Synthese von N-Carboranoylamido-Derivaten der Sialinsäure und der Glucose

Abstract

Aim of the work was the development of a highly potent inhibitor of Myelin-associated glycoprotein(MAG)also called siglec-4a protein. MAG inhibits neurite outgrowth from neurons of the injured central nervous system (CNS). Gangliosides with terminal sialic acid (Sia) groups are known in literature as functional binding partners for MAG. The inhibition of this binding by synthetic Sia-derivatives might benefit the regeneration of the injured CNS. Inhibitor was to be synthesized through connection of closo-carboranyl carboxylic acid chloride with the 9-amino-group of 9-amino-5-N-acetylneuraminic acid glycosides. The glucose derivative glucosamine was used as a model compound to study reaction details. The synthesis of the desired N-carboranoylamido derivative of glucose was successful. During the attempt to synthesize an N-carboranoylamido derivative of Sia a degradation of the closo-carborane C2B10-cage to the nido-carborane C2B9-structure was observed. The new synthesized water soluble Sia-derivative nido-carboranoylamido-Neu5Ac2Bn was used in a hapten-inhibition assay. It is a potent inhibitor of soluble Fc-MAG-chimeras.