Recent Advances in Chemical Synthesis of Polysaccharides

Abstract

Polysaccharides are a class of bio-macromolecules with highly complex structures that are widely found in living organisms such as microorganisms, plants and animals. Polysaccharides serve not only as structural components and energy sources of cells, but also as important signaling molecules which are involved in many key biological processes. Studies on polysaccharide-mediated biological processes require access to structurally defined molecules, which approach the size and complexity of those found in nature, but naturally-occurring polysaccharides usually exist in microheterogeneous forms, making it difficult or even impossible to isolate pure polysaccharides from natural sources in most cases. Chemical synthesis represents a reliable solution to this problem, which can provide polysaccharide samples with defined chemical structures for functional studies and even a library of analogs of natural glycans for structure-activity relationship investigations. But unlike oligonucleotides and peptides, which can already be obtained by automated synthesizers in a very short of time, the chemical synthesis of glycans remains a great challenge for synthetic chemists. The major challenge for glycan synthesis lies in the need to handle both stereo-and regio-chemistry in the construction of each glycosyl linkage, and the extensive protecting-group manipulations as well as much intermediate separation make it a tedious and time-consuming process. Over the past decades, carbohydrate chemists have developed many glycosylation reactions. A series of strategies for glycan assembly have been also established. The advances in both synthetic methods and strategies have significantly increased the synthetic efficiency of carbohydrate molecules, and many great accomplishments in the field of polysaccharide synthesis have been witnessed in recent decades. Some representative methods and strategies, and their successful applications in the chemical synthesis of complex polysaccharides are summarized in this review.