11.4 Hz, 1 H, CH-ON), 3.90–4.40 (m, 9 H,
5ϫCH-ON and 4ϫ4-H), 4.55 (dd, J = 4.6, 10.6 Hz, 1 H, CH-
106.0 (CH), 112.7, 113.2 (C), 123.7 (CH), 128.9 (C), 134.8 (CH), ON), 4.65–4.80 (m, 3 H, CH-ON and 2ϫ2-H), 4.97 (t, J = 4.1 Hz,
163.8, 167.3, 169.2 (C) ppm. IR (neat): ν = 2987, 2900, 1730 cm–1.
1 H, 2-H), 5.10 (t, J = 4.1 Hz, 1 H, 2-H), 5.85 (d, J = 3.7 Hz, 1 H,
1-H), 5.93 (d, J = 3.7 Hz, 1 H, 1-H), 5.96 (d, J = 3.2 Hz, 1 H, 1-
H), 5.97 (d, J = 2.7 Hz, 1 H, 1-H), 7.73–7.84 (m, 4 H, Phth), 9.47
(s, 1 H, O-NH), 9.62 (s, 1 H, O-NH), 9.87 (s, 1 H, O-NH) ppm.
13C NMR (100 MHz, CDCl3): δ = 26.6, 27.0, 28.0 (CH3), 46.3,
46.7, 47.1, 47.3 (CH), 72.7, 72.9, 74.0, 74.5 (CH2), 76.7, 77.3, 78.2,
78.3, 80.3, 80.6, 80.7 (CH), 82.8 (C), 105.7, 106.1, 106.2 (CH),
112.8, 113.0, 113.2, 113.3 (C), 123.7 (CH), 129.0 (C), 134.7 (CH),
˜
HRMS (ESI): calcd. for C30H38N2O13 [M + Na]+ 657.2272; found
657.2266.
Aminoxy Dimer 15: Prepared from dimer 14 (367.9 mg, 0.58 mmol)
according to the general procedure of hydrazinolysis. An analytical
sample was obtained as for 13: 95% yield, colorless oil. [α]2D3
=
+18.4 (c = 0.76, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.32
(s, 3 H, Me), 1.33 (s, 3 H, Me), 1.46 (s, 12 H, tBu and Me), 1.49
(s, 3 H, Me), 2.50–2.65 (m, 2 H, 2ϫ3-H), 4.00–4.30 (m, 6 H,
2ϫCH2O-N and 2ϫ4-H), 4.72 (t, J = 4.1 Hz, 1 H, 2-H), 4.76 (t,
J = 4.1 Hz, 1 H, 2-H), 5.46 (br. s, 2 H, ONH2), 5.85 (d, J = 3.7 Hz,
163.7, 167.6, 168.0, 168.3, 169.4 (C) ppm. IR (neat): ν = 3674,
˜
2987, 2900, 1726, 1691 cm–1. HRMS (ESI): calcd. for C48H64N4O23
[M + Na]+ 1087.3859; found 1087.3854.
1 H, 1-H), 5.93 (d, J = 3.2 Hz, 1 H, 1-H), 9.18 (s, 1 H, O-NH) Acid Tetramer 19: Prepared from tetramer 18 (69.5 mg,
ppm. 13C NMR (100 MHz, CDCl3): δ = 26.5, 26.9, 27.0, 28.0
0.065 mmol) according to the general procedure of the selective
(CH3), 46.5, 47.5 (CH), 71.1, 72.9 (CH2), 77.7, 78.1, 80.3, 80.5
deprotection of the tBu group. Column chromatography (CH2Cl2/
(CH), 82.8 (C), 105.7 (CH), 106.0 (CH), 112.7, 113.1, 167.6, 169.3 MeOH/HOAc, 100:2.5:0.25 to 100:3.5:0.25) afforded the title com-
(C) ppm. IR (neat): ν = 2982, 2900, 1743, 1696 cm–1. HRMS (ESI):
pound in 52% yield. Rf = 0.28 (CH2Cl2/MeOH/AcOH, 6:0.3:0.15).
˜
calcd. for C22H36N2O11 [M + Na]+ 527.2217; found 527.2211.
