Glycolipids from Sponges: Isolation, Structure Elucidation, and Synthesis

In recent years, Porifera are showing to be one of the richest source of new glycolipids. Many glycolipids from marine sponges, even though belonging to the wide class of glycosphingolipids (GSLs), have unusual structure, such as the immunostimulating alpha-galactosyl-GSLs from Agelas species or the immunosuppressive plakoside A and B from Plakortis simplex. In addition, marine sponges contain a number of atypical glycolipids, without counterpart among glycolipids from other phyla. For example, simplexides are glycosides of a very-long-chain secondary alcohol, whereas plaxyloside possesses a linear polyisoprenoid aglycon and a carbohydrate chain composed of six linearly arranged xylopyranose units. The systematic study of glycolipids from sponges is far from being terminated, and many new compounds are currently under investigation. The first part of the communication will cover our most recent results in this field. A study of the immunostimulating activity of alpha-galactosyl-GSLs from Agelas species, that is related to their antitumor activity, suggested the hydroxyl group at position 2 of the inner galactose to be crucial for the activity of these compounds. Therefore, we decided to synthesize analogues of natural alpha-galactosyl-GSLs, modified at this position. Our first target was 1-O-(2-deoxy-alpha-D-galactopyranosyl)-2-docosanoylamino-1,3,4-octadecanetriol. The second part of the communication will describe an efficient strategy to the total synthesis of 2-deoxy-alpha-glycosylceramides, using galactal as chiral starting material for both the sphingosine and the sugar units. The biological activity of these derivatives was evaluated in collaboration with Sigma-Tau S.p.A., Italy. In addition, this synthetic work led to the discover of some interesting new aspect of carbohydrate chemistry, that will also be discussed.