been extensively studied. These methods usually have the
drawbacks of reduced reactivity, incapability of removing
anchored unreacted intermediates and byproducts, and difficulty
of structure characterization.
Synthesis and Applications of a Light-Fluorous
Glycosyl Donor
Fa Zhang,† Wei Zhang,‡ Yan Zhang,† Dennis P. Curran,§
and Gang Liu*,†
Fluorous chemistry has been widely used in biphasic catalysis,
combinatorial and parallel synthesis of small molecules, and
separation of biomolecules.5 Since the Curran group first
reported the utility of heavy-fluorous tagged glucal for the
synthesis of a disaccharide,6n more heavy-fluorous tags6 and
new light-fluorous tags7 have been developed for oligosaccharide
synthesis. Most of these reports focused on fluorous-tagged
glycosyl acceptors for the synthesis of oligosaccharides. Tagged
glycosyl donors could have broader applications than acceptor
for the synthesis of oligosaccharides as well as other glyco-
conjugates, but to date the effort on fluorous glycosyl donors is
limited to heavy-fluorous tag.6n The synthesis and separation
for heavy-fluorous tagged compounds rely on highly fluorinated
solvents, which are expensive and persistent. Very recently,
Pohl’s group reported the use of a light-fluorous glycosyl donor
in the synthesis of a monosaccharide.7c We herein introduce
the synthesis of oligosaccharides and glycosylated amino acid
by using a light-fluorous glycosyl donor and an orthogonal
tagging strategy.
Institute of Materia Medica, Chinese Academy of Medical
Sciences and Peking Union Medical College,
Beijing 100050, P. R. China, Department of Chemistry,
UniVersity of Massachusetts-Boston, Boston, Massachusetts
02125, and Department of Chemistry, UniVersity of
Pittsburgh, Pittsburgh, PennsylVania 15260
ReceiVed January 15, 2009
In our current work, a glycosyl donor is attached to a fluorous
tag, and the tagged donor is reacted with a nonfluorous glycosyl
acceptor. The acceptor is used in excess amount to consume
the fluorous donor (Scheme 1). After each glycosylation, the
desired fluorous product is easily isolated by fluorous solid-
A new method using a light-fluorous glycosyl donor and an
orthogonal tagging strategy to synthesize oligosaccharides
and glycoconjugates has been developed. The glycosyl donor
orthogonally protected with a C8F17-silyl tag and benzoyl
groups was reacted with excess amounts of glycosyl acceptor.
Fluorous solid-phase extraction separated the glycosylated
product and unreacted glycosyl acceptor. This new protocol
has high reaction efficiency and easy separation, which was
demonstrated in the synthesis of an unprotected trisaccharide
and an O-glycosylated serine in this paper.
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T.; Tsujino, S.; Satoh, A.; Goto, K.; Mizuno, M.; Noguchi, M.; Kajimoto, T.;
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Carbohydrates play a pivotal role in many biological pro-
cesses, such as cell adhesion, inflammation, immune response,
and tumor metastasis.1 Low glycosylation efficiency and dif-
ficulty of product purification are two major issues in glyco-
chemistry. Numerous chemical and enzymatic glycosylation
methods have been developed.2 However, the separation of
oligosaccharides from deletion sequences still heavily relies on
chromatographic methods. In recent years, synthesis of oli-
gosaccharides on solid support3 or soluble support (PEG)4 has
† Institute of Materia Medica.
‡ University of Massachusetts-Boston.
§ University of Pittsburgh.
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2594 J. Org. Chem. 2009, 74, 2594–2597
10.1021/jo9000993 CCC: $40.75 2009 American Chemical Society
Published on Web 02/13/2009