Glysosylation of nucleophiles on ion-exchange resin: A new synthesis of dibenzyl glycosyl phosphates

Full text of DOI:10.1007/s11172-015-1002-7

Russian Chemical Bulletin, International Edition, Vol. 64, No. 5, pp. 1202—1204, May, 2015
1202
Letters to the Editor
Glysosylation of nucleophiles on ionꢀexchange resin:
a new synthesis of dibenzyl glycosyl phosphates*
L. A. Nazarova, A. M. Shpirt, A. V. Orlova, and L. O. Kononov
N. D. Zelinsky Institute of Organic Chemistry,
47 Lenisnky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 137 6148. Eꢀmail: kononov@ioc.ac.ru
One of fundamental problems in the modern carboꢀ
hydrate chemistry is the development of efficient methods
for the synthesis of oligosaccharides which are fragments
of the oligosaccharide chains of natural glycolipids,
glycoproteins, and polysaccharides of biomedical signifiꢀ
cance.1—8 At the present time, along with the purely
chemical synthesis of oligosaccharides9—11 which is suitꢀ
able in principle for the preparation of variety of strucꢀ
tures, the application of enzymes for the intersaccharide
glysoside bond formation (enzymic and chemical enzyꢀ
mic syntehsis)12—14 is becoming increasingly important.
Glycosyltransferases,12 isolated from the natural sources
or (in recent times, increasingly frequently) obtained by
genetic engineering methods, are most widely used. The
use of glycosyltrasferases implies the availability of the
corresponding activated glysosyl donors, viz., nucleotide
sugars (nucleoside monophosphate sugars or nucleoside
diphosphate sugars),15 which, in turn, can be obtained
from glycosyl phosphates.15,16 Note that glycosyl phosꢀ
phates not only are building blocks for the synthesis of
nucleotide sugars, but are also used as glycosyl donors in
the chemical glycosylation reactions.17 In particular, diꢀ
butyl glycosyl phosphates have been applied with success
for the synthesis of earlier unavailable oligosialic acids18
and are used in automated oligosaccharide synthesizꢀ
ers.19,20 A series of known approaches to the chemical
synthesis of glycosyl phosphates is based on glycosylation
as the key step (for more details, see Refs 15 and 16).
In the present communication, we propose a new apꢀ
proach for the synthesis of glycosyl phosphates based on
the reaction between a glycosyl donor and phosphate anꢀ
ions immobilized on anionꢀexchange resin as counterions.
This approach is based on esterification of orthophosphoric
acid and its derivatives ("phosphoric acids") by alkylation
(glycosylation) of the polymeric salt of a phosphoric acid
salt (phosphate form of ionꢀexchange resin). Formation
of carboxylic esters by alkylation of the carboxylate form
of anionꢀexchange resin is known for a long time.21 The
analogous reaction for the preparation of phosphoric esters
by alkylation (including glycosylation) of the phosphate
forms of anionꢀexchange resin has not been described in
the literature (according to the REAXYS database).
To demonstrate the applicability of this approach in
the synthesis of glycosyl phosphates, we chosed glycosylaꢀ
tion of an Amberlyst Aꢀ26 macroporous anionꢀexchange
resin in the dibenzyl phosphate form using acetobroꢀ
mosugars. The dibenzyl phosphate form of the resin was
* On the occasion of the 100th anniversary of the birth of Acadeꢀ
mician N. K. Kochetkov (1915—2005).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1202—1204, May, 2015.
1066ꢀ5285/15/6405ꢀ1202 © 2015 Springer Science+Business Media, Inc.

New synthesis of dibenzyl glycosyl phosphates
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
1203
Scheme 1
Reagents and conditions: (a) acetobromoglucose,22,23 MeCN; (b) acetobromofucose,25 MeCN; (c) acetobromogalactose,24 MeCN;
and (d) acetobromolactose,26,27 MeCN.
Synthesis of dibenzyl glycosyl phosphates using an Amberlyst
Aꢀ26 ionꢀexchange resin in the dibenzyl phosphate form (general
procedure). A suspension of dried Amberlyst Aꢀ26 ionꢀexchange
resin ((BnO)2P(O)O– form, 8 g of the resin per 1 mmol of the
glycosyl donor) in a solution of glycosyl halide (0.1—0.3 mmol)
in anhydrous CH3CN (20 mL per 1 mmol of the glycosyl donor)
was stirred using a shaker at room temperature (25—30 C).