[α]2D3 = +40.4 (c = 0.16, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
Eur. J. Org. Chem. 2009, 6027–6033
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6031

Y. Gong, H. Sun, J. Xie
FULL PAPER
1.28 (s, 3 H, Me), 1.30 (s, 3 H, Me), 1.32 (s, 6 H, 2ϫMe), 1.46 (s,
3 H, Me), 1.47 (s, 3 H, Me), 1.49 (s, 6 H, 2ϫMe), 1.51 (s, 3 H,
1
+12.1 (c = 0.42, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.30–
1.36 (m, 9 H, 3ϫMe), 1.46 (s, 9 H, 3ϫMe), 1.49 (s, 9 H, tBu),
Me), 2.40–2.90 (m, 4 H, 4ϫ3-H), 3.90–4.40 (m, 10 H, 3ϫCH2- 2.55–2.70 (m, 3 H, 3ϫ3-H), 4.00–4.40 (m, 9 H, 3ϫCH2-ON and
ON and 4ϫ4-H), 4.48 (dd, J = 5.0, 11 Hz, 1 H, CH-ON), 4.68 (t, 3ϫ4-H), 4.71 (t, J = 3.6 Hz, 1 H, 2-H), 4.77 (t, J = 4.1 Hz, 1 H,
J = 10.6 Hz, 1 H, CH-ON), 4.75 (t, J = 4.1 Hz, 1 H, 2-H), 4.82 (s, 2-H), 4.84 (t, J = 4.1 Hz, 1 H, 2-H), 5.49 (br. s, 2 H, ONH2), 5.85
2 H, 2ϫ2-H), 5.05 (t, J = 4.1 Hz, 1 H, 2-H), 5.80 (d, J = 3.7 Hz, (d, J = 3.7 Hz, 1 H, 1-H), 5.88 (d, J = 3.2 Hz, 1 H, 1-H), 5.93 (t,
1 H, 1-H), 5.91 (d, J = 3.9 Hz, 1 H, 1-H), 5.94 (d, J = 2.3 Hz, 1
H, 1-H), 5.95 (d, J = 3.2 Hz, 1 H, 1-H), 7.73–7.84 (m, 4 H, Phth),
J = 3.7 Hz, 1 H, 1-H), 9.41 (s, 1 H, O-NH), 9.54 (s, 1 H, O-NH)
ppm. 13C NMR (100 MHz, CDCl3): δ = 26.5, 26.9, 27.0, 28.0
9.74 (s, 1 H, O-NH), 9.88 (s, 1 H, O-NH), 10.02 (s, 1 H, O-NH) (CH3), 46.6, 47.1, 47.3 (CH), 71.2, 72.8, 73.6 (CH2), 77.7, 77.9,
ppm. 13C NMR (100 MHz, CDCl3): δ = 26.5, 27.0 (CH3), 46.6, 78.0, 80.3, 80.6, 80.7 (CH), 82.8 (C), 105.7, 105.9, 106.0 (CH),
46.5, 46.9, 47.5 (CH), 72.5, 73.2, 73.7, 74.6 (CH2), 76.8, 77.4, 77.9, 112.7, 113.1, 113.2, 167.9, 169.4 (C) ppm. IR (neat): ν = 2978,
˜
78.0, 80.2, 80.4, 80.6, 106.0 (CH), 113.1, 113.3 (C), 123.7 (CH),
129.0 (C), 134.8 (CH), 163.8, 168.2, 168.3, 168.3, 169.4 (C) ppm.
2896, 1691 cm–1. HRMS (ESI): calcd. for C31H49N3O16 [M +
Na]+ 742.3011; found 742.3005.
IR (neat): ν = 2987, 2904, 1734, 1682 cm–1. HRMS (ESI): calcd.
˜
Acid Trimer 24: Prepared from trimer 16 (73 mg, 0.086 mmol) ac-
cording to the general procedure of the selective deprotection of
the tBu group. Column chromatography (CH2Cl2/MeOH/AcOH,
100:2.5:0.25 then 100:3:0.25) afforded the title compound (76%) as
a colorless syrup. Rf = 0.32 (CH2Cl2/MeOH/AcOH, 6:0.3:0.15).
