Rapid Synthesis of l-Idosyl Glycosyl Donors from α-Thioglucosides for the Preparation of Heparin Disaccharides

Article abstract of DOI:10.1002/ejoc.201800425

A new methodology for the synthesis of the most challenging heparin building block has been developed. Orthogonally protected l-idosyl glycosyl donors were prepared by C5 epimerization of the corresponding thioglucosides using the hydroboration/oxidation method followed by a 4,6-acetal formation. The α-anomeric configuration was crucial, and the bulky C4 substituent was advantageous for the high l-ido diastereoselectivity. The 4,6-arylmethylene group proved to be a directing element in glycosylation, whereby stereoselective α-idosylation could be achieved by using idosyl donors without a C-2 participating group.

Full text of DOI:10.1002/ejoc.201800425

A Journal of
Accepted Article
Title: Rapid Synthesis of L-Idosyl Glycosyl Donors from alpha-
Thioglucosides for the Preparation of Heparin Disaccharides
Authors: Mihály Herczeg, Fruzsina Demeter, Tímea Balogh, Viktor
Kelemen, and Anikó Borbás
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800425
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800425
Supported by

10.1002/ejoc.201800425
European Journal of Organic Chemistry
COMMUNICATION
Rapid Synthesis of L-Idosyl Glycosyl Donors from α-
Thioglucosides for the Preparation of Heparin Disaccharides
Mihály Herczeg,[a] Fruzsina Demeter,[a] Tímea Balogh,[a] Viktor Kelemen[a] and Anikó Borbás[a]*
Abstract: A new methodology for the synthesis of the most
challenging heparin building block has been developed.
Orthogonally protected L-idosyl glycosyl donors were prepared by
C5 epimerization of the corresponding thioglucosides using the
hydroboration/oxidation method followed by a 4,6-acetal formation.
The -anomeric configuration was crucial and the bulky C4
substituent was advantageous for the high L-ido diastereoselectivity.
The 4,6-arylmethylene group proved to be a directing element in
glycosylation thereby stereoselective -idosylation could be
achieved by using idosyl donors without a C-2 participating group.
hydroboration/oxidation is a well-elaborated method for C5
isomerisation of -O-glycosides;[6a,b] however, it has not been
applied on thioglycosides, probably due to the sensitivity of
sulfur towards oxidation and non-trivial synthesis of -
thioglycosides. Herein, we present the first application of this
approach for direct synthesis of orthogonally protected
thioidosides and utilization of them in the synthesis of heparin-
related disaccharides.
Although it is known that the α-anomeric configuration of O-
glycosyl 5-enopyranosides is crucial for the high L-ido-selectivity
of hydroboration, initially, we tested the viability of this procedure
on β-thioglucosides which are available more easily than the α-
congeners (Scheme 1).
Heparin and heparan sulfates (H/HS) are highly sulfated linear
glycosaminoglycan (GAG) polysaccharides, consisting of
alternating N-glucosamine and hexuronic acid units, specifically
either D-glucuronic acid or its C5 epimer L-iduronic acid (IdoA).
GAGs interact with a variety of proteins and thereby play
important roles in a diverse set of biological processes including
blood coagulation, cell growth control, inflammation, tumor
metastasis and viral infection.[1] The synthesis of specific GAG
oligosaccharides or their mimetics as biological probes and
potential new therapeutics is an area of great current interest.[2]
One lasting challenge in heparin/HS synthesis is the efficient
preparation of L-idose or IdoA building blocks, as these sugars
are not readily available. Various methods have been explored
for their synthesis,[3] involving epimerization at C5 of D-glucose[4]
or D-glucuronic acid derivatives,[5] isomerisation of unsaturated
sugars,[6] and homologation of tetroses or pentoses.[7] However,
the idose derivatives obtained by these routes are generally not
applicable directly in heparin/HS syntheses and further multistep
transformation is required to turn them to properly functionalized
glycosyl donors.
