SYNTHETIC APPROACHES TO BIOACTIVE CARBOHYDRATES - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 390

12

CHAPTER

SYNTHETIC APPROACHES TO
BIOACTIVE CARBOHYDRATES

XAVIER GUINCHARD, S ´ BASTIEN PICARD, and
DAVID CRICH
Institut de Chimie des Substances Naturelles, Gif-sur-Yvette, France

12.1. INTRODUCTION

With the ever-growing recognition of the importance of oligosaccharides and their
conjugates in biology, and the considerable difficulties in obtaining homogeneous
samples for study fromNature, the chemical synthesis of such molecules has become
one of the most important facets of organic synthesis [1]. With this need has come
the requirement for ever more efficient syntheses and methods with improved and
predictable control of stereochemistry. Indeed, the continued refinement of classical
methods of glycosidic bond formation has been accompanied by the development of
more sophisticated methods such that the synthesis of oligosaccharides containing
as many as 28 saccharide units [2], while still no easy task, may be contemplated.
In this chapter, we present a synthesis of the heparin pentasaccharide, which is a
significant milestone in the area, being the first industrial synthesis of a complex
oligosaccharide for marketing as a pharmaceutical agent. This synthesis may also be
viewed as the apogee of the art of classical oligosaccharide synthesis in that a different
promoter and a method were employed for the formation of each glycosidic bond.
We follow on with the synthesis of an equally complex oligomer, the moenomycin
pentasaccharide, as an illustration of the alternative approach of the application of a
single glycosylationmethod, in this case the sulfoxide method, for the formation of all
glycosidic bonds with the control of stereochemistry achieved through a careful
selection of protecting groups. We then move on to consider some of the more recent
methods for the stereochemical control of challenging glycosidic bonds and their
application as illustrated by a number of different syntheses of bioactive carbohy-
drates. The area of polymer-supported oligosaccharide synthesis is not dealt with as a
separate subject, rather specific examples are interwoven with the text to illustrate
specific points. The synthesis of bioactive oligosaccharides is a vast domain and it is