pubs.acs.org/joc
jugates is one of the drawbacks in unraveling the importance
Orthogonal Activation of Propargyl and n-Pentenyl
Glycosides and 1,2-Orthoesters
of these glycoconjugates in the cellular context.2 Chemical or
enzymatic synthesis of oligosaccharides either in solution or
on solid phase is a popular method to access sufficient
quantity of glycoconjugates.3 Glycoconjugates are often
present as oligosaccharides coupled to a lipid, protein,
steroid, etc. and the process of oligosaccharide synthesis
breaks down to the systematic addition of sugar residues in
either a convergent or a linear fashion by means of a
glycosylation reaction.4 A glycosylation reaction involves a
glycosyl donor, usually a protected monosaccharide with an
appendage at the anomeric position that can be activated to
become a leaving group, and an aglycon bearing a lone
hydroxyl group. In this context, several glycosyl donors that
were developed over the past century can be classified into
stable (e.g., n-pentenyl-,5a thio-,5b-d vinyl-,5e 2-carboxyben-
zyl-,5f etc.) and unstable (e.g., imidate-,4a,5g halo-,2f,5h-j etc.)
glycosyl donors depending on the shelf life of the actual
glycosyl donor.
Srinivasa Rao Vidadala, Shivaji A. Thadke, and
Srinivas Hotha*
Division of Organic Chemistry, Combi Chem-BioResource
Center, National Chemical Laboratory (CSIR),
Dr. Homi Bhabha Road, PUNE 411 008, India
Received September 9, 2009
Glycosylations with stable glycosyl donors are advanta-
geous as the appendage at the anomeric position of the donor
serves the dual role of a robust protecting group initially and
later becomes a glycosyl donor upon addition of an appro-
priate promoter. The complete oligosaccharide synthesis
often demands the use of more than one glycosyl donor to
accomplish the target molecule.4
Ogawa popularized general orthogonal glycosylation
strategy is an important milestone in the oligosaccharide
synthesis.6a Orthogonal activation requires at least two
glycosyl donors with appendages that can be activated
independently and in the presence of the other thereby
limiting the number of glycosyl donors eligible for this
powerful technique. Earlier work by Ogawa’s group demon-
strated6a the orthogonal activation strategy using thioglyco-
sides and glycosyl fluorides whereas Demchenko et al. have
reported6b semiorthogonal glycosylation strategy exploiting
thioethyl and n-pentenyl glycosides.
An orthogonal activation strategy with propargyl and
n-pentenyl glycosides has been identified. According to
this methodology, n-pentenyl glycosides can be selectively
activated with NIS/TMSOTf in the presence of either
armed or disarmed propargyl O-glycosides. In addition,
we report herein that propargyl 1,2-orthoesters can be
selectively activated with AuBr3 in CH2Cl2 at room
temperature in the presence of n-pentenyl glycosides.
Similarly, pentenyl 1,2-orthoesters can be selectively acti-
vated with NIS/Yb(OTf)3 in the presence of propargyl
glycosides.
Glycoconjugates and oligosaccharides play significant
roles in various extracellular and intracellular molecular
recognition events.1 Insufficient quantities of the glycocon-
We recently reported that propargyl glycosides can be-
come novel and stable glycosyl donors in the presence of a
catalytic amount of AuCl3 at 60 °C in acetonitrile.7a Further-
more, propargyl 1,2-orthoesters were found7b to give 1,2-
trans stereoselective glycosides with AuBr3 in CH2Cl2 at
room temperature and subsequently temperature-controlled
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DOI: 10.1021/jo901837z
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Published on Web 11/03/2009
J. Org. Chem. 2009, 74, 9233–9236 9233
2009 American Chemical Society