After complete consumption of the glycosyl donor (24—120 h,
TLC control: AcOEt—toluene, 2 : 1 or AcOEt—petroleum ether,
2 : 1), the reaciton mixture was filtered through a cartridge with
silica gel (PrepSepꢀSi, Fisher); the resin and the cartridge were
washed with AcOEt (100 mL). The filtrate was concentrated
(25 C) and the residue was dried in vacuo to yield pure glycosyl
phosphates 1—4 whose 1H, 13C, and 31P NMR spectra coincidꢀ
ed with literature data (for 1 (see Ref. 32) the reaction time ()
was 96 h and the yield was 95%; for 2 (see Ref. 31)  was 24 h and
the yield was 98%; for 3 (see Ref. 32)  was 96 h and the yield was
92%; for 4 (see Ref. 32)  was 120 h and the yield was 97%).
obtained from the resin in the hydrocarbonate form (preꢀ
pared by treatment of the commercially available Amꢀ
berlyst Aꢀ26 hydroxyl form with aqueous NaHCO3) under
the action of the excess of a solution of dibenzyl phosꢀ
phoric acid (BnO)2P(O)OH in a MeCN—H2O (1 : 1) mixꢀ
ture followed by washing with acetonitrile and vacuum
drying of the resin.
The resulted polymeric phosphateꢀcontaining reagent
underwent reaction with a series of acetobromosugars (deꢀ
rivatives of glucose,22,23 galactose,24 fucose,25 and lacꢀ
tose26,27) in anhydrous acetonitrile (Scheme 1). The reacꢀ
tions proceeded unambiguously to result in the formation
of expected dibenzyl glycosyl phosphates 1—4 which were
isolated in high yields (92—99%) as single diastereomers
with equatorial aglycon (inversion of configuration of the
sugar anomeric center was observed in all cases).
Note exceptionally mild conditions of the reaction and
product isolation excluding anomerization of the kinetiꢀ
cally formed equatorial phosphates which are known28—30
for their tendency to transform into the thermodynamiꢀ
cally more stable axial isomers. Of special notice is virtuꢀ
ally quantitative isolation of the equatorial fucose phosꢀ
phate 2 having ꢀconfiguration25,31 whose preparation
as the single anomer frequently presents difficulties due to
its configurational instability. The method proposed for
the synthesis of glycosyl phosphates supplements well the
known approaches.15,16 Note that this reaction is the first
example of using the ionꢀexchange resin as the source
of nucleophile (glycosyl acceptor) in the glycosylation
reactions.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 15ꢀ03ꢀ06149ꢀa).
References
1. A. Varki, R. D. Cummings, J. D. Esko, H. H. Freeze,
P. Stanley, C. R. Bertozzi, G. W. Hart, M. E. Etzler, Essenꢀ
tials of Glycobiology, 2nd ed., Cold Spring Harbor Laboratory
Press, New York, 2008, 784 pp.
2. G. W. Hart, R. J. Copeland, Cell, 2010, 143, 672.
3. H.ꢀJ. Gabius, S. André, J. JiménezꢀBarbero, A. Romero,
D. Solís, Trends Biochem. Sci., 2011, 36, 298.
4. R. D. Astronomo, D. R. Burton, Nature Rev. Drug Discov.,
2010, 9, 308.

1204
Russ.Chem.Bull., Int.Ed., Vol. 64, No. 5, May, 2015
Nazarova et al.
5. R. Roy, T. C. Shiao, Chimia, 2011, 65, 24.
6. M. C. Galan, D. BenitoꢀAlifonso, G. M. Watt, Org. Biomol.
Chem., 2011, 9, 3598.
C.ꢀH. Wong, C.ꢀY. Wu, Angew. Chem., Int. Ed. Engl., 2011,
50, 9391.
19. P. H. Seeberger, Carbohydr. Res., 2008, 343, 1889.
20. C. H. Hsu, S. C. Hung, C. Y. Wu, C.ꢀH. Wong, Angew.
Chem., Int. Ed. Engl., 2011, 50, 11872.
21. G. Cainelli, F. Manescalchi, Synthesis, 1975, 723.
22. R. U. Lemieux, in Methods in Carbohydrate Chemistry, Eds
R. L. Whistler, M. L. Wolfrom, Academic Press, New York—
London, 1963, Vol. 2, p. 221.
