A divergent method to prepare 5-amino-, 5-N-acetamido-, and 5-N-glycolylsialosides

Article abstract of DOI:10.1002/ejoc.201300664

Sialic acids are essential mediators of biological processes involving carbohydrate recognition. A major determinant of sialic acid recognition is the N-5 substituent, which can be an N-acetyl (human), N-glycolyl (non-human), or amine (cancer associated) functionality. Access to homogeneous sialosides with distinct substitution patterns is essential to determine structure-activity relationships. Herein, we report a divergent chemical approach to enable the synthesis of a library of specifically substituted sialosides by using a single sialic acid building block. A major determinant of sialic acid recognition is the N-5 substituent, which can be an N-acetyl (human), N-glycolyl (non-human), or amine (cancer associated) functionality. Herein, we report a divergent chemical approach to enable the synthesis of the aforementioned 5-N-substituted sialosides by using a single sialic acid building block. Copyright

Full text of DOI:10.1002/ejoc.201300664

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300664
A Divergent Method to Prepare 5-Amino-, 5-N-Acetamido-, and
5-N-Glycolylsialosides
Thomas J. Boltje,*[a] Torben Heise,[a] Floris P. J. T. Rutjes,[a] and Floris L. van Delft[a]
Keywords: Natural products / Carbohydrates / Sialosides / Sialic acids / Glycosylation
Sialic acids are essential mediators of biological processes in-
volving carbohydrate recognition. A major determinant of
sialic acid recognition is the N-5 substituent, which can be an
N-acetyl (human), N-glycolyl (non-human), or amine (cancer
associated) functionality. Access to homogeneous sialosides
with distinct substitution patterns is essential to determine
structure–activity relationships. Herein, we report a diver-
gent chemical approach to enable the synthesis of a library
of specifically substituted sialosides by using a single sialic
acid building block.
A versatile alternative to obtain well-defined glycans is by
chemical synthesis.[8] However, glycosidations with sialic
acid donors are also far from trivial because they are 3-
deoxyketo sugars. This makes the stereochemical outcome
of sialylation difficult to control, and activation of a sialyl
donor may lead to extensive elimination as a result of the
C-1 carboxylic acid(ester) and the sterically hindered nature
of the tertiary oxacarbenium ion.[9] In addition, the protect-
ing group at the N-5 position of the sialic acid can influence
the reactivity and α-selectivity of sialic acid donors,[10]
which has led to the use of a variety of N-5 protecting
groups such as N-diacetyl (Ac2),[11] N-trifluoroacetyl
(TFA),[12] N-2,2,2-trichloroethoxycarbonyl (Troc),[13] 9-
fluorenylmethoxycarbonyl (N-Fmoc),[14] azide (N3),[15] and
N-phthalimide (Phth).[16] A most recent iteration employs
the highly electron-withdrawing 4,5-O,N-oxazolidinone
group to provide excellent α-selectivity.[17] A major draw-
back of the oxazolidinone group, however, is that harsh ba-
sic conditions at high temperature are required for its re-
moval.[17b] Although prior installment of an additional 5-
N-acetyl group allows 5N,4O-oxazolidinone cleavage under
much milder conditions, this procedure is not applicable to
N-glycolylsialosides, as the N-glycolyl moiety, in contrast to
the N-acetyl group, is readily cleaved.[17c,18] On the basis of
the above, it is clear that a robust and versatile method to
prepare 5-N-differentiated sialosides with excellent stereose-
lectivity and reactivity, combined with mild cleavage condi-
tions, is highly desirable.
Introduction
Sialic acids (also known as neuraminic acids) are a di-
verse family of naturally occurring 2-keto-3-deoxynononic
acids that are found on the termini of glycan chains in all
cell types.[1] Sialic acids are involved in a wide range of bio-
logical processes such as fertilization, leukocyte migration,
neuronal plasticity, protein half-life, malignant transforma-
tion, and pathogen recognition and invasion.[1c,2] More
than 50 derivatives of sialic acid are known, including a
human derivative called Neu5Ac. Notably, small differences
in the N-5 substituent differentiates human (Neu5Ac, 5-N-
acetyl), non-human (Neu5Gc, 5-N-hydroxyacetyl), and can-
cer-associated (Neu, 5-amino) sialic acids.[3] Human biosyn-
thesis of Neu5Ac is a consequence of a mutation of the
hydroxylase required for the biosynthesis of Neu5Gc, as a
defense mechanism to prevent pathogen recognition.[4]
However, this difference in sialylation may also lead to ad-
verse effects on human disease.[3a,4,5] For example, trace
amounts of Neu5Gc incorporated in human glycans
through the uptake of dietary Neu5Gc may lead to anti-
Neu5Gc antibodies that are linked to chronic inflammatory
disease and cancer progression.[6] Similarly, therapeutic ap-
proaches that rely on the use of therapeutic cells or glyco-
proteins can be affected by differences in sialylation, as
these products are often contaminated with Neu5Gc.[7]
Hence, homogeneous sialosides with distinct substitution
patterns are essential tools to determine structure–activity
relationships. However, due to the complex sialylation
pattern, it is difficult to obtain pure and well-defined sialos-
ides for biological studies by isolation from natural sources.