Recently, Bols and co-workers published a general method for
the preparation of all eight L-hexoses as the thioglycoside
donors, ready for glycosylations.[8] While this method, based on
iridium-catalyzed CH-activation of the corresponding 6-deoxy L-
hexopyranosides, is highly attractive for most rare L-sugars, in
the specific case of L-idose the synthesis of the corresponding 6-
deoxy precursor requires fourteen steps from L-rhamnose,
including epimerizations at C2 and C3,[8b] making the whole
process particularly lengthy and low-yielding.
We envisaged a rapid, cost-friendly and scalable synthesis of
orthogonally protected L-idose thioglycoside donors by
diastereoselective hydroboration of 5-hexenopyranosides
obtained from the corresponding thioglucosides. The
Scheme 1. Synthesis of L-idose starting from β-D-thioglucosides 1 and 5: a)
toluene, PPh3, I2, imidazole, 75 °C, 30 min (2: 80%, 6: 79%); b) DMF, NaH,
0 °C to rt, 24 h (66%); c) THF, BH3·THF, 0 °C,1.5 h; d) 30% H2O2, 2M NaOH,
0 °C to rt, 50 min; e) CH2Cl2, 2,6-lutidine, TBDMSOTf, 0 °C to rt, 2 h (84%); f)
THF, t-BuOK, 0 °C, 30 min (85%); g) THF, TBAF, 0 °C to rt, 2 h (97%).
Iodination of 1[9] followed by dehydrohalogenation of 2 with
sodium hydride gave 6-deoxy-β-D-xylo-hex-5-enopyranoside 3
which was then subjected to hydroboration/oxidation. To our
great satisfaction, the reactions proceeded cleanly and with high
efficacy. The standard oxidation conditions (i.e. H2O2, NaOH)
reported for O-glycosides proved to be well suited for
thioglycosides as oxidation of the anomeric thioacetal
functionality was not observed. As expected, the corresponding
D-glucoside 1 was formed as the major product, nevertheless,
the desired L-ido thioglycoside 4 was also obtained in 32%
isolated yield. Recently, Łopatkiewicz and Mlynarski have
demonstrated that hydroboration stereoselectivity can be
substantially influenced by the C4 protective group.[10] They
have found that small C4-substituents or free 4-OH group are
[a]
Department of Pharmaceutical Chemistry
University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
E-mail: borbas.aniko@pharm.unideb.hu
Homepage: http://pharmchem.unideb.hu/borbas_a.htm
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800425
European Journal of Organic Chemistry
COMMUNICATION
favorable, while bulky C-4 substituents are unfavorable for L-
idose isomer formation. Hence, in the hope of achieving a higher
L-idose ratio, 5-enopyranoside 9 with a free 4-OH group was
prepared starting from diol 5[11] via routine transformations
including selective iodination of the primary position followed by
silylation of 6, dehydrohalogenation of 7 and desilylation of 8.
8:1 ratio. Zemplén deacetylation of 19 followed by iodination and
subsequent chromatographic purification provided the pure α-
anomer of 21 in 71% yield over two steps. Dehydrohalogenation
of 21 with sodium hydride followed by hydroboration and
oxidation of the obtaining 22 provided the desired L-idose 23 in
56% yield along with its sulfoxide derivative 23a (13%) and
glucose isomer 20 (4%). Although sulfoxide 23a, formed by
over-oxidation of 23, can also be used as a glycosyl donor[14] no
benefits were found using phenyl aglycone instead of ethyl.
Although hydroboration/oxidation of
9 proceeded with an
excellent 89% combined yield, the ratio of the L-ido
diastereoisomer, unfortunately, did not increase.We assume that
the excess borane-THF complex reacts with the 4-OH group of 9
forming a borinic ester at position C4 which exhibits a shielding
effect on the bottom face of the pyranose ring upon
hydroboration, similarly to that of the 4-O-NAP group in
compound 3.
Having established that hydroboration/oxidation of -
thioglycosides occurred with high efficacy we studied the
isomerisation of the α-anomers. Ethyl 1-thioglucoside 12 was
prepared with exclusive α-selectivity in 87% yield by
photoinduced hydrothiolation of the peracetylated 2-
hydroxyglycal 11 as previously reported[12] (Scheme 2).
