Poly-amido-saccharides: Synthesis via Anionic Polymerization of a β‑Lactam Sugar Monomer

Enantiopure poly-amido-saccharides (PASs) with a defined
molecular
weight and narrow dispersity are synthesized using an anionic ring-opening
polymerization of a β-lactam sugar monomer. The PASs have a
previously unreported main chain structure that is composed of pyranose
rings linked through the 1- and 2-positions by an amide with α-stereochemistry.
The monomer is synthesized in one-step from benzyl-protected d-glucal and polymerized using mild reaction conditions to give degrees
of polymerization ranging from 25 to >120 in high yield. Computational
modeling reveals how the monomer’s structure and steric bulk
affect the thermodynamics and kinetics of polymerization. Protected
and deprotected polymers and model compounds are characterized using
a variety of methods (NMR, GPC, IR, DLS, etc.). On the basis of circular
dichroism, the deprotected polymer possesses a regular secondary structure
in aqueous solution, which agrees favorably with the prediction of
a helical structure using molecular modeling. Furthermore, we provide
evidence suggesting that the polymers bind the lectin concanavalin
A at the same site as natural carbohydrates, showing the potential
of these polymers to mimic natural polysaccharides. PASs offer the
advantages associated with synthetic polymers, such as greater control
over structure and derivitization. At the same time, they preserve
many of the structural features of natural polysaccharides, such as
a stereochemically regular, rigid pyranose backbone, that make natural
carbohydrate polymers important materials both for their unique properties
and useful applications.