Herein, we report such a modular strategy to prepare 5-
N-glycolyl-, 5-N-acetamido-, and 5-aminosialosides by
means of novel 5-N-Boc-protected 5N,4O-oxazolidinone
sialic acid donors 3 and 6 (Figure 1, Ada = adamantyl, Boc
= tert-butoxycarbonyl, Cbz = benzyloxycarbonyl, Bz =
benzoyl). After glycosylation, the oxazolidinone and N-Boc
group can be sequentially cleaved under mild conditions to
afford a 5-amino building block that can be converted into
any type of 5-N-sialoside.
[a] Institute for Molecules and Materials, Radboud University
Nijmegen,
Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands
E-mail: t.boltje@science.ru.nl
Homepage: http://www.ru.nl
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300664.
Eur. J. Org. Chem. 2013, 5257–5261
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5257

T. J. Boltje, T. Heise, F. P. J. T. Rutjes, F. L. van Delft
SHORT COMMUNICATION
Table 1. Stereoselectivity of sialylations with donors 1–6.
Figure 1. N-Acetyl-, N-glycolyl-, and N-Boc-protected sialyl donors
1–6 and glycosyl acceptors 7–9.
Results and Discussion
We started our investigation with the evaluation of the
stability of a 5-N-Boc functionality of 3 and 6 under com-
monly used sialylation conditions, as well as its influence
on the anomeric reactivity and stereoselectivity. For this
purpose, well-established 5-N-acetyl sialyl donor 1[17d] and
5-N-glycolyl donor 2 were prepared for comparison to 5-N-
Boc-protected donor 3. The synthesis of donors 1–3 was
achieved by treating a known sialic acid 4,5-O,N-oxazolidi-
none derivative[17d] with acetyl chloride, benzyloxyacetyl
chloride, and Boc2O, respectively (see the Supporting Infor-
mation). A similar range of phosphate ester sialic acid do-
nors 4–6 was also prepared.[19] In addition, glycosyl ac-
ceptors 7–9 were used to represent common naturally oc-
curring linkages of sialic acid to an underlying glycan,
namely, α-2,6-linkage to galactose or glucosamine and α-
2,3-linkages to galactose, respectively (Figure 1).[19]
Next, we explored the glycosylation behavior of sialyl do-
nors 1–3. Low-temperature (–78 °C) activation with N-
iodosuccinimide (NIS) and trifluoromethanesulfonic acid
(TfOH)[20] in the presence of glycosyl acceptor 7 or 8 in a
mixture of CH2Cl2/acetonitrile (2:1) afforded in all cases
disaccharides 10–15 in high isolated yield with excellent
stereoselectivity (Table 1). Importantly, the 5-N-Boc group
of 3 proved compatible with 0.4 equiv. of TfOH, and there
was no noticeable adverse effect on the α-selectivity. Simi-
larly, phosphate ester donors 4–6 were readily activated at
low temperature (–78 °C) with a stoichiometric amount of
TMSOTf and then treated with glycosyl acceptor 9 to af-
ford α-2,3-sialosides 16–18 in moderate to good yield
(Table 1). The stereoselectivity was excellent for the 5-N-
acetyl (i.e., 4) and 5-N-Boc (i.e., 6) derivatives, but in the
case of 5-N-glycolyl donor 5, a mixture of anomers was
obtained. Again, the 5-N-Boc group proved to be stable at
–78 °C even in the presence of an equimolar amount of
TMSOTf. Taken together, the results in Table 1 show that
the 5-N-Boc group of 3 and 6 is stable under the commonly
used conditions to activate thioglycosides and glycosyl
phosphates, and glycosylation to prepare 2,6- and 2,3-link-
ages proceeds with excellent α-selectivity and high yield.
