Abstract
A novel iron-catalyzed 1,2-cis-α-amidoglycosylation method to selectively join glycals through α-glycosylation has been developed by the Hao Xu Group, and has proven useful in a synthetic pathway for heparin. To help further optimize the glycosylation reaction, mechanistic studies were conducted on a variety of glycosidic acceptors to better understand why a self cyclized bicyclic acetal side product forms from a secondary glycosidic acceptor, rather than the expected dimerization side product. Mechanistic studies of this bicyclic acetal gave further insight into which glycosidic acceptors may be optimal for the iron-catalyzed glycosylation reaction to produce a greater yield of the desired disaccharide with a 1,2-cis-α-amidoglycosyl linkage. The disaccharide unit is an essential segment involved in forming a heparin chain, so producing the disaccharide in greater yield can translate into a significantly more efficient route for synthesizing the desired heparin product.