[α]2D3 = +51.6 (c = 0.39, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
for C44H56N4O23 [M + Na]+ 1031.3233; found 1031.3228.
Pentamer 20: Prepared by the coupling of 19 (10 mg, 0.01 mmol)
and 13 (5.73 mg, 0.02 mmol) in 40% yield and by the coupling of
17 (12 mg, 0.021 mmol) and 23 (10 mg, 0.014 mmol) in 30% yield.
Rf = 0.24 (CH2Cl2/MeOH, 20:1). [α]2D3 = +11.7 (c = 0.21, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 1.31 (s, 3 H, Me), 1.32 (s, 3 H, 1.27 (s, 3 H, Me), 1.31 (s, 6 H, 2ϫMe), 1.45 (s, 3 H, Me), 1.48 (s,
Me), 1.34 (s, 6 H, 2ϫMe), 1.35 (s, 3 H, Me), 1.48 (s, 15 H, tBu
6 H, 2ϫMe), 2.50–2.80 (m, 3 H, 3ϫ3-H), 4.01–4.10 (m, 2 H,
and 2ϫMe), 1.51 (s, 3 H, Me), 1.52 (s, 3 H, Me), 2.50–2.90 (m, 5 2ϫCH-ON), 4.20–4.35 (m, 5 H, 2ϫCH-ON and 3ϫ4-H), 4.49
H, 5ϫ3-H), 3.95 (dd, J = 6.9, 10.6 Hz, 1 H, CH-ON), 4.05–4.40
(m, 12 H, 7ϫCH-ON and 5ϫ4-H), 4.55 (dd, J = 4.6, 11.0 Hz, 1
H, CH-ON), 4.70 (t, J = 11.0 Hz, 1 H, CH-ON), 4.78 (dd, J = 5.0,
10.5 Hz, 2 H, 2ϫ2-H), 4.88 (m, 2 H, 2ϫ2-H), 5.09 (t, J = 3.7 Hz,
(dd, J = 5.0, 11.0 Hz, 1 H, CH-ON), 4.68 (t, J = 10.1 Hz, 1 H,
CH-ON), 4.74 (t, J = 3.7 Hz, 1 H, 2-H), 4.86 (s, 1 H, 2-H), 5.03
(t, J = 3.7 Hz, 1 H, 2-H), 5.92 (d, J = 2.8 Hz, 1 H, 1-H), 5.94 (d,
J = 3.2 Hz, 2 H, 2ϫ1-H), 7.70–7.85 (m, 4 H, Phth), 9.80 (s, 1 H,
1 H, 2-H), 5.90 (d, J = 3.2 Hz, 2 H, 2ϫ1-H), 5.95 (d, J = 3.6 Hz, O-NH), 9.97 (s, 1 H, O-NH) ppm. 13C NMR (100 MHz, CDCl3):
1 H, 1-H), 5.96 (d, J = 3.7 Hz, 2 H, 2ϫ1-H), 7.73–7.84 (m, 4 H,
δ = 26.4, 26.5, 26.9 (CH3), 46.6, 46.9, 47.4 (CH), 72.3, 73.6, 74.5
Phth), 9.57 (s, 1 H, O-NH), 9.76 (s, 1 H, O-NH), 9.80 (s, 1 H, O- (CH2), 76.8, 77.0, 78.1, 80.3, 80.4, 80.6, 106.0, 106.1 (CH), 112.9,
NH), 9.91 (s, 1 H, O-NH) ppm. 13C NMR (100 MHz, CDCl3): δ
= 26.5, 26.6, 27.0, 27.06, 27.11, 28.1 (CH3), 46.4, 46.6, 46.8, 46.9,
113.1, 113.3 (C), 123.8 (CH), 128.9 (C), 134.8 (CH), 163.8, 168.0
(C) ppm. IR (neat): ν = 2986, 2900, 1721, 1673 cm–1. HRMS (ESI):
˜
47.5 (CH), 72.8, 72.9, 73.2, 73.9, 74.6 (CH2), 76.8, 77.6, 77.8, 78.1, calcd. for C35H43N3O18 [M + Na]+ 816.2439; found 816.2444.