Next, we investigated the selective removal of the 5N,4O-
[a] Determined by integration of the key signals in the 1H NMR
spectrum. Anomeric configuration was determined by the measure-
3
ment of the characteristic JC1-H3ax coupling constant.[21] [b] Iso-
lated yield.
5258
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5257–5261

A Divergent Method to Prepare 5-N-Substituted Sialosides
oxazolidinone moiety of sialosides 12, 15, and 18. As men- amine functionality, respectively. Notably, the 5-N-Boc
tioned in the Introduction, the 5-N-glycolyl moiety on a group of 18 is orthogonal to commonly used amine protect-
5N,4O-oxazolidinone is not stable under basic conditions ing groups such as the Troc and Cbz groups, which thereby
and is cleaved faster than the 5N,4O-oxazolidinone.[18] In- allows selective functionalization and/or immobilization.
deed, when we treated compound 2 with NaOMe in Thus, the Troc-protected amino group of 15 was converted
MeOH, a mixture of compounds was obtained, and this is into an acetamide by treatment with zinc powder (Ǟ24),
indicative of unselective cleavage. However, the 5-N-Boc followed by conversion into 5-N-acetyl and 5-N-glycolyl de-
group allowed the use of mild conditions to remove the ox- rivatives 25 and 26 by the aforementioned three-step pro-
azolidinone with retention of the carbamate function. The cedure. Hydrogenation led to 28 and 29, which carry an
best results were obtained by treatment of disaccharide 12 aminopentyl spacer that can be used for further immobili-
with NaOMe in a mixture of MeOH and wet THF zation or functionalization. Alternatively, the Cbz-protected
(Scheme 1). MS analysis showed that the Boc carbamate linker can be modified by deacetylation, hydrogenation, and
remained intact, and thus the crude product was treated biotinylation to afford 27 in good overall isolated yield
with CF3CO2H in CH2Cl2 (1:9) for 10 min to afford the (68%). Finally, the 5-N-Boc functionality was deprotected
desired unprotected amine with no observable cleavage of by using 10% CF3CO2H in CH2Cl2 to afford 30 in 99%
the isopropylidene acetal or glycosidic linkage. The crude yield. Deprotected α-sialosides 20, 23, and 28–30 proved to
amine was converted into either 5-N-acetyl sialoside 19 by be stable compounds, as judged by their analysis by NMR
treatment with Ac2O or 5-N-glycolylsialoside 20 by reaction spectroscopy, regardless of the N-5 substitution pattern.
with N-succinimidyl benzyloxyacetate. Disaccharide 18 was Hence, three derivatives (i.e., 28–30) were prepared from a
used to investigate the deprotection of α-2,3-sialosides, single intermediate (i.e., 15), and the overall strategy is suit-
starting with removal of the 4,6-O-benzylidene acetal [cam- able to prepare any type of biologically relevant 5-N deriva-
phorsulfonic acid (CSA), MeOH] to afford diol 21 tive of sialic acid from only one sialic acid building block.
(Scheme 1). Again, the aforementioned three-step reaction
Finally, we investigated the applicability of the above-de-
sequence of deacetylation, 5-N-Boc cleavage, and function- scribed technology to the preparation of fucose-bearing
alization of the crude amine by acetylation or glycolylation tetrasaccharide 39 (Scheme 2). Fucose is often present in
afforded disaccharides 22 and 23 in good overall yields. Fi- sialylated glycan chains and essential for binding to selec-
nally, more challenging disaccharide 15 containing two ad- tins. However, we were aware that, although the glycosidic
ditional amino functions was converted into three different linkages of 12, 21, and 24 were stable during Boc deprotec-
sialosides 28–30 containing a 5-N-acetyl, 5-N-glycolyl, or 5- tion, acidic treatment in the assembly of 39 could well be
Scheme 1. Deprotection to afford 5-amino-, 5-N-acetyl-, and 5-N-glycolylsialosides.