Deacetylation of 12 followed by selective 6-O-tritylation,
benzylation and subsequent detritylation gave 13 which was
transformed to 5-enopyranoside 15 via dehydrohalogenation of
14 with sodium hydride. Hydroboration/oxidation of 15 afforded
the desired L-idose isomer 16 in a good yield of 68% over two
steps. Interestingly, the oxidation reaction was not as clean as in
the case of the β-phenylthio congeners 3 and 9, some polar
degradation products and small amount of apolar by-products
were detected by TLC monitoring of the reaction. The main
components of the apolar by-products, isolated as an
inseparable mixture of compounds, were identified, after
acetylation and a subsequent chromatographic separation, as
13, the D-gluco isomer of the major product, and the 6-deoxy-D-
glucose derivative 16a.
Scheme 3. Synthesis of L-idose via hydroboration-oxidation of phenylthio α-
enoglycopyranoside 22: a) Ac2O, AcOH, H2SO4, 0 °C, 30 min; b) CH2Cl2,
PhSH, BF3·Et2O, 0 °C to rt 2 h (63% over two steps), c) MeOH, NaOMe, rt, 24
h d) THF, imidazole, Ph3P, I2, 75 °C, 30 min (71% over two steps); e) DMF,
NaH, 0 °C to rt, 24 h (72%); f) THF, BH3·THF, 0 °C, 1.5 h; g) 30% H2O2, 2M
NaOH, 0 °C to rt, 50 min.
Next, we we turned our attention to the synthesis of orthogonally
protected idosyl thioglycosides, useful as building blocks in
glycosylation reactions (Scheme 4). Hence, compound 24[15]
bearing the 2-napthylmethyl group at C4 position was prepared
and converted to enopyranoside 26 via sodium hydride
mediated elimination of the 6-iodo derivative 25. The two-step
isomerisation process of 26 resulted in the desired idose
derivative 27 in 68% yield over two steps. Improving the
dehydroiodination of 25 by using potassium tert-butoxide instead
of NaH was unsuccessful, because this reaction led to the
formation of an inseparable 1:2 mixture of 26 and 26a.
Subjecting this mixture to the hydroboration/oxidation process,
26a having an endocyclic double bond remained unchanged.
Scheme 2. Synthetic route to L-idose starting from ethylthio α-D-
glucopyranoside 12: a) Ref. 12, EtSH, DPAP, hν, rt, 3 x 15 min (87%); b)
NaOMe, MeOH, rt, 24 h; c) pyr, TrCl, DMAP, 0 °C to rt, 24 h; d) DMF, NaH,
BnBr, 0 °C to rt, 24 h; e) CH2Cl2, 90% TFA, rt, 30 min (70% over four steps); f)
toluene, PPh3, I2, imidazole,75 °C, 30 min (76%); g) DMF, NaH, 0 °C to rt, 24 h
(78%); h) THF, BH3·THF, 0 °C, 1.5 h; i) H2O2, 2M NaOH, 0 °C to rt, 50 min.
In order to test whether the formation of by-products could be
suppressed by changing the alkylthio aglycone into an aryl one,
the phenylthio glucoside 21 was prepared and subjected to the
isomerisation process (Scheme 3). After partial acetolysis of
17[13] the obtained 18 was reacted with thiophenol in the
presence of Lewis acid resulting in 19 as an α:β mixture in an
Scheme 4. Hydroboration-oxidation of orthogonally protected α-
thioglucosides: a) toluene, PPh3, I2, imidazole, 75 °C, 30 min; b) DMF, NaH,
0 °C to rt, 24 h; c) THF, BH3·THF, 0 °C, 1.5 h; d) 30% H2O2, 2 M NaOH, 0 °C
to rt, 50 min, e) THF, t-BuOK, 0 °C, 30 min (97%, 26a : 26, 2:1).
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800425
European Journal of Organic Chemistry
COMMUNICATION
The iodination and subsequent elimination reaction were also
performed on compound 28[16] bearing 4-O-p-methoxybenzyl
ether as a temporary protecting group. We were pleased to find
that hydroboration/oxidation of the obtaining enopyranoside 30
having the bulky 4-OPMB group gave rise to the desired idose
derivative 31 in an excellent 75% yield.
glycosidation in the gluco- and galactopyranose series.[22]
However, to the best of our knowledge, the directing effect of the
4,6-acetal group has not been exploited for stereoselective 1,2-
trans-α glycosylations in the lack of a C2 participating group.
