Thirty five years have elapsed since the gangliosides were first isolated from pathological brain tissue 1). Because of their apparent role in cerebral physiology and their remarkable immunochemical properties, this group of natural substances has become in recent years one of the most attractive topics in lipid research and much progress has been made in the early 1960's. A rapid and dramatic development in the chemistry of the major brain gangliosides which culminated in the complete elucidation of their structure led to the recognition that they have a common basic structure. They are built up from the same tetrasaccharide IV and differ only by the number of sialic acid residues. The establishment of the structure of these complex molecules has opened the way for synthetic studies.
I shall discuss the syntheses of several oligosaccharides which we have recently completed. I have also included a preliminary account of the work on this subject which is presently in progress in our laboratory.
The primary objective of our study in the ganglioside series has been the synthesis of fragments constructed in such a manner as to permit their combination to the tetrasaccharide IV or to the globoside I.
If we split the asialoganglioside I schematically as indicated by the dotted line, we obtain two fragments: the disaccharide galactosyl-(1--*3)-N-acetylgalactosamine (II) and lactosyl ceramide, the well known cytolipin H (fig. ). Both fragments were synthesized earlier in our laboratoryZ-4), and at a first glance it would appear that they could be combined by a glycosidic bond to recover the asialoganglioside. This could be done in principle by the Koenigs-. Knorr reaction, in which the bromide of I! would react with the 4'-OH of Ill, assuming it were possible to protect all other hydroxyl groups. However, although such a combination may be feasible in the living cell, nature has made it difficult for the organic chemist to perform this reaction. The reason is that the hydroxyl group in position 4 of galactose has the axial orientation and is as such completely unreactive.
Let us now consider the fragments which have been obtained by hydrolysis