Eur. J. Org. Chem. 2013, 5257–5261
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5259

T. J. Boltje, T. Heise, F. P. J. T. Rutjes, F. L. van Delft
SHORT COMMUNICATION
Scheme 2. Synthesis of N-acetyl- and N-glycolylsialosides in the presence of an acid-labile fucose residue.
problematic with respect to the acid lability of fucosyl link- (Neu5Gc) sialosides as well as sialosides found in cancer
ages. Thus, orthogonally protected disaccharide 33 was pre- cells (Neu), as demonstrated by the selective synthesis of
pared by one-pot reaction of 31 (TBS = tert-butyldimethyl- nine sialosides from only four building blocks. In addition,
silyl) with an aminopentyl linker, followed by glycosylation this method is applicable to the synthesis of complex oligo-
with galactosyl donor 32 by using NIS and TfOH. After saccharides that contain highly acid-labile fucose residues.
Fmoc deprotection (Ǟ34), fucosylation with 35[22] pro-
moted by NIS/TfOH afforded trisaccharide 36 in good yield
with good stereoselectivity (α/β = 10:1). Removal of the all-
yloxycarbonyl (Alloc) group with Pd(PPh3)4 afforded tri-
saccharide acceptor 37 in excellent yield, and finally sialyl-
ation of the primary alcohol with 3 led to desired complex
tetrasaccharide 38 in good yield with excellent stereoselec-
tivity. Deprotection of the Troc carbamate with Zn/AcOH
was followed by desilylation with HF·pyridine. Thus, the
Experimental Section
General Procedures: 1H NMR and 13C NMR spectra were recorded
with a Varian Inova 400 MHz or Bruker Avance III 500 MHz spec-
trometer. Chemical shifts are reported in parts per million (ppm)
relative to tetramethylsilane as the internal standard. NMR spec-
troscopic data is presented as follows: Chemical shift, multiplicity
(s = singlet, br. s = broad singlet, d = doublet, t = triplet, dd =
stage was set for the pivotal deprotection–functionalization
sequence. First, deacetylation with NaOMe/MeOH/THF
readily hydrolyzed acetyl and methyl esters as well as the
oxazolidinone. Next, the resulting intermediate was briefly
treated (10 min) with only 10% CF3CO2H in CH2Cl2 to
obtain the free amine. Much to our satisfaction, MS analy-
sis of the crude reaction mixture showed that the Boc carb-
amate was selectively cleaved and the fucosyl linkage was
unaffected. Acylation of the amine afforded the acetamido
and glycolyl derivatives and final hydrogenation afforded 39
and 40 in good overall yields.
doublet of doublets, m = multiplet and/or multiple resonances),
integration, coupling constant in Hz. All NMR signals were as-
signed on the basis of 1H NMR, 13C NMR, COSY, and HSQC
experiments. Mass spectra were recorded with a JEOL JMS-
T100CS AccuTOF mass spectrometer. Column chromatography
was performed on silica gel, 0.035–0.070 mm, 60 Å, Acros organics
and automatic column Büchi fraction-collector C-660, Büchi
pump-manager C-615, Column-silicycle FLH-R10030B-ISO25 car-
tridge, 4–40 g. TLC analysis was conducted on TLC Silicagel, 60,
F254, Merck, with detection by UV absorption (254 nm) if appli-
cable, and by spraying with 20% sulfuric acid in ethanol followed
by charring at about 150 °C or by spraying with a solution of
(NH4)6Mo7O24·H2O (25 gL–1) in 10% sulfuric acid in ethanol fol-
lowed by charring at about 150 °C. Molecular sieves (3 Å, AW-300)
were flame-activated under vacuum prior to use. All reactions were
carried out under an argon atmosphere.
Conclusions
In conclusion, the method described herein enables the
synthesis of complex 5-N-acetyl-, 5-N-glycolyl-, and 5-
aminosialosides from a single 5-N-Boc sialic acid building
block. The Boc group is stable under commonly used sialyl-
ation conditions, ensures excellent α-selectivity, and affords
α-2,6- and α-2,3-sialosides in high yields. Furthermore, the
Boc group allows mild and selective cleavage of the 5N,4O-
oxazolidinone, and the resulting amine can be function-
General Procedure for Sialylation with Thioglycosides 1–3 (GP1):
Glycosyl acceptor (0.1 mmol) and glycosyl donor (0.15 mmol,
1.5 equiv.) were dissolved in a mixture of dichloromethane (2.0 mL)
and acetonitrile (1.0 mL) and activated molecular sieves were
added. The resulting mixture was stirred for 10 min at room tem-
perature and then cooled to –78 °C, and NIS (0.15 mmol,
1.5 equiv.) was added. TfOH (0.04 mmol, 0.4 equiv.) was added,
and the mixture was stirred for 20 min at –78 °C. Et3N (0.05 mL)
alized to afford human (Neu5Ac) and non-human was added, and the mixture was warmed to room temperature.