We investigated if the isomerisation process could be further
improved by applying a 4-OH derivative in the hydroboration
step (Scheme 5). Compound 32[15] was converted to 33 by
reductive cleavage of the 4,6-acetal ring using the Garegg
method.[17] The freed 4-OH group was temporarily protected by
silylation to afford 34 which was transformed to the 6-OH
derivative 35 by oxidative cleavage of the NAP ether using DDQ.
Iodination
followed
by
sodium
hydride
mediated
dehydroiodination of the obtained 36 gave 37 along with its
desilylated derivative 38 in 36% and 14% yields, respectively.
Treatment of 37 with TBAF afforded enopyranoside 38 in 61%
yield. Unfortunately, hydroboration/oxidation of 38 having a free
hydroxyl group at position C4 proceeded with low efficacy
resulting in the desired idose derivative only in a 41% yield.
Scheme 6. Synthesis of heparin-related disaccharides using idosyl donors
obtained from 27: a) pyr, Ac2O, 0 °C to rt, 24 h (81%); b) CH2Cl2, NIS, TfOH, -
50 to +5 °C, 4 h, (51%); c) CH2Cl2, DDQ, rt, 2 h (61%); d) CH2Cl2, NIS, AgOTf,
-10 °C to rt, 3 h (52%).
A similar glycosylation strategy was pursued with the idosyl
thioglycosides 31 and 39 (Scheme 7.) The oxidative cyclization
of 31 gave 45 in 77% yield. Coupling of 45 with 41 also
proceeded with full α-stereoselectivity giving the heparinoid
disaccharide 46 in 51% yield. Finally, diol 39 was
benzylidenated and the obtained 4,6-O-acetal derivative 47 was
coupled with 41 to result in the desired disaccharide 48 with
exclusive α-stereoselectivity.
Scheme 5. Hydroboration-oxidation of 5-enopyranoside 38 with a free 4-OH
group: a) THF, (CH3)3N·BH3, AlCl3, rt, 30 min (64%); b) CH2Cl2, 2,6-lutidine,
TBDMSOTf, 0 °C to rt, 2.5 h (75%); c) CH2Cl2, H2O, DDQ, rt, 30 min (87%); d)
toluene, PPh3, I2, imidazole, 75 °C, 30 min (99%); e) DMF, NaH, rt, 24 h (37:
36%, 38: 14%); f) THF, TBAF, 0 °C to rt, 2 h (61%); g) THF, BH3·THF, 0 °C,
1.5 h, h) 30% H2O2, 2M NaOH, 0 °C to rt, 50 min (41% over two steps).
With the functionalized idosyl thioglycosides 27, 31 and 39 in
hand, stereoselective synthesis of heparinoid disaccharides was
attempted. First, compound 27 was acetylated and the obtaining
40 was reacted with the aminoglycoside acceptor 41[18] (Scheme
6). Unfortunately, the glycosylation occurred with a low α-
stereoselectivity affording an inseparable 2:1 mixture of the α-
and β-linked disaccharide 42 in 51% yield. The moderate yield of
coupling can be explained with the low reactivity of the 4-OH
group of N-acetylglucosamine.[19] To investigate whether a 4,6-
O-acetal had a beneficial effect on the stereochemical outcome
of glycosidation, compound 27 was converted to the
corresponding 4,6-O-(2-naphthyl)methylene derivative 43 by
oxidative ring closure[20] with DDQ (Scheme 6). To our great
delight, reaction of 41 with the donor 43 led to exclusive
formation of disaccharide 44 with the required α-interglycosidic
linkage. It is well-known from the works by Crich and co-workers
that the 4,6-benzylidene acetal of a donor is a control element in
glycosylations permitting stereoselective 1,2-cis-β glycosidic
bond formation in the mannopyranose series[21] and 1,2-cis-α
Scheme 7. α-Selective glycosylations with 4,6-O-acetal-protected
thioidosides: a) CH2Cl2, DDQ, rt, 1.5 h (77%); b) CH2Cl2, NIS, AgOTf, sym-
collidine, -10 °C to rt, 3 h (51%); c) DMF, PhCH(OMe)2, p-TSA, 50 °C, 1 h
(80%); d) CH2Cl2, NIS, AgOTf, -10 °C to rt, 3 h (53%).
