A New Reactivity-Based One-Pot Synthesis of N-Acetyllactosamine Oligomers

Poly- N-acetyllactosamine oligomer is a type-2 glycan core from which a number of important bioactive glycoconjugates are assembled in vivo. Development of an effective synthesis of N-acetyllactosamine oligomers will therefore provide a new chemoenzymatic entry to this class of complex saccharides. This paper describes the design and synthesis of thioglycoside building blocks, determination of their relative reactivity values, and demonstration of their use in the programmable one-pot synthesis of various N-acetyllactosamine oligomers. Through a combination of segment condensation, the strategy allows for the preparation of larger oligosaccharides with minimal protecting group manipulation, as illustrated in the synthesis of an octasaccharide in a very short period of time.