5260
www.eurjoc.org
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2013, 5257–5261

A Divergent Method to Prepare 5-N-Substituted Sialosides
3
EtOAc (5 mL) and Na2S2O3 (1 m in H2O, 5 mL) were, added and
the organic layer was separated, dried (MgSO4), and concentrated
in vacuo. The residue was purified by silica gel column chromatog-
raphy.
thanked for his help determining the JC1-H3ax coupling cons-
tants.
[1] a) R. Schauer, Glycoconjugate J. 2000, 17, 485; b) T. Angata,
A. Varki, Chem. Rev. 2002, 102, 439; c) A. Varki, Nature 2007,
446, 1023.
General Procedure for Sialylation with Glycosyl Phosphates 4 and 5
(GP2): Glycosyl acceptor (0.1 mmol) and glycosyl donor
(0.15 mmol, 1.5 equiv.) were dissolved in dichloromethane (2.0 mL)
and activated molecular sieves were added. The resulting mixture
was stirred for 10 min at room temperature and then cooled to
–78 °C, and TMSOTf (0.15 mmol, 1.5 equiv.) was added. The mix-
ture was stirred for 60 min at –78 °C. Et3N (0.05 mL) was added,
and the mixture was warmed to room temperature. EtOAc (5 mL)
and water (5 mL) were added, and the organic layer was separated,
dried (MgSO4), and concentrated in vacuo. The residue was puri-
fied by silica gel column chromatography.
[2] A. Varki, Trends Mol. Med. 2008, 14, 351.
[3] a) A. Varki, Glycoconjugate J. 2009, 26, 231; b) A. Varki,
Trends Mol. Med. 2008, 14, 351; c) I. Popa, A. Pons, C. Mar-
iller, T. Tai, J.-P. Zanetta, L. Thomas, J. Portoukalian, Glycobi-
ology 2007, 17, 367.
[4] a) A. Irie, S. Koyama, Y. Kozutsumi, T. Kawasaki, A. Suzuki,
J. Biol. Chem. 1998, 273, 15866; b) H. H. Chou, H. Takematsu,
S. Diaz, J. Iber, E. Nickerson, K. L. Wright, E. A. Muchmore,
D. L. Nelson, S. T. Warren, A. Varki, Proc. Natl. Acad. Sci.
USA 1998, 95, 11751.
[5] B. Lieberman, Nature 2008, 454, 21.
General Procedure for 4,5-O,N-Oxazolidinone and Boc Cleavage
(GP3): Starting material 12, 21, 24, or 38 (0.1 mmol) was dissolved
in a mixture of wet THF (2 mL) and MeOH (0.5 mL). KOtBu
(0.3 mmol, 3.0 equiv.) was added, and the resulting mixture was
stirred for 16 h at room temperature. Dowex H+ was added, and
the mixture was filtered and concentrated in vacuo. The residue
was dissolved in CH2Cl2 (1.8 mL) and CF3CO2H (0.2 mL) was
added. The mixture was stirred for 10 min at room temperature
and toluene (2 mL) was added. The mixture was concentrated
in vacuo, and the residue was coevaporated with toluene (3ϫ 2 mL)
to afford the crude amine, which was used without further purifica-
tion.
[6] a) A. Zhu, R. Hurst, Xenotransplantation 2002, 9, 376; b) D. H.
Nguyen, P. Tangvoranuntakul, A. Varki, J. Immunol. 2005, 175,
228; c) P. Tangvoranuntakul, P. Gagneux, S. Diaz, M. Bardor,
N. Varki, A. Varki, E. Muchmore, Proc. Natl. Acad. Sci. USA
2003, 100, 12045.
[7] a) M. J. Martin, A. Muotri, F. Gage, A. Varki, Nat. Med. 2005,
11, 228; b) J. Qian, T. Liu, L. Yang, A. Daus, R. Crowley, Q.
Zhou, Anal. Biochem. 2007, 364, 8.
[8] a) X. Zhu, R. R. Schmidt, Angew. Chem. 2009, 121, 1932; An-
gew. Chem. Int. Ed. 2009, 48, 1900; b) T. J. Boltje, T. Buskas,
G. J. Boons, Nat. Chem. 2009, 1, 611.
[9] a) G. J. Boons, A. V. Demchenko, Chem. Rev. 2000, 100, 4539;
b) X. Chen, A. Varki, ACS Chem. Biol. 2010, 5, 163.