In conclusion, a short route to L-idosyl glycosyl donors was
developed from properly functionalized α-thioglucosides. The
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800425
European Journal of Organic Chemistry
COMMUNICATION
Kajtár-Peredy, P. Fügedi, Carbohydr. Res. 2008, 343, 596–606; d) M.
Herczeg, L. Lázár, A. Mándi, A. Borbás, I. Komáromi, A. Lipták, S.
Antus, Carbohydr. Res. 2011, 346, 1827–1836; e) H. Takahashi, Y.
Hitomi, Y. Iwai, S. Ikegami, J. Am. Chem. Soc. 2000, 122, 2995–3000.
Selected ref.: a) T. Chiba, P. Sinaÿ, Carbohydr. Res. 1986, 151, 379–
389; b) W. Ke, D. M. Whitfield, M. Gill, S. Larocque, S.-H. Yu,
Tetrahedron Lett. 2003, 44, 7767–7770; c) S. Salamone, M. Boisbrun,
C. Didierjean, Y. Chapleur, Carbohydr. Res. 2014, 386, 99–105; d) X.
Cao, Q. Lv, D. Li, H. Ye, X. Yan, X. Yang, H. Gan, W. Zhao, L. Jin, P.
Wang, J. Shen, Asian J. Org. Chem. 2015, 4, 899–902.
key steps include C5 epimerization by hydroboration/oxidation of
the corresponding 5-enopyranosides followed by a 4,6-O-acetal
formation of the obtained 6-hydroxy or 4,6-dihydroxy L-idosides.
We demonstrated that the 4,6-arylmethylene group has a
directing effect on the stereochemistry of glycosylation reaction,
which can be exploited in the stereoselective formation of the α-
L-idosidic bond in the lack of a C2 participating group.
[5]
Importantly, idose or iduronic acid donors with
a C-2
participating group have found exclusive application in heparin
syntheses, hitherto. Our results pave the way to designing new,
more diverse protecting group strategies for the synthesis of
H/HS oligosaccharides. Moreover, the obtained thioidosides can
be oxidised into the corresponding L-iduronic acids in a chemo-
and regioselective manner using the TEMPO/BAIB[23] reagent
combination and this oxidative transformation can easily be
performed at an oligosaccharide level as well.[24]
[6]
[7]
Selected ref.: a) L. Rochepeau-Jobron, J.-C. Jacquinet, Carbohydr. Res.
1997, 303, 395–406; b) H. Takahashi, N. Miyama, H. Mitsuzuka, S.
Ikegami, Synthesis 2004, 18, 2991-2994; c) H. G. Bazin, M. W. Wolff, R.
J. Linhardt, J. Org. Chem. 1999, 64, 144–152.
Selected ref.: a) M. S. M. Timmer, A. Adibekian, P. H. Seeberger,
Angew. Chem. Int. Ed. 2005, 44, 7605–7607; b) A. Adibekian, P.
Bindschädler, M. S. M. Timmer, C. Noti, N. Schützenmeister, P. H.
Seeberger, Chem. Eur. J. 2007, 13, 4510–4522; c) S. U. Hansen, M.
Barath, B. A. B. Salameh, R. G. Pritchard, W. T. Stimpson, J. M.
Gardiner, G. C. Jayson, Org. Lett. 2009, 11, 4528–4531; d) A. Dondoni,
A. Marra, A. Massi, J. Org. Chem. 1997, 62, 6261–6267; e) A.
Lubineau, O. Gavard, J. Alais, D. Bonnaffé, Tetrahedron Lett. 2000, 41,
307–311.
The optimization of our epimerization and glycosylation
procedures and their application in the synthesis of heparin
oligosaccharides are in progress.