78.3, 80.3, 80.6, 80.7, 80.8 (CH), 82.9 (C), 105.9, 106.0, 106.08,
Cbz Dimer 25: To a mixture of 15 (60 mg, 0.119 mmol) and
NaHCO3 (60 mg, 0.713 mmol) in THF/H2O (4:1, 2.5 mL), was
106.2 (CH), 112.8, 113.0,113.2 (C), 123.7 (CH), 129.0 (C), 134.7
(CH), 163.8, 167.9, 168.0, 168.5, 169.4 (C) ppm. IR (neat): ν =
˜
added CBzCl (50 µL, 0.357 mmol) at room temp. After the mixture
had been stirred overnight, the solvent was evaporated in vacuo,
and the residue was dissolved in EtOAc (10 mL), washed with satu-
rated aq. NaHCO3 (3ϫ5 mL) and brine (10 mL), dried, filtered,
concentrated to dryness and purified by column chromatography
(petroleum ether/EtOAc, 7:3 then 1:1) to afford 24 mg of 25 as a
colorless syrup. Yield: 31.6%. Rf = 0.41 (CH2Cl2/MeOH, 20:1).
[α]2D3 = +5.48 (c = 0.49, CHCl3). 1H NMR (400 MHz, CDCl3): δ =
1.30 (s, 3 H, Me), 1.31 (s, 3 H, Me), 1.46 (s, 9 H, tBu), 1.48 (s, 3
H, Me), 1.49 (s, 3 H, Me), 2.50–2.65 (m, 2 H, 2ϫ3-H), 4.10–4.32
2978, 2900, 1743, 1683 cm–1. HRMS (ESI): calcd. for C57H77N5O28
[M + Na]+ 1302.4653; found 1302.4647.
Hexamer 21: Prepared by the coupling of 19 (10 mg, 0.01 mmol)
and 15 (10 mg, 0.02 mmol) in 25% yield, by the coupling of 17
(10.9 mg, 0.018 mmol) and 22 (8.8 mg, 0.009 mmol) in 13% yield
and by the coupling of 24 (18.6 mg, 0.023 mmol) and 23 (16.9 mg,
0.023 mmol) in 20% yield. Rf = 0.21 (CH2Cl2/MeOH, 20:1). [α]2D3
= +11.2 (c = 0.17, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.28–
1.38 (m, 18 H, 6ϫMe), 1.48 (s, 15 H, tBu and 2ϫMe), 1.49–1.51
(s, 12 H, 4ϫMe), 2.50–2.90 (m, 6 H, 6ϫ3-H), 3.90–4.40 (m, 16 H, (m, 6 H, 2ϫCH2-ON and 2ϫ4-H), 4.73–4.80 (m, 2 H, 2ϫ2-H),
5ϫCH2-ON and 6ϫ4-H), 4.55 (dd, J = 5.0, 11.0 Hz, 1 H, CH-
ON), 4.70 (t, J = 10.6 Hz, 1 H, CH-ON), 4.74–4.87 (m, 4 H, 4ϫ2-
5.12 (d, J = 11.9 Hz, 1 H, PhCH-), 5.17 (d, J = 12.4 Hz, 1 H,
PhCH-), 5.82 (d, J = 3.7 Hz, 1 H, 1-H), 5.92 (d, J = 3.2 Hz, 1 H,
H), 4.90 (t, J = 3.1 Hz, 1 H, 2-H), 5.07 (t, J = 3.6 Hz, 1 H, 2-H), 1-H), 7.30–7.40 (m, 5 H, Ph), 7.86 (s, 1 H, NH), 9.30 (s, 1 H, O-
5.89–5.97 (m, 6 H, 6ϫ1-H), 7.73–7.84 (m, 4 H, Phth), 9.80 (s, 1
NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.5, 26.9, 28.0
H, O-NH), 9.82 (s, 1 H, O-NH), 9.84 (s, 1 H, O-NH), 10.05 (s, 1
(CH3), 46.5, 47.1 (CH), 67.7, 72.8, 73.2 (CH2), 77.8, 78.1, 80.3, 80.6
H, O-NH), 10.16 (s, 1 H, O-NH) ppm. 13C NMR (100 MHz, (CH), 82.8 (C), 105.7, 106.0 (CH), 112.7, 113.2 (C), 128.4, 128.6,
CDCl3): δ = 26.5, 27.1, 28.1 (CH3), 46.4, 46.6, 46.7, 46.9, 47.5
(CH), 72.7, 72.9, 73.3, 73.4, 73.8, 74.6 (CH2), 76.9, 77.7, 77.9, 78.0,
78.2, 78.3, 80.3, 80.4, 80.7, 80.79, 80.83, 81.0 (CH), 82.9 (C),
105.96, 106.0, 106.1, 106.3 (CH), 112.7, 113.1, 113.2 (C), 123.7
(CH), 129.0 (C), 134.7 (CH), 163.8, 168.1, 168.2, 168.3, 168.5,
128.7 (CH), 135.5, 157.6, 167.7, 169.3 (C) ppm. IR (neat): ν = 3665,
˜
3287, 2983, 2900, 1726 cm–1. HRMS (ESI): calcd. for C30H42N2O13
[M + Na]+ 661.2585; found 661.2579.