23. X. Nie, G. Wang, J. Org. Chem., 2005, 70, 8687.
24. S. Liu, R. N. Ben, Org. Lett., 2005, 7, 2385.
25. G. Baisch, R. Öhrlein, Bioorg. Med. Chem., 1997, 5, 383, and
references cited therein.
7. L. Cipolla, F. Peri, Mini Rev. Med. Chem., 2011, 11, 39.
8. A. Bernardi, J. JiménezꢀBarbero, A. Casnati, C. De Castro,
T. Darbre, F. Fieschi, J. Finne, H. Funken, K.ꢀE. Jaeger,
M. Lahmann, T. K. Lindhorst, M. Marradi, P. Messner,
A. Molinaro, P. V. Murphy, C. Nativi, S. Oscarson, S. Penadés,
F. Peri, R. J. Pieters, O. Renaudet, J.ꢀL. Reymond, B. Richꢀ
ichi, J. Rojo, F. Sansone, C. Schäffer, W. B. Turnbull,
T. VelascoꢀTorrijos, S. Vidal, S. Vincent, T. Wennekes, H. Zuilꢀ
hof, A. Imberty, Chem. Soc. Rev., 2013, 42, 4709.
9. Handbook of Chemical Glycosylation: Advances in Stereoselecꢀ
tivity and Therapeutic Relevance, Ed. A. V. Demchenko,
WileyꢀVCH, Weinheim, 2008, 501 pp.
26. L. O. Kononov, A. V. Kornilov, A. A. Sherman, E. V. Zyryꢀ
anov, G. V. Zatonskii, A. S. Shashkov, and N. E. Nifant´ev,
Russ. J. Biorg. Chem., 1998, 24, 537 (Engl. Transl.) [Bioorg.
Khim., 1998, 24, 608].
10. J. T. Smoot, A. V. Demchenko, Adv. Carbohydr. Chem. Bioꢀ
chem., 2009, 62, 161.
11. S. Kaeothip, A. V. Demchenko, Carbohydr. Res., 2011,
346, 1371.
12. O. Blixt, N. Razi, in Glycoscience: Chemistry and Chemical
Biology, Eds B. FraserꢀReid, K. Tatsuta, J. Thiem, Springerꢀ
Verlag, Heidelberg, 2nd ed., 2008, p. 1361.
13. S. Muthana, H. Cao, X. Chen, Curr. Opin. Chem. Biol., 2009,
13, 573.
14. A. Homann, J. Seibel, Appl. Microbiol. Biotechnol., 2009,
83, 209.
15. G. K. Wagner, T. Pesnot, R. A. Field, Nat. Prod. Rep., 2009,
26, 1172.
16. N. Oka, K. Sato, T. Wada, Trends Glycosci. Glycotechnol.,
2012, 24, No. 138, 152.
17. 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.
18. K.ꢀC. Chu, C.ꢀT. Ren, C.ꢀP. Lu, C.ꢀH. Hsu, T.ꢀH. Sun,
J.ꢀL. Han, B. Pal, T.ꢀA. Chao, Y.ꢀF. Lin, S.ꢀH. Wu,
27. W. Seebacher, R. Weis, J. Jurenitsch, K. Rauchensteiner,
E. Haslinger, Monatsh. Chem., 2000, 131, 985.
28. V. N. Shibaev, L. L. Danilov, in Studies in Natural Products
Chemistry, Stereoselective synthesis, Ed. AttaꢀurꢀRahman,
Elsevier, Amsterdam, 1991, Vol. 8, Part E, p. 63.
29. P. A. Illarionov, V. I. Torgov, V. N. Shibaev, Russ. Chem.
Bull. (Int. Ed.), 2000, 49, 1895 [Izv. Akad. Nauk, Ser. Khim.,
2000, 1924].
30. A. V. Orlova, A. M. Shpirt, N. Y. Kulikova, L. O. Kononov,
Carbohydr. Res., 2010, 345, 721.
31. R. R. Schmidt, B. Wegmann, K.ꢀH. Jung, Liebigs Ann.
Chem., 1991, 121.
32. R. Roy, F. Tropper, C. GrandꢀMaitre, Can. J. Chem., 1991,
69, 1462.
Recieved March 5, 2015;
in revised form March 23, 2015