Here,
we demonstrate that substitution of the benzyl groups of
glucosyl imidate donors with trifluoromethyl results in a substantial
increase in 1,2-
cis
-selectivity when activated with
TMS-I in the presence of triphenylphosphine oxide. Stereoselectivity
is dependent on the number of trifluoromethyl groups (4-trifluoromethylbenzyl
vs 3,5-
bis
-trifluoromethylbenzyl). Particularly encouraging
is that we observe high 1,2-
cis
-selectivity with
reactive alcohol acceptors.
Chemical synthetic
efforts have resulted in the preparation of
the assigned tetrasaccharide repeating subunit from the
Acinetobacter
baumannii
KL4-associated capsular polysaccharide. A convergent
synthetic strategy hinging on a 1,2-
cis
-selective
[2+2] glycosylation to generate the fully protected tetrasaccharide
was key to the success of this synthesis.
Acinetobacter baumannii is a Gram-negative bacteria associated with drug resistance and infection in healthcare settings. An understanding of both the biological roles and antigenicity of surface molecules of this organism may provide an important step in the prevention and treatment of infection through vaccination or the development of monoclonal antibodies. With this in mind, we have performed the multistep synthesis of a conjugation-ready pentasaccharide O-glycan from A. baumannii with a longest linear synthetic sequence of 19 steps. This target is particularly relevant due to its role in both fitness and virulence across an apparently broad range of clinically relevant strains. Synthetic challenges include formulating an effective protecting group strategy as well as the installation of a particularly difficult glycosidic linkage between the anomeric position of a 2,3-diacetamido-2,3-dideoxy-D-glucuronic acid and the 4-position of D-galactose.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.