[8]
[9]
a) T. G. Frihed, C. M. Pedersen, M. Bols, Angew. Chem. Int. Ed. 2014,
53, 13889–13893; b) T. G: Frihed, C. M. Pedersen, M. Bols, Eur. J. Org.
Chem. 2014, 7924–7939.
Acknowledgements
M. Herczeg, L. Lázár, M. Ohlin, A. Borbás, Carbohydrate Chemistry:
Proven Synthetic Methods, G. van der Marel, J. Codée, Eds.; CRC
Press, 2014, Vol. 2, pp 9-20.
The authors gratefully acknowledge financial support for this
research from the Mizutani Foundation for Glycoscience
(150091), from the National Research, Development and
Innovation Office of Hungary (PD 115645) and from the János
Bolyai Research Scholarship of the Hungarian Academy of
Sciences (M. Herczeg). The research was also supported by the
EU and co-financed by the European Regional Development
Fund under the project GINOP-2.3.2-15-2016-00008.
[10] G. Łopatkiewicz, J. Mlynarski, J. Org. Chem. 2016, 81, 7545–7556.
[11] M. Trumtel, P. Tavecchia, A. Veyrieres, P. Sinay, Carbohydr. Res. 1990,
202, 257–275.
[12] L. Lázár, M. Csávás, M. Herczeg, P. Herczegh, A. Borbás, Org. Lett.
2012, 14, 4650−4653.
[13] R. Eby, S. J. Sondheimer, C. Schuerch, Carbohydr. Res. 1979, 73,
273–276.
[14] D. Kahne, D. Walker, Y. Chen, D. V. Engen, J. Am. Chem. Soc. 1989,
111, 6881–6882.
Keywords: thioglycosides • L-idose • glycosylation •
stereoselective • heparin
[15] M. Herczeg, E. Mező, D. Eszenyi, L. Lázár, M. Csávás, I. Bereczki, S.
Antus, A. Borbás, Eur. J. Org. Chem. 2013, 25, 5570–5573.
[16] E. Mező, M. Herczeg, D. Eszenyi, A. Borbás, Carbohydr. Res. 2014,
388, 19–29.
[1]
[2]
a) B. Casu, U. Lindahl, Adv. Carbohydr. Chem. Biochem. 2001, 57,
159–206; b) N. S. Gandhi, R. L. Mancera, Chem. Biol. Drug Des. 2008,
72, 455–482.
[17] a) M. Ek, P. J. Garegg, H. Hultberg, S. Oscarson, J. Carbohydr. Chem.
1983, 2, 305–311; b) A. Borbás, Z. B. Szabó, L. Jánossy. L. Szilágyi, A.
Bényei, A. Lipták, Tetrahedron, 2002, 58, 5723–5732.
[18] S. S. Rana, J. J. Barlow, K. L. Matta, Carbohydr. Res. 1983, 113, 257-
271.
Selected ref.: a) M. Herczeg, L. Lázár, Z. Bereczky, K. E. Kövér, I.
Timári, J. Kappelmayer, A. Lipták, S. Antus, A. Borbás, A. Chem. Eur. J.
2012, 18, 10643 –10652; b) S. U. Hansen, G. J. Miller, G. C. Jayson, J.
M. Gardiner, Org Lett. 2013, 15, 88–91. c) C.-H. Chang, L. S. Lico, T.-Y.
Huang, S.-Y. Lin, C.-L. Chang, S. D. Arco, S.-C. Hung, Angew. Chem.
Int. Ed. 2014, 53, 9876–9879; d) P. C. Tyler, S. E. Guimond, J. E.
Turnbull, O. V. Zubkova, Angew. Chem. Int. Ed. 2015, 54, 2718–2723;
e) M. Baráth, S. U. Hansen, C. E. Dalton, G. C. Jayson, G. J. Miller, J.
M. Gardiner, Molecules, 2015; 20, 6167–6180; f) E. Mező, D. Eszenyi,
E. Varga, M. Herczeg, A. Borbás, Molecules 2016, 21, 1497; g) N. V.
Sankaranarayanan, R. Tamara, T. R. Strebel, R. S. Boothello, K.