[10] C. De Meo, U. Priyadarshani, Carbohydr. Res. 2008, 343, 1540.
[11] a) A. V. Demchenko, G. J. Boons, Chem. Eur. J. 1999, 5, 1278;
b) A. V. Demchenko, G. J. Boons, Tetrahedron Lett. 1998, 39,
3065.
[12] C. C. Lin, K. T. Huang, Org. Lett. 2005, 7, 4169.
[13] a) S. Hanashima, B. Castagner, D. Esposito, T. Nokami, P. H.
Seeberger, Org. Lett. 2007, 9, 1777; b) S. Hanashima, P. H. See-
berger, Chem. Asian J. 2007, 2, 1447.
General Procedure for 5-N-Acetylation (GP4): Crude amine
(0.1 mmol) was dissolved in MeOH (2.0 mL), and the resulting
mixture was cooled to 0 °C. Et3N (1.0 mmol, 10.0 equiv.) and Ac2O
(0.5 mmol, 5.0 equiv.) were added, and the mixture was stirred for
5 h at 0 °C. The mixture was concentrated in vacuo, and the residue
was redissolved in MeOH (2 mL). NaHCO3 (0.05 g) was added,
and after 5 min, the mixture was filtered and concentrated in vacuo.
The residue was purified by RP-C18 HPLC (0–20% CH3CN/H2O).
[14] M. Adachi, H. Tanaka, T. Takahashi, Synlett 2004, 609.
[15] C. S. Yu, K. Niikura, C. C. Lin, C. H. Wong, Angew. Chem.
2001, 113, 2984; Angew. Chem. Int. Ed. 2001, 40, 2900.
[16] K. Tanaka, T. Goi, K. Fukase, Synlett 2005, 2958.
[17] a) M. D. Farris, C. De Meo, Tetrahedron Lett. 2007, 48, 1225;
b) H. Tanaka, Y. Nishiura, T. Takahashi, J. Am. Chem. Soc.
2006, 128, 7124; c) D. Crich, W. Li, J. Org. Chem. 2007, 72,
2387; d) D. Crich, W. Li, J. Org. Chem. 2007, 72, 7794; e) P. K.
Kancharla, C. Navuluri, D. Crich, Angew. Chem. 2012, 124,
11267; Angew. Chem. Int. Ed. 2012, 51, 11105.
General Procedure for 5-N-Glycoylation (GP5): Crude amine
(0.1 mmol) was dissolved in DMF (2.0 mL), and the resulting mix-
ture was cooled to 0 °C. Et3N (1.0 mmol, 10.0 equiv.) and N-suc-
cinimidyl benzyloxyacetate (0.12 mmol, 1.2 equiv.) were added, and
the mixture was stirred for 5 h at 0 °C. The mixture was concen-
trated in vacuo, and the residue was redissolved in MeOH (2 mL).
NaHCO3 (0.05 g) was added, and after 5 min, the mixture was fil-
tered and concentrated in vacuo. The residue was purified by RP-
C18 HPLC (0–20% CH3CN/H2O).
[18] D. Crich, B. Wu, Org. Lett. 2008, 10, 4033.
[19] C.-H. Hsu, K.-C. Chu, Y.-S. Lin, J.-L. Han, Y.-S. Peng, C.-T.
Ren, C.-Y. Wu, C.-H. Wong, Chem. Eur. J. 2010, 16, 1754.
[20] G. H. Veeneman, S. H. van Leeuwen, J. H. van Boom, Tetrahe-
dron Lett. 1990, 31, 1331.
Supporting Information (see footnote on the first page of this arti-
cle): 1H NMR and 13C NMR spectra and experimental procedures
for compounds 2, 3, 5, 6, 8, and 10–40.
[21] S. Prytulla, J. Lauterwein, M. Klessinger, J. Thiem, Carbohydr.
Res. 1991, 215, 345.
[22] H. J. Vermeer, C. M. van Dijk, J. P. Kamerling, J. F. G. Vliegen-
thart, Eur. J. Org. Chem. 2001, 193.
Acknowledgments
This research was supported by the Netherlands Organisation for
Scientific Research (NWO) Rubicon program. Paul Schlebos is
Received: May 6, 2013
Published Online: July 12, 2013
Eur. J. Org. Chem. 2013, 5257–5261
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5261