Sonochemistry: A Powerful Way of Enhancing the Efficiency of
Carbohydrate Synthesis
Shenglou Deng, Umesh Gangadharmath, and Cheng-Wei Tom Chang*
Department of Chemistry and Biochemistry, Utah State UniVersity,
0300 Old Main Hill, Logan, Utah 84322-0300
ReceiVed February 22, 2006
Using sonication as a means of facilitating organic reactions in carbohydrate chemistry was explored
under the conditions used for traditional organic synthesis. An array of representative reactions, including
hydroxy group manipulation (acylation, protection/deprotection, acyl group migration), thioglycoside
synthesis, azidoglycoside synthesis, 1,3-dipolar cycloaddition and reductive cleavage of benzylidene,
commonly used in the synthesis of carbohydrate derivatives was examined. A series of glycosylation
reactions that employ thioglycosides, glycosyl trichloroacetimidate, glycosyl bromide and glycosyl acetate
as the glycosyl donors was also examined. Our results demonstrate that sonication can significantly shorten
the reaction time, enhance the reactivity of reactant and lead to superior yield and excellent stereoselectivity.
More importantly, a general protocol of glycosylation may finally be developed. Sonication is compatible
to the conditions used for traditional organic synthesis. We believe that sonication can also be applied to
other areas of synthetic processes.
Introduction
glycosyl donors have been reported.6-10 Sophisticated methods,
like chemoenzymatic synthesis,11 one-pot glycosylation,12,13
solid-phase oligosaccharide synthesis,14,15 and iterative glyco-
sylation,16 have been developed for the goal of alleviating the
challenges in oligosaccharide synthesis.
On the other hand, the idea of promoting reactivity by using
traditional synthetic methods, such as raising the reaction
temperature, for less reactive or so-called “disarmed” glycosyl
donors is considered to be less applicable, presumably because
the reactive intermediates, such as oxycarbenium, are thought
to be labile at higher temperature. To conveniently utilize the
knowledge of carbohydrate chemistry in the literature, our group
Owing to the remarkable biological relevance of carbo-
hydrate,1-3 the synthesis of oligosaccharides or carbohydrate
derivatives has long been the goal pursued by researchers from
various areas.4,5 The complexity and diversity of carbohydrates
found in nature, however, makes the synthesis of carbohydrates
a challenging task despite numerous efforts documented in the
literature. One of the reasons is that different carbohydrate
scaffolds often manifest moderate to drastic different reactivity
in various reactions thus resulting in the requirement of
optimizing conditions for each individual carbohydrate scaffold.
The vast number of developed and employed protecting groups
further fuel the complexity in carrying out carbohydrate
synthesis, one such example being glycosylation. Due to the
difference in the reactivity of glycosyl donors as a result of the
employed protecting groups and the intrinsic structure-associated
reactivity, numerous methods designed for activating various
(6) Toshima, K.; Tatsuta, K. Chem. ReV. 1993, 93, 1503-1531.
(7) Nicolaou, K. C.; Mitchell, H. J. Angew. Chem. Int. Ed. 2001, 40,
1576-1624.
(8) Paulsen, H. Angew. Chem. Int. Ed. 1982, 21, 155-173.
(9) Schmidt, R. R. Angew. Chem. Int. Ed. 1986, 25, 212-235.
(10) Demchenko, A. V. Synlett 2003, 9, 1225-1240.
(11) Gijsen, H. J. M.; Qiao, L.; Fitz, W.; Wong, C.-H. Chem. ReV. 1996,
96, 443-474.
* To whom correspondence should be addressed. Fax: 435-797-3390.
(1) Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 99-110.
(2) Dwek, R. A. Chem. ReV. 1996, 96, 683-720.
(3) Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2357-2364.
(4) PreparatiVe Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel
Dekker: New York, 1997.
(12) Zhang, Z.; Ollmann, I. R.; Ye, X.-S.; Wischnat, R.; Baasov, T.;
Wong, C.-H. J. Am. Chem. Soc. 1999, 121, 734-753.
(13) Koeller, K. M.; Wong, C.-H. Chem. ReV. 2000, 100, 4465-4494.
(14) Seeberger, P. H.; Haase, W.-C. Chem. ReV. 2000, 100, 4349-4394.
(15) Plante, O. J.; Palmacci, E. R.; Seeberger, P. H. Science 2001, 291,
1523-1527.
(5) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J. Chem.
ReV. 1996, 96, 1195-1220.
(16) Huang, X.; Huang, L.; Wang, H.; Ye, X.-S. Angew. Chem. Int. Ed.
2004, 43, 5221-5224.
10.1021/jo060374w CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/10/2006
J. Org. Chem. 2006, 71, 5179-5185
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