Chapter 3 - Chemical Synthesis of Complex Carbohydrates

Abstract

During the last three decades, carbohydrate synthesis has witnessed tremendous progress, manifested by the enormous number of protecting groups and tactics, glycosylation methodologies, and synthetic strategies developed in the area, as well as the complex structures that have been achieved. Presently there is not a magical strategy that is generally applicable to various oligosaccharides, unlike in oligopeptide and oligonucleotide synthesis. The problems are severalfold. First, the availability of monosaccharide building blocks is still difficult. Although it is currently possible to prepare all kinds of building blocks in the laboratory, it is extremely time-consuming. In fact, for most oligosaccharide syntheses, the largest part of time is spent in the preparation of monosaccharide building blocks. This situation will not change very soon, as it is determined by the structural property of carbohydrates. For example, each amino acid or nucleoside may need only several protecting forms to meet all kinds of synthetic demands, but for a monosaccharide, this number must be one to two orders of magnitudes higher. On top of this, the cost of synthesizing a regioselectively protected monosaccharide is extremely high, which at least presently prohibits the commercialization of complex monosaccharide derivatives. Second, the results of many glycosylation reactions are still difficult to predict. Compared to the chemistry involved in peptide and nucleotide synthesis, glycosylation reactions are much more sensitive to reaction conditions, such as moisture, temperature, the structure of substrates including both donors and acceptors, and solvent.