Sheerin, A. Raghuraman, F. Sallas, P. D. Mosier, N. D. Watermeyer, S.
Oscarson, U. R. Desai, Angew. Chem. Int. Ed. 2017, 56, 2312–2317; h)
C. Zong, A. Venot, X. Li, W. Lu, W. Xiao, J.-S. L. Wilkes, C. L. Salanga,
T. M. Handel, L. Wang, M. A. Wolfert, G. J. Boons, J. Am. Chem. Soc.
2017, 139, 9534-9543; i) G. Łopatkiewicz, S. Buda, J. Mlynarski, J. Org.
Chem. 2017, 82, 12701–12714.
[19] a) D. Crich, V. Dudkin, J. Am. Chem. Soc. 2001, 123, 6819-6825; b) L.
Liao, F.-I. Auzanneau, Org. Lett. 2003, 5, 2607-2610.
[20] a) Y. Oikawa, T. Yoshioka, O. Yonemitsu, Tetrahedron Lett. 1982, 23,
889-892; b) H. Kim, H. M. R. Hoffmann, Eur. J. Org. Chem. 2000, 2195-
2201.
[21] a) D. Crich, S. Sun, J. Org. Chem. 1996, 61, 4506–4507; b) D. Crich, S.
Sun, J. Org. Chem. 1997, 62, 1198–1199.
[22] a) D. Crich, W. Cai, J. Org. Chem. 1999, 64, 4926–4930; b) H. N. Yu, J
Furukawa, T. Ikeda, C.-H. Wong, Org. Lett. 2004, 6, 723-726; c) A.
Vibert, C. Lopin-Bon, J.-C. Jacquinet, Chem. Eur. J. 2009, 15, 9561-
9578; d) M. Moumé-Pymbock, T. Furukawa, S. Mondal, D. Crich, J. Am.
Chem. Soc. 2013, 135, 14249–14255.
[23] L. J. van den Bos, J. D. C. Codée, J. C. van der Toorn, T. J. Boltje, J. H.
van Boom, H. S. Overkleeft, G. A. van der Marel, Org. Lett. 2004, 6,
2165–2168.
[3]
[4]
a) F. Vito, Adv. Carbohydr. Chem. Biochem. 2015; 57,159–206; b) T. G.
Frihed, M. Bols, C. M. Pedersen, Chem. Rev. 2015, 115, 3615-3676.
Selected ref.: a) J. C. Jacquinet, M. Petitou, P. Duchaussoy, I.
Lederman, J. Choay, G. Torri, P. Sinaÿ, Carbohydr. Res. 1984, 130,
221–241; b) J.-C. Lee, X.-A. Lu, S. S. Kulkarni, Y.-S. Wen, S.-C. Hung,
J. Am. Chem. Soc. 2004, 126, 476–477; c) J. Tatai, G. Osztrovszky, M.
[24] a) J. D. C. Codée, A. E. Christina, M. T. C. Walvoort, H. S. Overkleeft,
G. A. van der Marel, Top. Curr. Chem. 2011, 301, 253–289; b) M.
Herczeg, E. Mező, D. Eszenyi, S. Antus, A. Borbás, Tetrahedron 2014,
70, 2919-2927.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800425
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Text for Table of Contents
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here))
Layout 2:
COMMUNICATION
Mihály Herczeg, Fruzsina Demeter,
Tímea Balogh, Viktor Kelemen and
Anikó Borbás*
Page No. – Page No.
Rapid Synthesis of L-Idosyl Glycosyl
Donors from α-Thioglucosides for the
Preparation of Heparin Disaccharides
Synthesis of L-idopyranosyl glycosyl donors starting from α- and β-thio-D-
glucopyranosides via the corresponding 5-enopyranosides were studied for the first
time. Hydroboration of the α-configured 5-enopyranosides proceeded with very high
L-ido stereoselectivity. After a 4,6-O-acetal formation, the obtained idosyl
thioglycosides proved to be useful as donors in the synthesis of heparin-related
disaccharides.
This article is protected by copyright. All rights reserved.