Concise synthesis of 2,7-anhydrosialic acid derivatives and its application

Abstract

In N-acetylneuraminic acid, apart from O9 and O8, a possible glycosylation site is the O4 position. For example, gangliosides HLG-2 and HPG-7 are considered to be potential lead compounds for carbohydrate-based drug development to treat neural disorders. However, the construction of their alpha(1 -> 4) fucosyl sialic acid and alpha(2 -> 4) linkages between sialic acids is difficult because of the regioselectivity problem. Herein, N-acetyl-2,7-anhydroneuraminic acid was synthesized in three steps from Neu5Ac methyl ester through per-O-trimethylsilylation, heating-assisted intramolecular anomeric protection (iMAP) and desilylation. The iMAP simultaneously circumvents both the 2- and 7-OH protection. Upon protecting the 8- and 9-OH groups as a benzylidene acetal, only 4-OH is free for glycosylation. These 2,7-anhydro-8,9-O-benzylidenesialic acid derivatives were examined as acceptor for an alpha-selective fucosylation to construct the glycosidic linkage of fucosyl alpha(1 -> 4) 2,7-anhydroneuraminic acid. (C) 2017 Published by Elsevier Ltd.