Alcohol Dimer 26: Compound 25 (12 mg, 0.0188 mmol) in MeOH
(2 mL) was hydrogenated in the presence of 10% Pd/C (1.2 mg) at
room temp. for 40 min. The mixture was then filtered, and the sol-
vents were evaporated to dryness to afford the pure title compound
(9.1 mg, 100%). Rf = 0.32 (CH2Cl2/MeOH, 20:1). [α]2D3 = –18.3 (c
= 0.21, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.33 (s, 3 H,
Me), 1.34 (s, 3 H, Me), 1.46 (s, 9 H, tBu), 1.51 (s, 3 H, Me), 1.52
(s, 3 H, Me), 2.26–2.35 (m, 1 H, 3Ј-H), 2.60–2.70 (m, 1 H, 3-H),
169.4 (C) ppm. IR (neat): ν = 2987, 2913, 1734, 1687 cm–1. HRMS
˜
(ESI): calcd. for C66H90N6O33 [M + Na]+ 1517.5446; found
1517.5441.
Aminoxy Trimer 23: Prepared from the trimer (16, 195.5 mg,
0.23 mmol) according to the general procedure of hydrazinolysis.
An analytical sample was obtained as for 13: 79% yield, [α]2D3
=
6032
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 6027–6033

Synthesis of Oligosaccharide Mimetics with Glycoaminoxy Acids
G. W. J. Fleet, M. I. Simone, Tetrahedron: Asymmetry 2007, 18,
2001–2010.
3.79 (t, J = 6 Hz, 1 H, OH), 3.99 (t, J = 6.0 Hz, 2 H, CH2O-),
4.10–4.35 (m, 3 H, CH2ON and 4-H), 4.50 (d, J = 10.1 Hz, 1 H,
4Ј-H), 4.74 (t, J = 4.1 Hz, 1 H, 2Ј-H), 4.76 (t, J = 4.1 Hz, 1 H, 2-
H), 5.84 (d, J = 3.6 Hz, 1 H, 1Ј-H), 5.93 (d, J = 3.2 Hz, 1 H, 1-H),
9.34 (s, 1 H, O-NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 26.3,
26.5, 26.9, 28.0 (CH3), 46.5, 50.2 (CH), 59.8, 73.1 (CH2), 78.1, 80.0,
80.3, 81.6 (CH), 82.9 (C), 105.4, 106.0 (CH), 112.7, 113.3, 168.6,
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169.3 (C) ppm. IR (neat): ν = 2987, 2900, 2326, 1734, 1678 cm–1.
˜
HRMS (ESI): calcd. for C22H35NO11 [M + Na]+ 512.2108; found
512.2102.
Supporting Information (see footnote on the first page of this arti-
cle): Synthesis and characterization of 7, 9 and 14 and copies of
1H, 13C and DEPT NMR spectra of all compounds.
Acknowledgments
Y. G. thanks the Ecole Normale Supérieure de Cachan for a Doc-
torate fellowship.
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Received: August 19, 2009
Published Online: October 15, 2009
Eur. J. Org. Chem. 2009, 6027–6033
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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